cross coupling reactions catalyzed by iron group metals

69-1111_Hatakeyama.indd1 Introduction
N Heterocyclic carbenes (NHCs) were rst independently synthesized by Wanzlick and Öfele in 1968. 1 After two decades, Arduengo et al. succeeded in the isolation of a stable NHC, 1,3 di(1 adamantyl)imidazol 2 ylidene (IAd). 2 Since then, numerous NHCs and their precursors have been prepared 3 and applied to various transition metal catalyzed reactions as a new class of auxiliary ligands. A variety of late transition metal complexes possessing NHC ligands have been isolated and have proven to be effective catalysts in a variety of synthetic organic reactions. 4 One of the most important examples is the ruthenium/NHC catalyst for olen metathesis developed by Grubbs et al., 5 for which the Nobel Prize was awarded in 2005. Replacement of one of the two tricyclohexylphosphine ligands in the rst generation Grubbs catalyst with 1,3 di(1 mesityl)imidazolin 2 ylidene (SIMes) affords the second generation Grubbs catalyst, which has signicantly improved stability and reactivity. Recently, the remarkable potential of NHC ligands was demonstrated in several palladium catalyzed cross coupling and related reactions, for which the Nobel Prize was awarded in 2010, just one year ago of this report. 6 Bulky NHC ligands, such as (S)IMes and (S)IPr, were shown to signicantly improve the performance of the Pd catalyst compared to traditional phosphine ligands. The catalytic improvements derived from the NHC type ligands are often attributed to their strong σ electron donating properties, 7 which result in strong NHC metal bonds and prevent catalyst
decomposition. The application of NHC ligands in iron group metal
(IGM) catalysis has attracted considerable attention from aca- demia and industry due to their practical advantages as well as unique reactivity. Since the pioneering work of Herrmann on the nickel NHC catalyzed, Kumada Tamao Corriu coupling reaction, 8 the use of NHC ligands in IGM catalyzed reactions have been actively pursued. 9 The successes of these catalysts is attributable to their strong σ electron donating properties and bulkiness, 7,10 both of which lead to in situ formation of coordinatively unsaturated reactive species to achieve high catalytic performance. In this report, we describe our recent efforts to achieve selective C sp 2 C sp 2 cross coupling reactions based on IGM/NHC catalyst systems, which yielded new cross coupling reactions with nonconventional reaction mechanisms.
2 Selective Biaryl Cross Coupling Catalyzed by Iron, Cobalt, and Nickel Fluorides with the Assistance of NHC Ligands
2.1 Background Since functional biaryls constitute a diverse array of func-
tional materials, such as optoelectronics, drugs and agrochemi- cals and their intermediates, 11 considerable effort has been devoted to developing efcient and selective methods for biaryl synthesis. 12,13 Reductive homocoupling of aryl halides or pseudohalides, i.e., the classical Ullmann reaction, has been developed to give the desired symmetrical biaryls by using various transition metals. 12a,c Palladium catalysts in combination with
Cross Coupling Reactions Catalyzed by Iron Group Metals and N Heterocyclic Carbenes
via Nonconventional Reaction Mechanisms
International Research Center for Elements Science, Institute for Chemical Research, Kyoto University Uji, Kyoto, 611 0011, Japan
(Received September 20, 2011; E mail: [email protected])
Abstract: New cross coupling reactions catalyzed by iron or iron group metals (IGMs), consisting of Fe, Co, and Ni with N heterocyclic carbenes (NHCs), are described in this report. Highly selective biaryl cross coupling reactions between aryl halides and aryl Grignard reagents were achieved by using a combination of uoride salts of IGMs and NHCs. In the course of the study, an unexpected alkenylative cross coupling between alkyl aryl suldes and aryl Grignard reagents was found, in which a typical Ni/NHC catalyst displayed unprecedented reactivity toward sulde substrates. Theoretical studies suggest that the biaryl coupling and the alkenylative coupling reactions proceed via two nonconventional mechanisms, which are substantially different from the widely accepted cross coupling mechanism: In the biaryl cross coupling, treatment of the catalyst mixtures of IGM uorides and NHCs with an excess amount of the aryl Grignard reagent results in the generation of organometalate complexes, [Ar 1M IIF 2]MgBr (MFe, Co, and Ni). These organometalate species undergo oxidative addition of aryl halide substrates to form intermediates in a high oxidation state (most likely a+IV state) possessing two different aryl groups, Ar 1Ar 2M IVF 2. The heteroleptic diaryl organometallic intermediates collapse easily to afford unsymmetrical biaryls in a highly selective manner. On the other hand, the alkenylative coupling reaction using a Ni/NHC catalyst involves formation of a low oxidation state Ni(0) thioaldehyde complex, which is transformed to an alkenylnickel species via α deprotonation of the thioaldehyde and subsequent C S bond cleavage of the resulting enethiolate intermediate. The alkenylnickel species undergoes transmetalation with an aryl Grignard reagent to form alkenyl/aryl coupling products via reductive elimination. The present cross coupling reactions catalyzed by IGMs with NHC ligands provide highly selective C sp 2 C sp 2 coupling methods for the synthesis of unsymmetrical biaryls and styrene derivatives, offering an opportunity to gain new mechanistic insights into IGM catalyzed cross coupling reactions.
88 J. Synth. Org. Chem., Jpn.1282
69-1111_Hatakeyama.indd 88 2011/10/20 14:24:44
an appropriate terminal reductant such as zinc are currently of preferred choice. 12b Furthermore, the cross coupling of two different aryl halides under reducing conditions was developed. 14 The biaryl synthesis under oxidative conditions has been an alternative since the seminal work of Kharasch and coworkers, who discovered that aryl Grignard reagents undergo efcient homocoupling in the presence of catalytic amounts of rst row transition metal salts, such as the metal halides of chromium, manganese, iron, cobalt, nickel, and copper. 15 Recent progress in oxidative coupling chemistry extended its utility to the synthesis of various functionalized biaryls. 16 Notwithstanding the advancements in both reductive and oxidative biaryl coupling reactions, the use of transition metal catalyzed cross coupling reactions is preferred because they offer synthetic advantages such as high selectivity, broad substrate scope, and mild reaction conditions. 17 In fact, a wide range of arylmetal compounds has been successfully used as the nucleophilic partner in unsymmetrical biaryl coupling reactions (Scheme 1). While various organometallic compounds such as aryllithium, 18 magnesium, 19 boron, 20 silicon, 21 copper, 22 zinc, 23 or tin compounds 24 have been used in the biaryl coupling reactions, aryl Grignard reagent is likely ideal for practical synthesis because of their availability, cost performance, and environmental innocency. Despite the synthetic advantages of Grignard reagents, there is one serious draw- back, the unwanted formation of the symmetrical biaryls via undesired homocouplings of the Grignard reagents and/or the aryl electrophiles.
Our research group has been interested in the development of iron catalyzed reactions, 25 27 and engaged in the development of selective iron catalysis to overcome the aforementioned homocoupling limitation. During the course of the study, it was found that the combination of iron uoride and NHC ligands resulted in a highly selective and practical catalyst for the biaryl cross coupling of aryl Grignard reagents. 28 Although metal uorides are known to display unique reactivity and selectivity in transition metal catalyzed carbon carbon bond forming reactions, 29 and the “uoride effect” has attracted considerable interest in synthetic chemistry, 30 their reactivity has remained unstudied in transition metal catalyzed cross coupling reactions. 31,32 Therefore, we reported the careful investigation of the “uoride effect” in cobalt 33 and nickel catalyzed 34 cross coupling reactions to achieve selective biaryl cross coupling of aryl halides with arylmagnesium compounds. The full account of the synthetically useful unsymmetrical biaryl coupling with the novel IGM uorides/ NHC ligand catalysts is presented in this chapter. 35
2.2 Iron Fluoride/SIPr Catalyzed Biaryl Cross Coupling The investigation was initially focused on iron based cata-
lysts because there is no established practical method for Fe catalyzed biaryl cross coupling reactions. 25 28 While efcient
homocoupling reactions of arylmagnesium compounds using Fe catalysts have been reported, 16a,b,donly a few were published in the same timeframe as our study. 36,37 We began by conduct- ing a careful and detailed catalyst screening for the reaction of a simple aryl chloride with an arylmagnesium reagent (Scheme 2). The benchmark coupling reaction was performed by heating a THF solution of chlorobenzene 1, p tolylmagnesium bromide (p TolMgBr, 2.5 equiv), iron salt (5 mol%), and an additive, at 60 for 24 h (Table 1, entry 1). Various additives, including imidazolium and imidazolinium salts (as shown in Figure 1), as well as typical phosphine ligands were studied in combination with a catalytic amount of various iron uoride precursors.
An optimum yield of 98% for 4 methylbiphenyl 2 was achieved by using 5 mol% of FeF 3·3H 2O and 15 mol% of SIPr·HCl (entry 1). The undesired homocoupling reaction occurred sluggishly and gave a negligible amount of biphenyl 3 and a small amount of 4,4’ dimethylbiphenyl 4 (0.018 mmol, 4% yield, based on the amount of p TolMgBr). As shown in entry 2, when the less sterically demanding NHC was used, a lower conversion of the starting chlorobenzene 1 was observed. The unsaturated NHC precursors, IPr·HCl and I t Bu·HCl, were ineffective (entries 3 and 5). The counter anion of the NHC precursors displayed considerable inuence on the reactivity (entry 4). The use of 10 or 5 mol% of SIPr·HCl resulted in a selective, but lower conversion (entries 6 and 7). The reaction was sluggish without an NHC precursor (entry 8). As shown in entry 9, N,N,N ’,N ’ tetramethylethylenediamine (TMEDA), one of the most effective additives for the iron catalyzed cross coupling of aryl Grignard reagents and non activated alkyl halide, did not promote the reaction.
A remarkable contrast in the reactivity of various iron precursors is shown in entries 10 17. FeF 2·4H 2O showed a comparable catalytic activity to FeF 3·3H 2O and afforded 2 in 96% yield. In the presence of a catalytic amount of anhydrous FeF 3 or FeF 2, the reactions proceeded selectively but did not reach completion probably owing to their lower solubility in THF (entries 11 and 12). Note that the addition of 15 mol% of water to FeF 3 resulted in only a limited increase in the product yield (entry 13). It was assumed that water or hydroxide might react with the solid surface of FeF 3 and make it partially solu- ble, thereby promoting the generation of the catalytically active species. 38 A mixture of anhydrous FeF 3 and SIPr·HCl (1:2 ratio) was nely ground in inert atmosphere and this mixture showed comparable reactivity to the FeF 3·3H 2O/SIPr·HCl system. The use of FeCl 3 or Fe(acac) 3 as an iron source resulted in predominant homocoupling with or without SIPr·HCl (entries 14 16). Pretreatment of FeCl 3 with KF also generated a catalytically active species, which gave the unsymmetrical biaryl with the same efciency as that afforded by the hydrates of iron uorides (entry 17). The experiments indicate that the involvement of H 2O or metal hydroxide in the catalytic C C bond forming process is very unlikely.
The procedure described above required a large excess of
Scheme 1. Metal catalyzed unsymmetrical biaryl coupling.
Scheme 2. Iron catalyzed cross coupling between PhCl and p TolMgBr.
Vol.69 No.11 2011 89 1283
69-1111_Hatakeyama.indd 89 2011/10/20 14:24:47
aryl Grignard reagent to generate the catalytically active iron species, which prompted us to investigate various organometallic reagents for use as iron based catalyst activators (Scheme 3). 39 For example, the cross coupling between chlorobenzene 1 and p TolMgBr using reduced amounts of iron u- oride and Grignard reagent (3 mol% and 1.5 equiv, respectively) did not complete, and gave the cross coupling product in only 72% yield after 24 h at 60 (Table 2, entry 1). Instead of a large aryl Grignard reagent excess, MeMgBr and EtMgBr were found to activate the catalyst precursors, suggesting that insufcient basicity of the aryl Grignard reagent towards deprotonation of the NHC precursors as well as the reaction with hydrates of iron uorides resulted in slow substrate conversion. The treatment of FeF 3·3H 2O and SIPr·HCl with 18 mol% of MeMgBr to quench all protons derived from catalyst precursors enhanced the reaction rate to give 2 in 97% yield with 1% recovery of 1 (entry 2). Additional MeMgBr slightly enhanced the reaction rate (entry 3). With EtMgBr (18 mol%), the reaction reached completion in 12 h to give 98% yield using 1.2 equivalents of p TolMgBr (entry 4). When 27 mol% of EtMgBr was used, ethylbenzene was produced in 3% yield via cross coupling of the residual EtMgBr and 1 (entry 5). The lower yield of the homocoupling product 4 (2%) suggests that some EtMgBr is consumed for the partial reduc-
tion of the iron(III). 40 Therefore, we propose that EtMgBr is sufciently basic to react with the water molecules of the metal uoride hydrates in order to assist in their dissolution.
Table 3 summarizes the scope of this iron catalyzed biaryl cross coupling reaction under the optimal conditions and the procedures shown in Scheme 3. The coupling reaction depends strongly on the nature of the leaving group, where chlorobenzene gave 2 selectively in 98% yield as described above, bromo and iodobenzene produced larger amounts of the homocoupling byproduct 4 than the desired product 2 (entry 1 vs. entries 2 and 3). Phenyl triate showed lower reactivity, giving 27% yield of 2 (entry 4). Fluorobenzene did not react under the reaction conditions (entry 5). 4 Chloroanisole reacted with p TolMgBr to give the desired product in 92% yield (entry 6). Fluorinated biaryls, possessing a representative mesogen structure of liquid crystal molecules, were obtained in good yields (entries 7 and 8). Though the reactions of o tolyl and mesitylmagnesium bromide were rather sluggish under standard conditions, the corresponding biaryl coupling products were obtained in 90 and 93% yields, respectively, at elevated reaction temperatures (entries 9 and 10). 4 Fluorophenylmagnesium bromide also reacted smoothly to give the desired product in 87% yield (entry 11). 1 and 2 naphthylmagnesium bromide participated in the reaction (entries 12 and 13). The dimethylamino and methylthio groups did not interfere in the coupling reaction (entries 14 and 15). Note that a small amount of 4,4’’ dimethyl 1,1’’;4’,1’’terphenyl (4%), formed via cleavage of the Ar SMe bond (via 1:2 cross coupling), which is often observed in the nickel catalyzed coupling reactions. 41 An acetal remained intact under these reaction conditions (entry 16). 2 Chloroquinoline and 2 bromopyridine took part in the selective biaryl coupling (entries 17 and 18).
Table 2. Activation of precatalysts by using MeMgBr and EtMgBr.
Figure 1. NHC precursors.
Table 1. Screening of iron salts and additives in the cross coupling of chlorobenzene with p tolylmagnesium bromide.
Scheme 3. Activation of iron uoride/SIPr by using EtMgBr.
69-1111_Hatakeyama.indd 90 2011/10/20 14:24:54
2.3 Cobalt and Nickel Fluorides/IPr Catalyzed Biaryl Cross Coupling
Cobalt and nickel catalysts were examined using the present uoride/NHC strategy. Although numerous C C bond forming reactions based on cobalt 42 and nickel 43 catalysts have been studied, the corresponding metal uorides have been only sporadically studied in the cross coupling eld. 44 The reaction of chlorobenzene 1 with p TolMgBr in the presence of catalytic amounts of cobalt and nickel uorides with various NHCs was investigated as shown in Scheme 4, comrming that a similar “uoride effect” works in IGMs and is useful for the selective biaryl synthesis.
Table 4 summarizes the results of the Co and Ni cata-
lyzed reactions. The reaction with CoF 2·4H 2O (3 mol%) and IPr·HCl (6 mol%) selectively produced the cross coupling product 2 in 95% yield along with small amounts of homocoupling products 3 and 4 (3% and 11% yields, respectively, entry 1). Alternatively, the reaction with CoCl 2·6H 2O gave 2 in a considerably lower yield (68%) with increased formation of byproducts 3 and 4 (26% yield in total, entry 2). SIPr·HCl was less effective than IPr·HCl (entry 3). The reaction with NiF 2or NiF 2·4H 2O (1 mol%) and IPr·HCl (2 mol%) gave 2 selectively, but the use of NiCl 2 resulted in less selectivity (entries 4 6). With a reduced amount of NiF 2 (0.5 mol%), the reaction proceeded to completion after 48 h, affording 2 in 98% yield (entry 7). In contrast to the iron catalyst, the counter anion of the NHC precursors did not affect the product yield (entry 8). Decreasing the steric bulkiness of the N aryl substituent led to a decrease in product yield (entries 9 and 10). SIPr·HCl was slightly less effective than IPr·HCl (entry 11). It is noteworthy that addition of KF to NiCl 2 improved the cross/homo selectivity in the reaction of bromobenzene with p TolMgBr (entries 12 and 13). From these results, we chose SIPr·HCl for iron uoride and IPr·HCl for cobalt and nickel uorides as the standard NHC ligands in the subsequent investigations.
Since the seminal work reported by Kumada and Tamao, 34b,c,45 phosphine ligands such as the chelating 1,2 bis(diphenylphosphino)ethane (DPPE) ligand have been effectively used in cross coupling reactions with nickel and palladium catalysts. Therefore, DPPE and NHC ligands in the nickel or cobalt uoride catalyzed biaryl cross coupling reactions were compared (Table 5). Interestingly, the bisphosphine ligand did not promote the reaction at all when IGM uorides were used as the pre catalyst (entries 1, 2, and 3). Elongation of the reaction period as well as higher reaction temperature did not enhance the reaction and bromobenzene was recovered almost quantitatively. In stark contrast, NHC ligands promoted the cross coupling reaction effectively to
Table 4. Screening of cobalt and nickel salts with various NHC ligands.
Table 3. Iron uoride/NHC catalyzed cross coupling of aryl halides with aryl Grignard reagents.
Scheme 4. Cobalt and nickel catalyzed cross coupling between PhCl and p TolMgBr.
Vol.69 No.11 2011 91 1285
69-1111_Hatakeyama.indd 91 2011/10/20 14:25:04
give the desired biaryl in almost quantitative yield (entries 4 6). As shown in entry 7, when a nickel chloride was used as the pre catalyst, the biaryl coupling reaction took place in the presence of a bisphosphine ligand; however, the selectivity was not as high as that in the reaction with IPr (entry 6) under the same reaction conditions.
2.4 Scope of Cobalt and Nickel Fluorides/IPr Catalyzed Biaryl Cross Coupling: Comparisons with Iron Fluoride/ SIPr Catalyst
Under optimized conditions, uoro , bromo , and iodo- benzenes were examined as electrophiles to determine the scope of the leaving group in the present reactions (Table 6). Reactions with p TolMgBr (1.2 equiv) were carried out at 60 in the presence of FeF 3·3H 2O and SIPr·HCl (3 and 9 mol%, respectively), NiF 2 and IPr·HCl (0.5 and 1 mol%, respectively), or CoF 2·4H 2O and IPr·HCl (0.5 and 1 mol%, respectively).
Fluorobenzene was fully inert under these conditions (entry 1). While the reaction of chlorobenzene with the iron catalyst selectively afforded the cross coupling product 2, that of bromobenzene and iodobenzene generated considerable amounts of homocoupling product 4 (entries 2 4). As shown in entries 5 7, the cobalt catalyst was found effective for the reaction with both of chlorobenzene and bromobenzene, albeit ineffective for that with iodobenzene. The nickel catalyst showed the broadest scope on the halide substrate and was found more effective than the iron and cobalt catalyst in terms of catalytic activity and selectivity (entries 8 10).
The IGM uoride/NHC catalyzed cross coupling reaction is widely applicable to a broad range of substrates. Table 7 summarizes the scope of the reactions, which were carried out according to the procedure described above. Electron rich 4 chloroanisole reacted smoothly with p TolMgBr to give the desired product in 92%, 94%, and 88% yields, respectively (entry 1). Fluorine substituted biaryls, the representative mesogen structure of liquid crystal molecules, can be synthesized using 1 chloro 4 uorobenzene, 1 chloro 3,4 diuorobenzene, and 1 bromo 3,5 diuorobenzene in medium to high yields with proper choice of metal catalyst (entries 2 4 and 12). In the case of 1 chloro 3,4 diuorobenzene, the iron and cobalt catalysts gave high yields of the desired product,
but the nickel catalyst gave a much lower yield with considerable generation of the deuorinated biaryl and teraryl compounds, via C F bond cleavage. A similar trend was observed in the reaction with electron decient 4 uorophenylmagne- sium bromide. While the reactions of o tolyl and mesitylmagnesium bromides were rather slow because of their steric bulkiness, elevated reaction temperatures (80 and 120 ) gave the corresponding products in medium to high yields (entries 5, 6, and 13). In these cases, the nickel catalyst showed higher catalytic activity than the other catalysts. 1 and 2 naphthylmagnesium bromides took part in the iron catalyzed coupling reaction (92% and 96% yields, respectively, entries 7 and 8). The reactions of 2 naphthylmagnesium bromide with the cobalt and nickel catalysts were less selective, giving 70% and 82% yields of the desired product and 24% and 17% of 2,2’ binaphthyl, respectively. As shown in entry 9, the dimethylamino group seems to interfere with the nickel catalyzed coupling reaction, but not the iron catalyzed coupling. Acetal functionality remained intact under the reaction conditions (entry 10). In the presence of the iron catalyst, the reaction of 4 chlorothioanisole with p TolMgBr took place via a selective C Cl bond cleavage to give 4 methyl 4’ methylsulfanylbiphe- nyl in 80% yield. The cobalt and nickel catalyzed reactions were less selective and afforded 55% and 10% yields with considerable amounts of side products such as 4,4’’ dimethyl 1,1’:4’,1’’ terphenyl via C S bond cleavage. 46 As shown in entry 12, 1 bromo 3,5 diuorobenzene selectively gave the desired product in the presence of the nickel catalyst owing to the considerably higher reactivity of the C Br bond as compared to the C F bond. The iron and cobalt catalysts gave 4,4’ dimethylbiphenyl as the major product via the homocoupling of p TolMgBr (35% and 46%, respectively). Whereas the reaction of 1 bromo 2 (but 3 enyl)benzene and p TolMgBr with the nickel catalyst selectively gave the desired product, the reaction with the iron catalyst gave only 18% yield with 68% yield of 4,4’ dimethylbiphenyl via a homocoupling reaction (entry 14).
Heteroaromatic nucleophiles, as well as electrophiles, took part in the selective biaryl cross coupling reaction (entries 15 20). In the presence of cobalt and nickel catalysts, 2 bromo-
Table 5. Comparison between bisphosphine and NHC ligands in IGM uorides/phosphine catalyed biaryl crosscoupling.
Table 6. Leaving group capabilities of IGM uorides/NHCs.
69-1111_Hatakeyama.indd 92 2011/10/20 14:25:06
pyridine reacted with p TolMgBr at 60 producing the desired product in 95% and 93% yields, respectively (entry 15). The reaction with the iron catalyst was less selective, yielding 66% of the desired product and 30% of 4,4’ dimethylbiphenyl
via the homocoupling of p TolMgBr. In these cases, 2 bromopyridine was not recovered. As shown in entry 16, the reaction between 3 bromopyridine and p TolMgBr took place selectively with the nickel catalyst but not with the iron or cobalt
Table 7. Substrate scope of iron group metal uoride/NHC catalyzed baryl crosscoupling reactions.
Vol.69 No.11 2011 93 1287
69-1111_Hatakeyama.indd 93 2011/10/20 14:25:14
catalysts. The reaction between 2 chlorothiophene and p anisylmagnesium bromide was selective with the cobalt catalyst to give the desired product in 95% yield (entry 17). In the presence of the iron or nickel catalyst, the reaction did not proceed to completion, and 2 chlorothiophene was recovered (ca. 90% and 50%, respectively). 3 Bromothiophene gave the corresponding coupling product in good yields in the presence of the cobalt and nickel catalysts (entry 18). The reaction of 2 chloroquinoline with mesitylmagnesium bromide at 100 yielded the desired product (82%, entry 19). In the presence of the cobalt and nickel catalysts, the reaction of 2 bromopyridine with 2 thienylmagnesium bromide proceeded to completion at 80 to give 2 thiophen 2 yl pyridine in 99% yield (entry 20). 2.5 Mechanistic Consideration of the Catalytic “Fluoride
Effect”: Proposal of New Mechanisms and Theoretical Evaluation
To gain mechanistic insight into the origin of the high cross/homo selectivity of the metal uoride catalysts, a series of control experiments and theoretical studies were conducted. The results of the control experiments using a variety of metal salts, NHC ligand precursors (SIPr·HCl or IPr·HCl), and p TolMgBr are summarized in Scheme 5 and Table 8. The reactions were carried out in the absence of an aryl halide, which has been reported to accelerate the reductive elimination of neutral organonickel compounds. 47 A stark difference between the metal chloride and uoride reactivity towards the Grignard reagent was observed. As shown in Scheme 5, treatment of FeCl 2 (0.1 mmol) with p TolMgBr (20 equiv) at 0 in the presence of SIPr·HCl (3.0 equiv) produced 0.096 mmol of 4,4’ dimethylbiphenyl 4 (96% yield based on the amount of FeCl 2). Similarly, treatment of FeCl 3 with p TolMgBr under the same conditions resulted in 1.5 times the stoichiometric amount of 4 as compared to FeCl 2 treated with the Grignard reagent. The results clearly indicate that p TolMgBr reduces the metal chlorides to give the corresponding metal(0) species and the biaryl product simultaneously, which corresponds to the initial activation step in the cross coupling reaction. Alter- natively, iron (II or III) uorides did not afford 4 under the same conditions. Only a small amount of 4 was formed at 60 (with FeF 2 and FeF 3 in 6% and 11% yields, respectively), while the biaryl cross coupling reaction proceeded smoothly at the same temperature in the presence of an aryl halide. Table 8 summarizes the results of similar control experiments for the cobalt and nickel halides. Treatment of cobalt and nickel chlorides with p TolMgBr resulted in the rapid homocoupling of the Grignard reagents (0 , 1 h) to give 4 in quantitative yield (entries 3 and 4). However, the corresponding uorides of these metals did not react with the Grignard reagent under the same conditions resulting in an 8 11% yield of 4 at 60 .
The thermal instability of homoleptic tetraphenylferrate species, such as [Ph 4Fe]Li 2,
48 resulted in the assumption that the homoleptic metalate complex via the transmetalation and addition of an arylmagnesium reagent was dominant in the reaction of the metal chlorides. Conversely, the sharp contrast observed in the reactivity of metal uorides (no signicant biaryl formation) suggests that the uoride counter ion may interfere with the formation of the fully arylated metalate complex presumably due to its high electronegativity and strong uoride coordination to the IGM center.
It should be noted that chlorobenzene 1 did not react in the presence of a stoichiometric amount of IGM uorides and slight excess of NHC ligands. 95 99% of the starting material was recovered without the formation of any byproduct after 24 h at 60 . The low reactivity provides evidence that oxidative addition of the aryl halide to the divalent metal uorides does not occur in the absence of Grignard reagent, even in the presence of NHC ligands (not the NHC precursors). The generation of reactive intermediates requires the reaction of corresponding metal uorides with an aryl Grignard reagent.
Based on the control experiments described above and the previously suggested reaction mechanisms involving the organometalate complexes of iron, 26o cobalt, 49 and nickel 50 in cross coupling reactions, two catalytic cycles are proposed in Figures 2 and 3. Figure 2 depicts a metalate mechanism, which starts with the formation of heteroleptic metalate(II) complex A from the divalent metal uoride and arylmagnesium reagent (Ar 1MgX). Complex A undergoes oxidative addition with an aryl halide to give elusive higher valent (formally IV oxidation state) species B carrying Ar 1 and Ar 2. 51 Subsequent reductive elimination to give the unsymmetrical biaryl (Ar 1 Ar 2) gener- ates metal(II) complex C bearing two uorides and one halo- gen ligand derived from Ar 2X on the metal center. The reaction of C with Ar 1MgX regenerates reactive intermediate A. A radi- cal type (II) (III) mechanism has been reported for iron catalyzed cross coupling reactions of alkyl halides with arylmagnesium reagents. 52 The catalytic cycle depicted on the left hand side of Figure 3 shows a canonical “(0) (II) mechanism,” which consists of the oxidative addition of an aryl halide to metal(0) intermediate D, transmetalation between arylmetal halide E and Ar 1MgX, and reductive elimination of Ar 1 Ar 2 from diarylmetal(II) F. 53 We believe that the present reaction based on the metal uoride catalyst does not take place via the popular (0) (II) mechanism, but more likely via the higher valent metalate mechanism, which is analogous to those of cuprate mediated substitution reactions and catalytic cross coupling reactions. 54 The nal reductive elimination process in
Scheme 5. Homocoupling of p TolMgBr by IGM halides.
Table 8. Comparison between IGM chlorides and uorides in the homocoupling of p TolMgBr.
69-1111_Hatakeyama.indd 94 2011/10/20 14:25:17
the metalate mechanism is presumed to be much faster than that of the “(0) (II) mechanism” owing to instability of high valent intermediate B, thereby, prevailing over the undesirable transmetalation or formation of ate complexes carrying excess aryl groups (such as Ar 1 2Ar 2M, G). 55
We employed DFT calculations to evaluate the aforementioned reaction pathways in the proposed mechanism starting from a metalate(II) complex. A chemical model consisting of PhMgCl and PhCl as the nucleophilic and electrophilic coun- terparts, NiF 2 as the metal catalyst, and 1,3 dimethylimidazol 2 ylidene (IMe) as the auxiliary ligand was adopted (Figure 4). The widely used B3LYP/6 31G DFT method was employed for the mechanistic studies of the formation of nickel catalyzed C C bonds. 56
The localization of a single reaction pathway that consists of the formation of a σ complex, the oxidative addition of chlorobenzene (Ph Cl), and the subsequent reductive elimination of the biphenyl (Ph Ph) was successful. The energy prole
and structural information for the equilibrium and transition structures are shown in Figure 5. The nickelate complex (SM1) interacts with chlorobenzene to form the σ complex (CP1), which is 9.7 kcal/mol higher in energy than the sum of the electron energies of SM1 and Ph Cl. The uphill energetics are presumably due to the instability caused by the distortion in the CP1 square pyramidal structure (angles: F 1 Ni F 276.3°, Cl Ni F 275.0°, Cl Ni C 1175.4°). The bond lengths indicate a weak electrostatic interaction between the nickel center and the lone pair of electrons in the chloride ligand (Ni Cl2.69, C 2 Cl1.77, cf. C Cl of Ph Cl1.76). The oxidative addition of Ph Cl via TS1 (C 2 Cl2.12, Ni C 2
2.11, Ni Cl2.31) requires an activation energy of 18.3 kcal/mol to form octahedral Ni(IV) intermediate CP2 (Ni C 21.95, Ni Cl2.35). This process is endothermic (+6.2 kcal/mol), reecting the elusive nature of tetravalent organonickel species. The reductive elimination of Ph Ph from CP2 occurs via TS2 with a small activation energy of +3.5 kcal/mol to form square planar Ni(II) complex PD1 with a calculated stabilization energy of 49.4 kcal/mol. In light of the low activation barrier, it is expected that the tetravalent nickel intermediate would not be a stationary point when the NHC ligand has sterically demanding aryl groups on the nitro- gen atoms as in the real system.
The same DFT calculations on the iron and cobalt uoride/NHC systems were performed using similar chemical models. The difculty in the treatment of multiple spin state systems of these metals (a divalent iron can take S0, 1, and 2 spin states, and a divalent cobalt can take S1/2 and 3/2 spin states) has been well documented for the DFT method, 57 resulting in computational evaluation of the most critical step of the above presented metalate mechanism, which is oxidative addition. The equilibrium structures of the starting complexes (SM1), the high valent oxidative addition product (CP2), and the transition structures that connect SM1 and CP2 were optimized. The energies associated with the chlorobenzene oxidative addition to heteroleptic metalate complexes SM1 Fe and SM1 Co, were obtained as shown in Figures 6 and 7, respectively. For the iron system, the reaction coordinates of the quintet state (S2) and the triplet state (S1) were isolated, but the singlet state (S0) was unsuccessful. As shown in Figure 6, the oxidative addition of PhCl to ferrate complex SM1 Fe q in the quintet state took place via TS1 Fe q with a reasonable activation barrier (ΔE ‡+29.5 kcal/mol) to give tetravalent intermediate CP2 Fe q. In the reaction coordinate of the triplet state (shown with a dashed line in Figure 6), it was found that tetravalent intermediate CP2 Fe t is slightly more stable than the one in the quintet state (CP2 Fe qΔΔE t q -5.5 kcal/mol), whereas the other stationary points (SM1 Fe t and TS1 Fe t) have higher energies than those in the quintet state. Based on these results, it was assumed that the most stable SM1 Fe q was the likeliest candidate for the reactive intermediate toward the oxidative addition. This suggests that the cross coupling reaction should proceed in the quintet state to tentatively form the elusive iron(IV) intermediates, which may be prone to rapid reductive elimination to give the cross coupling product (Ph 1 Ph 2). The spin cross over from CP2 Fe q to CP2 Fe t may be possible but has not been conrmed yet because locating the conical section of the intersystem crossing is particularly challenging.
Figure 7 shows the reaction coordinates of the quartet
Figure 2. Catalytic cycle I: metalate mechanism.
Figure 3. Catalytic cycle II: (0) (+II) mechanism.
Figure 4. Chemical model of NiF 2/NHC catalyzed biaryl coupling.
Vol.69 No.11 2011 95 1289
69-1111_Hatakeyama.indd 95 2011/10/20 14:25:22
state (S3/2) and the doublet state (S1/2) for the cobalt catalyst, for which the energy proles are considerably more com- plicated than those of iron. The potential energy surfaces of the quartet state and the doublet state cross over each other during the oxidative addition process (solid and dashed lines, respectively). The cobaltate complex in the quartet state, SM1 Co q, is found to be more stable than the one in the doublet state, SM1 Co d (ΔΔE q d-8.7 kcal/mol). Alternatively, in transition structure of the oxidative addition, the quartet state TS1 Co q, is much higher in energy (+16.6 kcal/mol) than the
doublet state TS1 Co d. Likewise, the quartet state CP2 Co q is much less stable than the doublet state CP2 Co d (ΔΔE q d +19.9 kcal/mol) at the tetravalent cobaltate intermediate. These results indicate that the crossover of reaction pathways between the quartet and doublet states may take place during the oxidative addition process, where the C Cl bond cleavage takes place via TS1 Co d to give CP2 Co d in the doublet state.
Finally, the origin of the “uoride effect” was investigated using the same DFT calculations on the reactions of nickel
Figure 6. Energy proles of the oxidative addition to Fe II center based on the B3LYP/6 31G calculations. Relative electron energies based on SM1Fe q plus PhCl (E, kcal/ mol) are shown in parentheses (triplet state, S1: the dashed line, quintet state, S2: the solid line).
Figure 5. Reaction pathway for nickel uoride catalyzed cross coupling based on the DFT calculation (B3LYP/6 31G ) and its energy prole. Relative electron energies based on SM1 plus Ph Cl (E, kcal/mol) are shown in parentheses. Bond lengths are given in angstroms. Hydrogen atoms are omitted for clarity.
Figure 7. Energy proles of the oxidative addition to Co II center based on the B3LYP/6 31G calculations. Relative electron energies based on SM1Co q plus PhCl (E, kcal/ mol) are shown in parentheses (doublet state, S1/2: the dashed line, quartetstate, S3/2: the solid line).
69-1111_Hatakeyama.indd 96 2011/10/20 14:25:30
uoride and chloride with arylmagnesium reagents, where chemical models consisting of a PhMgBr, IMe, and either nickel salts of NiF 2 or NiCl 2 were adopted. This system corresponds to the control experiments described in Scheme 5 and Table 8. The (IMe)NiX 2 (XCl or F) systems were chosen as models for the starting nickel complex, and their reactions with phenylmagnesium chloride solvated with two molecules of dimethyl ether (PhMgCl·2Me 2O) were examined (Scheme 6 and Figure 8).
In each case of (IMe)NiCl 2 and (IMe)NiF 2 (denoted as SM0 XCl and SM0 XF, respectively), a single reaction pathway was obtained for the transmetalation process with PhMgCl·2Me 2O to form (IMe)NiPh 2 (denoted as SM4) via the formation of transmetalation intermediates SM1 XSM2 X, and SM3 X, as shown in Figure 8. The subsequent reductive elimination of biphenyl from the common intermediate SM4 gives the (IMe)Ni(0) biphenyl η 4 complex (denoted as PD2 ). The starting NHC nickel chloride complex SM0 XCl and PhMgCl·2Me 2O form, upon the release of one molecule of
Me 2O, a nickelate complex (SM1 XC1) with high exothermicity (ΔΔE-42.7 kcal/mol). Dissociation of MgCl 2·2Me 2O from the nickelate complex forms the neutral phenylnickel species (IMe)PhNiCl, SM2 XC1, which is 10.0 kcal/mol higher in energy than SM1 XC1. The reaction with the second molecule of PhMgCl·2Me 2O forms another nickelate intermediate carrying two phenyl groups (denoted as SM3 XC1) also in an exothermic manner (ΔΔE-28.7 kcal/mol). Diphenylnickel SM4 is formed by the endothermic dissociation of MgCl 2·2Me 2O (ΔΔE+10.9 kcal/mol). SM4 undergoes a reductive elimination to form a biphenyl complex of the nickel(0) species, PD2, via a three centered transition structure TS3 with a reasonable activation barrier and exothermic value (ΔE ‡+15.0 kcal/mol and ΔΔE-10.7 kcal/mol, respectively). The entire process starting from SM0 XCl to PD2 is exothermic (ΔΔE -61.2 kcal/mol) and the transformation from the initial nickelate complex SM1 XCl to PD2 is exothermic (ΔΔE-18.5 kcal/ mol). Considering the whole reaction pathway, the DFT study suggests that the reduction of NiCl 2 with a phenyl Grignard reagent is a facile process and strongly supports the experimental results summarized in Scheme 5 and Table 8.
The DFT calculations for the nickel uoride system provided a similar sequence of transformations from the starting SM0 XF to PD2, but the energy prole was different from that of the nickel chloride system. Transformation from SM1 XF to SM4 consists of four steps: 1) formation of monophenylnicke- late complex SM1 XF (ΔΔE-71.2 kcal/mol) 2) formation of divalent phenylnickel halide SM2 XF upon the dissociation of MgClF·2Me 2O (ΔΔE+37.0 kcal/mol), 3) formation of diphenylnickelate complex SM3 XF (ΔΔE-42.9 kcal/mol), and 4) formation of diphenylnickel species SM4 upon the dis-
Scheme 6. Chemical models of homocoupling of aryl Grignard reagent by nickel halides as shown in entris 4 and 8 in Table 8.
Figure 8. Energy proles of the reaction shown in Scheme 6. Comparison of the electron energies of the stationary points (B3LYP/6 31G ) was done by compensating the electron energies of the metal species and Me 2O molecules shown in the brackets, which are detached or attached to the intermediates upon the corresponding transformation, and the energy differences thus obtained are shown as the relative energies based on SM4 (ΔE, kcal/mol) in parentheses. The dashed line represents the reaction pathway of nickel chloride (XCl), and the hashed bold line that of nickel uoride (XF).
Vol.69 No.11 2011 97 1291
69-1111_Hatakeyama.indd 97 2011/10/20 14:25:35
sociation of MgClF·2Me 2O (ΔΔE+17.6 kcal/mol). After the formation of SM4, each reaction pathway of nickel chloride and uoride merged into an identical reductive elimination pathway. Although the overall process from SM0 XF to PD2 is exothermic (ΔΔE-70.2 kcal/mol), energy minima of the nickel uoride system are at the stages of the organonickelate intermediates, SM1 XF and SM3 XF (ΔΔE-1.0 and -6.9 kcal/mol, respectively). The most signicant difference between the chloride and uoride pathways is the highly endothermic nature of the formation of the phenylnickel halide intermediates SM2 X from the nickelates SM1 X (ΔΔE +37.0 kcal/mol and +10.0 kcal/mol from SM1 XF and SM1 XC1, respectively). Cleavage of a stable Ni F bond is energetically unfavorable and is presumably the origin of the large endothermic value. The large electronegativity of uorine may account for the stabilization of the uorinated nickelate complex and contribute in part to the enhancement of the uphill energy difference. It should be noted that the activation barrier of the PhCl oxidative addition to SM1 XF is much lower (ΔE ‡+28.0 kcal/mol as in Figure 5) than the energy of SM2 XF (ΔΔE+37.0 kcal/mol). The present DFT calculations show that SM1 XF is a reactive intermediate, preferring the oxidative addition of an aryl halide substrate rather than the transmetalation step, and hence, a prime catalytically active candidate in the nickel uoride/NHC catalyzed biaryl cross coupling. The similar theoretical evaluation for iron and cobalt uoride/NHC systems revealed the preference for oxidative addition of the metalate species, such as SM1 Fe and SM1 Co over the formation of the corresponding transmetalation products.
Based on the results of the control experiments and theoretical studies, it was concluded that strong coordination of the uoride ion to the metal center of iron, cobalt, and nickel sup- presses the initial transmetalation and reduction processes, which promote undesired homocoupling reactions. The uoride ligands remain coordinated to the metal center throughout the catalytic cycle even with a large excess of Grignard reagents under catalytic reaction conditions. Furthermore, the resulting heteroleptic metalate(II) complex, such as SM1, undergoes oxidative addition of aryl chlorides with a reasonable activation energy. A low activation barrier for the reductive elimination from the resulting high valent intermediate can account for the characteristically high cross/homo selectivity of the present IGM uoride/NHC catalyzed biaryl cross coupling reactions.
3 Nickel Catalyzed Alkenylative Cross Coupling between Alkyl Aryl Suldes and Aryl Grignard Reagents
3.1 Background Despite a long history starting with independent publica-
tions by Wenkert 58 and Takei 59 in 1979, organosulfur compounds 60 have received far less attention as electrophilic substrates in cross coupling chemistry than other substrates, such as halides, sulfonates, and phosphates. The underuse of organosulfur compounds is partly due to their malodorous smell 61 and the perception that they are a lesser substitute for other electrophiles. Although it has been shown that their reactivity is virtually the same as those of the widely used organic halides and pseudohalides, 62 we found a new reactivity of alkyl aryl sulde toward aryl Grignard reagents during our study on nickel/NHC catalyzed cross coupling described in
the preceding section. The ample supply of sulfur sources, 63 especially as renery byproducts in industrial chemistry, has provided the motivation for a detailed study using organosulfur compounds to develop novel Ni catalyzed “alkenylative” cross coupling reactions. The proposed arylation occurs at the alkyl substituent of the sulde substrate (not at the aryl substituent) with the simultaneous addition of an olenic substituent at the reaction center (Scheme 7). 64
3.2 Alkenylative Cross Coupling: Catalyst Screening and Scope of the Reaction
Table 9 summarizes the results of the catalyst screening. In the presence of Ni(cod) 2, the highest yield (92%) of the desired alkenylative coupling product 6 was obtained after 6 h at 60 by using saturated type NHC ligand precursor, SIPr·HCl (entry 1). The reactions using the original NHC ligand, SIPr, or the NHC ligand precursors, IPr·HCl and SIMes·HCl, displayed varied selectivity and decreased yields (entries 2, 3, and 4) as compared to SIPr·HCl. Ni(acac) 2 and NiCl 2 showed lower catalytic activity and required a higher reaction temperature, 80 , for complete conversion (entries 5 and 6). While phosphine ligands improved the yield of the biaryl coupling product 7, the desired alkenylative coupling product 6 was not isolated (entries 7 10). In the absence of a nickel catalyst, the coupling reactions were not effective (entry 11).
The scope of the present nickel catalyzed alkenylative cross coupling reaction is shown in Table 10. The reactions of dodecyl suldes possessing an electron rich, electron poor, or bulky aryl group all afforded the alkenylative coupling products in high yields with excellent E/Z selectivity. The parent dodecyl phenyl sulde reactions performed optimally with the highest yields (entries 1 5).
Secondary alkyl aryl suldes display alkenlylative coupling reactivity, which was investigated using cyclohexyl (or cyclo- heptyl) phenyl sulde reacted with a variety of aryl Grignard
Scheme 7. Alkenylative cross coupling of alkyl aryl sulde.
Table 9. Catalyst screening on the alkenylative cross coupling of dodecyl phenyl sulde with p TolMgBr.
69-1111_Hatakeyama.indd 98 2011/10/20 14:25:38
reagents bearing dimethylamino, methoxy, methyl, and uoro substituents to afford the corresponding arylated cycloalkenes in good to excellent yields (entries 6 9, 13). The reaction was rather sensitive to steric demands of the aryl nucleophile, and thus, the coupling product yields using o tolyl and mesityl Grignard reagents were poor (entries 10 and 11). However, the 2 naphthyl Grignard reagent participated in the reaction (entry 12).
Excellent E/Z selectivity was achieved in the formation of a di substituted acyclic olen, exemplied by the stereoselective synthesis of the E stilbene derivative (entry 14). Conversely, a low selectivity was observed in the formation of a tri substituted olen (entry 15). The results may be accounted for by the non stereoselective formation of enethiolate intermediates (see the mechanistic discussion below). When a non symmetrical secondary alkyl sulde was subjected to the reaction condi-
tions, the corresponding internal olen 8 and terminal olen 9 were obtained in a ratio of 46:54. Note that the stereoselectiv- ity of 8 is exceptionally high (entry 16). The olen moiety in the sulde substrate did not interfere with the coupling reaction (entry 17). In entry 18, the reaction of 8 phenylthio 1,4 dioxaspiro[4,5]decane gave a double arylation product, 8,8 diphenyl 1,4 dioxaspiro [4,5]decane (37% yield), and the expected alkenylative coupling product (43% yield). The geminal diarylation products were also found as minor by products (1 3% yields) in all entries. The formation mechanism is dis- cussed in the next section. 3.3 Mechanistic Considerations: How does the alkenylation
occur? In Figure 9, we propose a mechanism based on the experi-
mental observations, 65,66 computational studies (Figures 10 and 11), and related literature reports. 67 72 The catalytic cycle starts with the oxidative addition of an alkyl phenyl sulde to Ni(0) species A to afford phenylnickel(II) intermediate B. Successive β hydride elimination and reductive elimination of the benzene affords Ni(0) thioaldehyde complex C. The use of a bulky NHC ligand should suppress the conventional biaryl coupling pathway (A B D). The thioaldehyde then undergoes deprotonation via the reaction with ArMgBr to produce Ni(0) enethiolate complex E. 67,68 Following C S bond cleavage affords alkenyl nickel(II) F. 69 Transmetalation between F and ArMgBr yields diorganonickel product G as well as the MgBr 2 and MgS byproducts. 70 Reductive elimination gives the alkenylative coupling product, such as 6, with the regeneration of the active species A. The diarylation may proceed via addition of an aryl Grignard reagent to thiocarbonyl intermediate C 71 followed by nickel catalyzed arylation of the resulting benzyl- thiolate. 72
DFT calculations provide deeper insights into the alkenylative coupling reaction (Figures 10 and 11 show DFT calculations for specic parts of Figure 9). Figure 10 shows the reaction pathways for oxidative addition. Ni(0) complex A with π coordination and Ni(0) complex A’ with sulde coordination are in equilibrium with each other (where Lthe ethyl phenyl sulde substrate from Figure 9). Aromatic carbon sulde bond cleavage of A takes place via TS A B requiring activation energy (ΔG ‡2.0 kcal/mol). The total activation barrier from A’ to TS A B was calculated as 6.8 kcal/mol, which was lower than the aliphatic carbon sulde bond cleavage via TS A’ INT (11.5 kcal/mol). The calculations suggest that the predominant formation species is phenylnickel(II) B. Regarding the transformation from B to C, an unprecedented transition structure
Figure 9. A plausible mechanism.
Table 10. Substrate scope of alkenylative cross coupling.
Vol.69 No.11 2011 99 1293
69-1111_Hatakeyama.indd 99 2011/10/20 14:25:46
Figure 11. Reaction pathway for the reductive β hydride elimination process (B to C) and the transmetalation process (B to D) and its energy proles. Relative Gibbs free energies to B (ΔG, kcal/mol, B3LYP/6 311+G(d,p) SDD//B3LYP/6 31G- (d) LANL2DZ) are shown in parentheses. Bond lengths are given in angstroms.
Figure 10. Reaction pathway for oxidative addition process (A to B, A to INT) and its energy prole. Relative Gibbs free energies to A (ΔG, kcal/mol, B3LYP/6 311+G(d,p) SDD//B3LYP/6 31G(d) LANL2DZ) are shown in parentheses. Bond lengths are given in angstroms.
69-1111_Hatakeyama.indd 100 2011/10/20 14:25:53
model was obtained (Figure 11). Here, B (where RH, Lnone from Figure 9) isomerizes to B’, in which an agostic Ni H interaction is present. A concerted β hydride reductive elimination of benzene takes place via ve centered transition structure TS B C to form Ni(0) thioaldehyde complex C. Alter- natively, the transmetalation from B to D takes place via transition structure TS B D resembling that in σ bond metathesis. The relative Gibbs free energy of TS B D was calculated as 3.0 kcal/mol, which is higher than that of TS B C, probably a result of the steric demand by the bulky SIPr ligand at TS B D. The computational results are in accordance with the experimental results, indicating the selective alkenylative coupling product formation in the presence of SIPr.
4 Conclusions
Two novel C sp 2 C sp 2 cross coupling reactions catalyzed by iron group metals (IGMs) with N heterocyclic carbene (NHC) ligands were developed. Combinations of NHCs and IGM uoride salts were demonstrated to be excellent catalysts for highly selective biaryl cross coupling reactions between aryl Grignard reagents and aryl or heteroaryl halides. The formation of homocoupling byproducts, which often becomes a critical issue in industrial settings, was suppressed markedly by appropriate choices of the metal uoride/NHC combination. Based on stoichiometric control experiments and theoretical studies, the origin of the unique “uoride effect” was explained by the formation of a higher valent heteroleptic metalate species, [Ar 1M IIF 2]MgBr (MFe, Co, Ni) as the key intermediate. During our continuing exploration for new reactivity of IGM/ NHC catalysts, an unprecedented alkenylative cross coupling reaction was developed by using a Ni(0)/SIPr catalyst. The alkyl aryl suldes cross coupled with aryl Grignard reagents, producing various styrene derivatives via formal alkyl aryl coupling followed by dehydrogenation. The IGM/NHC catalyzed cross coupling reactions described in the present report provide a selective and practical synthetic method for unsymmetrical biaryls and alkenylated aromatic compounds. Addi- tionally, the results offer new mechanistic insights into IGM catalyzed cross coupling reactions. The present study displays new synthetic potentials of IGM/NHC catalysts by using what were considered non orthodox combinations of metal catalysts, ligands and substrates, and illustrates that the exploration of new selectivity and reactivity of the catalyst system can lead us to deeper mechanistic understandings. Although numerous studies have been conducted on the IGM/NHC catalyst, end- less selectivity and reactivity properties remain to be discovered and will be the focus of future work.
Acknowledgment The authors are grateful to Dr. Hirofumi Seike, Mr. Sigma
Hashimoto, and all the co workers, whose names appear in the references, for their invaluable intellectual and experimental contributions to the cross coupling chemistry described in this article. The present work is based on our research projects, which are supported by Grant in Aids for Scientic Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan. Financial support from Tosho Fine Chemi- cal and Tosho Corporation are gratefully acknowledged.
References and Footnotes 1 (a) Wanzlick, H. W.; Schönherr, H. J. Angew. Chem. Int. Ed. 1968, 7,
141. (b) Öfele, K. J. Organomet. Chem. 1968, 12, P42. 2 Arduengo, A. J., III; Harlow, R. L.; Kline, M. J. Am. Chem. Soc.
1991, 113, 361. 3 Benhamou, L.; Chardon, E.; Lavigne, G.; Bellemin Laponnaz, S.;
César, V. Chem. Rev. 2011, 111, 2705. 4 Díez González, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109,
3621. 5 (a) Samojilowicz, C.; Bieniek, M.; Grela, K. Chem. Rev. 2009, 109,
3708. (b) Alcaide B, Almendros, P.; Luna, A. Chem. Rev. 2009, 109, 3817. (c) Vougioukalakis, G. C.; Grubbs, R. H. Chem. Rev. 2010, 110, 1746.
6 Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem. Int. Ed. 2007, 46, 2768.
7 (a) Diéz González, S.; Nolan, S. P. Coord. Chem. Rev. 2007, 251, 874. (b) Radius, U.; Bickelhaupt, F. M. Coord. Chem. Rev. 2009, 253, 678. (c) Jacobsen, H.; Correa, A.; Poater, A.; Costabile, C.; Cavallo, L. Coord. Chem. Rev. 2009, 253, 687.
8 (a) Böhm, V. P. W.; Weskamp, T.; Gstöttmayr, C. W. K.; Herrmann, W. A. Angew. Chem., Int. Ed. 2000, 39, 1602. (b) Böhm, V. P. W.; Gstöttmayr, C. W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem. Int. Ed. 2001, 40, 3387.
9 Iron/NHC catalyzed cross coupling reactions: (a) Bedford, R. B.; Betham, M.; Bruce, D. W.; Danopoulos, A. A.; Frost R. M.; Hird, M. J. Org. Chem. 2006, 71, 1104. (b) Plietker, B.; Dieskau, A.; Moews, K.; Jatsch, A. Angew. Chem. Int. Ed. 2008, 47, 198. Cobalt/NHC: (c) Someya, H.; Ohmiya, H.; Yorimitsu, H.; Oshima, K. Org. Lett. 2007, 9, 1565. Nickel/NHC: (d) Blakey, S.; MacMilan, W. C. J. Am. Chem. Soc. 2003, 125, 6046. (e) Omar Amrani, R.; Thomas, A.; Brenner, E.; Schneider, R.; Fort, Y. Org. Lett. 2003, 5, 2311. (f) Liu, J.; Robins, M. J. Org. Lett. 2004, 6, 3421. (g) Schaub, T.; Backes, M.; Radius, U. J. Am. Chem. Soc. 2006, 128, 15964. (h) Matsubara, K.; Ueno, K.; Koga, Y.; Hara, K. J. Org. Chem. 2007, 72, 5069. (i) Zhang, Y.; Ngeow, K. C.; Ying, J. Y. Org. Lett. 2007, 9, 3495. (j) Gao, C. Y.; Yang, L. M. J. Org. Chem. 2008, 73, 1624. (k) Shimasaki, T.; Tobisu, M.; Chatani, N. Angew. Chem. Int. Ed. 2010, 49, 2929. Other reactions, see reference 4 and citations therein.
10 Clavier, H.; Nolan, S. P. Chem. Commun. 2010, 841. 11 (a) Demus, D.; Goodby, J. W.; Gray, G. W.; Spiess, H. W.; Vill, V.
Eds.; Handbook of Liquid Crystals; Wiley VCH: Weinheim, 1998. (b) Mitschke, U.; Bauerle, P. J. Mater. Chem. 2000, 10, 1471. (c) Yamamoto, T. J. Organomet. Chem. 2002, 653, 195. (d) Baudoin, O.; Gueritte, F. Stud. Nat. Prod. Chem., Part J 2003, 29, 355. (e) Holder, E.; Langeveld, B. M. W.; Schubert, U. S. Adv. Mater. 2005, 17, 1109. (f) Ambade, A. V.; Savariar, E. N.; Thayumanavan, S. Molecular Phar- maceutics 2005, 2, 264. (g) Doucet, H.; Hierso, J. C. Curr. Opin. Drug Discover. Devel. 2007, 10, 672. (h) Abe, H.; Harayama, T. Heterocycles 2008, 75, 1305.
12 (a) Cepanec, I., Ed.; Synthesis of Biaryls; Elsevier Ltd: Oxford, 2004. (b) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359. (c) Nelson, T. D.; Crouch, R. D. Organic Reactions 2004, 63, 265. (d) Corbet, J. P.; Mignani, G. Chem. Rev. 2006, 106, 2651.
13 (a) de Meijere, A.; Diederich, F., Eds.; Metal Catalyzed Cross coupling Reactions, 2nd ed.; Wiley VCH: New York, 2004. (b) Miyaura, N., Ed.; Cross Coupling Reactions: A Practical Guide; Springer: Ber- lin, 2002.
14 Amatore, M.; Gosmini, C. Angew. Chem. Int. Ed. 2008, 47, 2089 and citations therein.
15 Kharasch, M. S.; Fields, E. K. J. Am. Chem. Soc. 1941, 63, 2316. 16 Recent papers: (a) Nagano, T.; Hayashi, T. Org. Lett. 2005, 7, 491. (b)
Cahiez, G.; Chaboche, C.; Mahuteau Betzer, F.; Ahr, M. Org. Lett. 2005, 7, 1943. (c) Cahiez, G.; Moyeux, A.; Buendia, J.; Duplais, C. J. Am. Chem. Soc. 2007, 129, 13788. Without metal catalysts: (d) Krasovskiy, A.; Tishkov, A.; del Amo, V.; Mayr, H.; Knochel, P. Angew. Chem. Int. Ed. 2006, 45, 5010.
17 (a) de Meijere, A.; Diederich, F., Eds.; Metal Catalyzed Cross coupling Reactions, 2nd ed.; Wiley VCH: Germany, 2004. (b) Miyaura, N., Ed.; Cross Coupling Reactions: A Practical Guide; Springer: Ber- lin, 2002. (c) Stanforth, S. P. Tetrahedron 1998, 54, 263.
18 (a) Snieckus, V. Chem. Rev. 1990, 90, 879. (b) Murahashi, S. J. Organomet. Chem. 2002, 653, 27. (c) Anctil, E. J. G.; Snieckus, V. J. Organomet. Chem. 2002, 653, 150. (d) Nájera, C.; Sansano, J. M.; Yus, M. Tetrahedron 2003, 59, 9255.
19 (a) Tamao, K. J. Organomet. Chem. 2002, 653, 23. (b) Banno, T.; Hayakawa, Y.; Umeno, M. J. Organomet. Chem. 2002, 653, 288. (c) Knochel, P.; Dohle, W.; Gommermann, N.; Kneisel, F. F.; Kopp, F.; Korn, T.; Sapountzis, I.; Vu, V. A. Angew. Chem. Int. Ed. 2003, 42,
Vol.69 No.11 2011 101 1295
69-1111_Hatakeyama.indd 101 2011/10/20 14:25:54
4302. (d) Ila, H.; Baron, O.; Wagner, A. J.; Knochel, P. Chem. Lett. 2006, 35, 2. (e) Terao, J.; Kambe, N. Acc. Chem. Res. 2008, 41, 1545.
20 (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (b) Lloyd Williams, P.; Giralt, E. Chem. Soc. Rev. 2001, 30, 145. (c) Miyaura, N. J. Organomet. Chem. 2002, 653, 54. (d) Suzuki, A. J. Organomet. Chem. 2002, 653, 83. (e) Miyaura, N. Top. Curr. Chem. 2002, 219, 11. (f) Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002, 58, 9633. (g) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419. (h) Ishiyama, T.; Miyaura, N. Pure Appl. Chem. 2006, 78, 1369. (i) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275. (j) Darses, S.; Genet, J. P. Chem. Rev. 2008, 108, 288. (k) Doucet, H. Eur. J. Org. Chem. 2008, 2013.
21 (a) Hiyama, T.; Hatanaka, Y. Pure Appl. Chem. 1994, 66, 1471. (b) Hiyama, T.; Shirakawa, E. Top. Curr. Chem. 2002, 219, 61 (c) Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002, 35, 835. (d) Hiyama, T. J. Organomet. Chem. 2002, 653, 58. (e) Denmark. S. E.; Pan, W. J. Organomet. Chem. 2002, 653, 98. (f) Denmark. S. E.; Ober, M. H. Aldrichimica Acta 2003, 36, 75. (g) Spivey, A. C.; Gripton, C. J. G.; Hannah, J. P. Curr. Org. Synth. 2004, 1, 211. (h) Denmark, S. E.; Baird, J. D. Chem. Eur. J. 2006, 12, 4954. (i) Denmark, S. E.; Regens, C. S. Acc. Chem. Res. 2008, 41, 1486.
22 (a) Taylor, R. J. K. Ed.; Organocopper Reagents; Oxford University Press: Oxford, 1994. (b) Lipshutz, B. H. Acc. Chem. Res., 1997, 30, 277. (c) Krause, N.; Gerold, A. Angew. Chem., Int. Ed. Engl. 1997, 36, 187. (d) Woodward, S. Chem. Soc. Rev. 2000, 29, 393. (e) Krause, N. Ed.; Modern Organocopper Chemistry; Wiley VCH: Weinheim, 2002. (f) Nakamura, E.; Mori, S. Angew. Chem. Int. Ed. 2000, 39, 3751. (g) Caprio, V. Lett. Org. Chem. 2006, 3, 339.
23 (a) Negishi, E. Acc. Chem. Res. 1982, 15, 340. (b) Knochel, P.; Jones, P. Eds.; Organozinc Reagents; Oxford University Press: Oxford, 1999. (c) Negishi, E. J. Organomet. Chem. 2002, 653, 34. (d) Lessene, G. Aust. J. Chem. 2004, 57, 107. (e) Zvi, R.; Marek, I. Eds.; Chemistry of Organozinc Compounds; John Wiley: Chichester, 2006.
24 (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b) Mitchell, T. N. J. Organomet. Chem. 1986, 304, 1. (c) Mitchell, T. N. Synthesis 1992, 803. (d) Kosugi, M.; Fugami, K. J. Organomet. Chem. 2002, 653, 50. (e) Espinet, P.; Echavarren. A. M. Angew. Chem. Int. Ed. 2004, 43, 4704. (f) Echavarren. A. M. Angew. Chem. Int. Ed. 2005, 44, 3962.
25 Reviews: (a) Iron Catalysis in Organic Chemistry; Plietker, B., Ed.; Wiley VCH: Weinheim, 2008. (b) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev. 2004, 104, 6217. (c) Shinokubo, H.; Oshima, K. Eur. J. Org. Chem. 2004, 2081. (d) Fürstner, A.; Martin, R. Chem. Lett. 2005, 34, 624. (e) Correa, A.; Mancheño, O. G.; Bolm, C. Chem. Soc. Rev. 2008, 37, 1108. (f) Sherry, B. D.; Fürstner, A. Acc. Chem. Res. 2008, 41, 1500. (g) Czaplik, W. M.; Mayer, M.; Cvengros, J.; Wangelin, A. J. V. Chem. Sus. Chem. 2009, 2, 396. (h) Nakamura, E.; Yoshikai, N. J. Org. Chem. 2010, 75, 6061.
26 Iron catalyzed cross coupling reactions of sp 2 carbon electrophiles: (a) Tamura, M.; Kochi, J. K. J. Am. Chem. Soc. 1971, 93, 1487. (b) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199. (c) Fürstner, A.; Leitner, A.; Méndez, M.; Krause, H. J. Am. Chem. Soc. 2002, 124, 13856. (d) Necas, D.; Kotora, M.; Císarová, I. Eur. J. Org. Chem. 2004, 1280. (e) Duplais, C.; Bures, F.; Sapountzis, I.; Korn, T. J.; Cahiez, G.; Knochel, P. Angew. Chem. Int. Ed. 2004, 43, 2968. (f) Itami, K.; Higashi, S.; Mineno, M.; Yoshida, J. Org. Lett. 2005, 7, 1219. (j) Dunet, G.; Knochel, P. Synlett 2006, 407. (g) Cahiez, G.; Gager, O.; Habiak, V. Synthesis 2008, 2636. (l) Cahiez, G.; Habiak, V.; Gager, O. Org. Lett. 2008, 10, 2389. (h) Carril, M.; Correa, A.; Bolm, C. Angew. Chem. Int. Ed. 2008, 47, 4862. (i) Hatakeyama, T.; Yoshimoto, Y.; Gabriel, T.; Nakamura, M. Org. Lett. 2008, 10, 5341. (j) Fürstner, A.; Martin, R.; Krause, H.; Seidel, G.; Goddard, R.; Lehmann, C. W. J. Am. Chem. Soc. 2008, 130, 8773. (k) Li, B. J.; Xu, L.; Wu, Z. H.; Guan, B. T.; Sun, C. L.; Wang, B. Q.; Shi, Z. J. J. Am. Chem. Soc. 2009, 131, 14656.
27 Iron catalyzed cross coupling reactions of sp 3 carbon electrophiles: (a) Nakamura, M.; Matsuo, K.; Ito, S.; Nakamura, E. J. Am. Chem. Soc. 2004, 126, 3686. (b) Nagano, T.; Hayashi, T. Org. Lett. 2004, 6, 1297. (c) Martin, R.; Fürstner, A. Angew. Chem. Int. Ed. 2004, 43, 3955. (d) Bedford, R. B.; Bruce, D. W.; Frost, R. M.; Goodby, J. W.; Hird, M. Chem. Commun. 2004, 2822. (e) Nakamura, M.; Ito, S.; Matsuo, K.; Nakamura, E. Synlett 2005, 1794. (f) Bedford, R. B.; Betham, M.; Bruce, D. W.; Danopoulos, A. A.; Frost, R. M.; Hird, M. J. Org. Chem. 2006, 71, 1104. (g) Plietker, B. Angew. Chem. Int. Ed. 2006, 45, 1469. (h) Dongol, K. G.; Koh, H.; Sau, M.; Chai, C. L. L. Adv. Synth. Cat. 2007, 349, 1015. (i) Cahiez, G.; Habiak, V.; Duplais, C.; Moyeux, A. Angew. Chem. Int. Ed. 2007, 46, 4364. (j) Cahiez, G.;
Duplais, C.; Moyeux, A. Org. Lett. 2007, 9, 3253. (k) Guérinot, A.; Reymond, S.; Cossy, J. Angew. Chem. Int. Ed. 2007, 46, 6521. (l) Rao Volla, C. M.; Vogel P. Angew. Chem. Int. Ed2008, 47, 1305. (m) Bedford, R. B.; Huwe, M.; Wilkinson, M. C. Chem. Commun, 2009, 600. (n) Hatakeyama, T.; Kondo, Y.; Fujiwara, Y.; Takaya, H.; Ito, S.; Nakamura, E.; Nakamura, M. Chem. Commun. 2009, 1216. (o) Hatakeyama, T.; Hashimoto, T.; Kondo, Y.; Fujiwara, Y.; Seike, H.; Takaya, H.; Tamada, Y.; Ono, T.; Nakamura, M. J. Am. Chem. Soc. 2010, 132, 10674. (p) Kawamura, S.; Ishizuka, K.; Takaya. H.; Nakamura, M. Chem. Commun. 2010, 46, 6054. (q) Hatakeyama, T.; Okada, Y.; Yoshimoto, Y.; Namamura, M. Angew. Chem. Int. Ed. DOI: 10.1002/anie.201104125. (r) Hatakeyama, T.; Fujiwara, Y.; Okada, Y.; Itoh, T.; Hashimoto, T.; Kawamura, S.; Ogata, K.; Takaya, H.; Nakamura, M. Chem. Lett. 2011, 40, 1030.
28 Hatakeyama, T.; Nakamura, M. J. Am. Chem. Soc. 2007, 129, 9844. 29 (a) Asymmetric Mukaiyama Aldol reaction (copper): Krüger, J.;
Carreira, E. M. J. Am. Chem. Soc. 1998, 120, 837. (b) Allylation reaction (titanium): Gauthier, D. R.; Carreira, E. M. Angew. Chem., Int. Ed. Engl. 1996, 35, 2363. (c) Hydroamination reaction (iridium): Dorta, R.; Egli, P.; Zürcher, F.; Togni, A. J. Am. Chem. Soc. 1997, 119, 10857. (d) Hydrosilylation reaction (titanium): Verdaguer, X.; Lange, U. E. W.; Reding, M. T.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 6784.
30 Reviews: (a) Pagenkopf. B. L.; Carreira, E. M. Chem. Eur. J. 1999, 5, 3437. (b) Fagnou, K.; Lautens, M. Angew. Chem. Int. Ed. 2002, 41, 26.
31 Concomitant halide effect on palladium or nickel catalyzed cross coupling and Heck reactions has been investigated for chloride, bromide, and iodide ions, but not for uoride ions: Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314 and citations therein.
32 Activation of organometallic compounds using a stoichiometric amount of uoride ions in cross coupling reactions. Boron: (a) Wright, S. W.; Hageman, D. L.; McClure, L. D. J. Org. Chem. 1994, 59, 6095. (b) Darses, S.; Michaud, G.; Genet, J. P. Eur. J. Org. Chem. 1999, 1875. (c) Molander, G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302. Silane: (d) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918. (e) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121, 5821. (f) Lee, H. M.; Nolan, S. P. Org. Lett. 2000, 2, 2053. (g) Itami, K.; Nokami, T.; Ishimura, Y.; Mitsudo, K.; Kamei, T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123, 11577. Tin: (h) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 1999, 38, 2411. (i) Grasa, G. A.; Nolan, S. P. Org. Lett. 2001, 3, 119. (j) Mee, S. P. H.; Lee, V.; Baldwin, J. E. Angew. Chem. Int. Ed. 2004, 43, 1132.
33 (a) Korn, T. J.; Cahiez, G.; Knochel, P. Synlett 2003, 1892. (b) Ohmiya, H.; Yorimitsu, H.; Oshima, K. Chem. Lett. 2004, 33, 1240. (c) Korn, T. J.; Knochel, P. Angew. Chem. Int. Ed. 2005, 44, 2947. (d) Korn, T. J.; Schade, M. A.; Wirth, S.; Knochel, P. Org. Lett. 2006, 8, 725. (e) Korn, T. J.; Schade, M. A.; Cheemala, M. N.; Wirth, S.; Guevara, S. A.; Cahiez, G.; Knochel, P. Synthesis 2006, 3547.
34 (a) Corriu, R. J. P.; Masse, J. P. J. Chem. Soc., Chem. Commun. 1972, 144. (b) Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972, 94, 4374. (c) Tamao, K.; Sumitani, K.; Kiso, Y.; Zembayashi, M.; Fujioka, A.; Kodama, S.; Nakajima, I.; Minato, A.; Kumada, M. Bull. Chem. Soc. Jpn. 1976, 49, 1958. (d) Dankwardt, J. W. Angew. Chem. Int. Ed. 2004, 43, 2428. (e) Ackermann, L.; Born, R.; Spatz, J. H.; Meyer, D. Angew. Chem. Int. Ed. 2005, 44, 7216. (f) Yoshikai, N.; Mashima, H. Nakamura, E. J. Am. Chem. Soc. 2005, 127, 17978. (g) Matsubara, K.; Ueno, K.; Shibata, Y. Organometallics 2006, 25, 3422.
35 Hatakeyama, T.; Hashimoto, S.; Ishizuka, K.; Nakamura, M. J. Am. Chem. Soc. 2009, 131, 11949.
36 (a) Quintin, J.; Franck, X.; Hocquemiller, R.; Figadére, B. Tetrahedron Lett. 2002, 43, 3547. (b) Sapountzis, I.; Lin, W. W.; Konk, C. C.; Despotopoulou, C.; Knochel, P. Angew. Chem. Int. Ed. 2005, 44, 1654. (c) Konk, C. C.; Blank, B.; Pagano, S.; Götz, N.; Knochel, P. Chem. Commun. 2007, 1954.
37 (a) Norinder, J.; Matsumoto, A.; Yoshikai, N.; Nakamura, E. J. Am. Chem. Soc. 2008, 130, 5858. (b) Yoshikai, N.; Matsumoto, A.; Norinder, J.; Nakamura, E. Angew. Chem. Int. Ed. 2009, 48, 2925.
38 In FeF 3·3H 2O and FeF 2·4H 2O, each iron atom is surrounded by uorine atoms and water molecules in the form of a nearly regular octa- hedron. The conformation can account for the increased solubility of FeF 3·3H 2O and FeF 2·4H 2O compared to FeF 3 and FeF 2, in which the iron atom is surrounded by six uorine atoms. Please refer to: (a) Hepworth, M. A.; Jack, K. H.; Peacock, R. D.; Westland, G. J. Acta Cryst. 1957, 10, 63. (b) Penfold, B. R.; Taylor, M. R. Acta Cryst. 1960, 13, 953. (c) Teufer, G. Acta Cryst. 1964, 17, 1480. (d) Jørgensen, J. E.; Smith, R. I. Acta Cryst. 2006, B62, 987.
39 In situ NHC ligand generation: Herrmann, W. A. Angew. Chem. Int.
69-1111_Hatakeyama.indd 102 2011/10/20 14:25:55
Ed. 2002, 41, 1290 and citations therein. 40 Although alkyl Grignard reagents possessing β hydrogens are known
to reduce some iron (III) and also iron (II) salts to zero or lower oxidation states (see ref 26j and citations therein), it is proposed here that the coordinating uoride ion may hamper the full reduction of the iron salts. The experimental basis for this proposal was the stoichiometric control experiments and theoretical studies described in the later part of the manuscript.
41 Tiecco, M.; Testaferri, L.; Tingoli, M. Tetrahedron Lett. 1982, 23, 4629.
42 Recent reviews: (a) Shinokubo, H.; Oshima, K. Eur. J. Org. Chem. 2004, 2081. (b) Blekkan, E. A.; Borg, O.; Froeseth, V.; Holmen, A. Catalysis 2007, 20, 13. (c) Gosmini, C.; Bégouin, J. M.; Moncomble, A. Chem. Commun. 2008, 3221. (d) Hess, W.; Treutwein, J.; Hilt, G. Synthesis 2008, 3537. (e) Jeganmohan, M.; Cheng, C. H. Chem. Eur. J. 2008, 14, 10876.
43 Recent reviews: (a) Suginome, M.; Ito, Y. J. Organomet. Chem. 2003, 680, 43. (b) Montgomery, J. Angew. Chem. Int. Ed. 2004, 43, 3890. (c) Netherton, M. R.; Fu, G. C. Adv. Synth. Cat. 2004, 346, 1525. (d) Tamaru, Y. Ed.; Modern Organonickel Chemistry; Wiley VCH: Weinheim, 2005. (e) Montgomery, J.; Sormunen, G. J. Top. Curr. Chem. 2007, 279, 1. (f) Kimura, M.; Tamaru, Y. Top. Curr. Chem. 2007, 279, 173. (g) Mori, M. Eur. J. Org. Chem. 2007, 4981. (h) Ng, S. S.; Ho, C. Y.; Schleicher, K. D.; Jamison, T. F. Pure. Appl. Chem. 2008, 80, 929. (i) Nakao, Y.; Hiyama, T. Pure. Appl. Chem. 2008, 80, 1097. (j) Hirano, K.; Yorimitsu, H.; Oshima, K. Chem. Commun. 2008, 3234.
44 Reviews for transition metal uoride: (a) Doherty, N. M.; Hoffmann, N. W. Chem. Rev. 1991, 91, 553. (b) Murphy, E. F.; Murugavel, R.; Roesky, H. W. Chem. Rev. 1997, 97, 3425. (c) Mezzetti, A.; Becker, C. Helv. Chem. Acta 2002, 85, 2686
45 Kumada, M. Pure Appl. Chem. 1980, 52, 669. 46 Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D.; Wenkert, E. Tet-
rahedron Lett. 1982, 23, 4629. 47 Uchino, M.; Yamamoto, A.; Ikeda, S. J. Organomet. Chem. 1970, 24,
C63. 48 Fürstner et al. reported that a divalent tetraphenylferrate complex,
[Ph 4Fe]Li 2, is prone to decompose thermally to give biphenyl in the presence or absence of an oxidant. See ref. 26j.
49 Wakabayashi, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2001, 123, 5374.
50 (a) Terao, J.; Watanabe, H.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2002, 124, 4222. (b) Terao, J.; Todo, H.; Watanabe, H.; Ikumi, A.; Kambe, N. Angew. Chem. Int. Ed. 2004, 43, 6180.
51 Organometal (IV) compounds: (a) Bower, B. K.; Tennent, H. G. J. Am. Chem. Soc. 1972, 94, 2512. (b) Byrne, E. K.; Theopold, K. H. J. Am. Chem. Soc. 1989, 111, 3887. (c) Dimitrov, V.; Linden, A. Angew. Chem. Int. Ed. 2003, 42, 2631. (d) Carnes, M.; Buccella, D.; Chen, J. Y. C.; Ramirez, A. P.; Turro, N. J.; Nuckolls, C.; Steigerwald, M. Angew. Chem. Int. Ed. 2009, 48, 290.
52 Noda, D.; Sunada, Y.; Hatakeyama, T.; Nakamura, M.; Nagashima, H. J. Am. Chem. Soc. 2009, 131, 6078.
53 Although the canonical mechanism has been widely accepted for Pd catalyzed cross coupling reactions, several alternatives have been proposed for the cross coupling reactions based on the rst row transition metal catalysts including Fe, Co, and Ni. See refs. 25f, 26j, 34c, 49, and 50.
54 (a) Nakamura, E.; Mori, S.; Morokuma, K. J. Am. Chem. Soc. 1998, 120, 8273. (b) Mori, S.; Nakamura, E.; Morokuma, K. J. Am. Chem. Soc. 2000, 122, 7294.
55 [Ar 4Fe III][Li(THF) 3]: (a) Alonso, P. J.; Arauzo, A. B.; Forniés, J.; Garcia Monforte, M. A.; Martin, A.; Martinez, J. I.; Menjón, B.; Rillo, C.; Sáiz Garitaonandia, J. J. Angew. Chem. Int. Ed. 2006, 45, 6707. [Me 4Fe II][Li(OEt 2)] 2: (b) Fürstner, A.; Krause, H.; Lehmann, C. W. Angew. Chem. Int. Ed. 2006, 45, 440. Fe F complex: (c) Vela, J.; Smith, J. M.; Yu, Y.; Ketterer, N. A.; Flaschenriem, C. J.; Lachicotte, R. J.; Holland, P. L. J. Am. Chem. Soc. 2005, 127, 7857.
56 The DFT calculations were performed using the B3LYP hybrid functional and the 6 31G basis set. All stationary points were optimized without any symmetry assumptions, and characterized all by normal coordinate analysis at the same level of the geometry optimization. Theoretical studies using DFT method on (0) (II) mechanism for nickel catalyzed cross coupling and related reactions: Reinhold, M.; McGrady, J. E.; Perutz, R. N. J. Am. Chem. Soc. 2004, 126, 5268 and citations therein. See also a recent paper: Yoshikai, N.; Matsuda, H.; Nakamura, E. J. Am. Chem. Soc. 2008, 130, 15258.
57 Because the B3LYP functional has been known to overestimate the
stability of high spin states, we examined several functionals, including the one without a HF exchange term (BP91) and another with a modi- ed admixture of the HF term (B3LYP ), which rendered virtually the same results. Further computational study on the present catalytic cross coupling reactions requires the development of multicongura- tional treatment such as CASSCF caluclations using realistic chemical models, which has been so far impractical. Zein, S.; Borshch, S. A.; Fleurat Lessard, P.; Casida, M. E.; Chermette, H. J. Chem. Phys. 2007, 126, 014105. For how B3LYP and the coefcient of exact exchange admixture in DFT calculation affect relative energies of states of different multiplicity, see: Reiher, M.; Salomon, O.; Hess, B. A. Theor. Chem. Acc. 2001, 107, 48.
58 The rst report on the reaction of aryl suldes: Wenkert, E.; Ferreira W. T.; Michelotti, L. E. J. Chem. Soc., Chem. Commun. 1979, 637.
59 The rst report on the reaction of heteroaryl sulde: Takei, H.; Miura, M.; Sugimura, H.; Okamura, H. Tetrahedron Lett. 1979, 1447.
60 Reviews: (a) Whitham G. H.; Organosulfur Chemistry; Oxford Univ. Press; Oxford, 1995. (b) Dubbaka, S. R.; Vogel, P. Angew. Chem. Int. Ed. 2005, 44, 7674. (c) Luh, T. Y.; Ni, Z. J. Synthesis 1990, 89.
61 The smell of alkanethiols: Node, M.; Kumar, K.; Nishide, K.; Ohsugi, S.; Miyamoto, T. Tetrahedron Lett. 2001, 42, 9207.
62 Selected cross coupling reactions of alkyl aryl suldes: (a) Melzig, L.; Metzger, A.; Knochel, P. J. Org. Chem. 2010, 75, 2131. (b) Kanemura, S.; Kondoh, A; Yorimitsu, H.; Oshima, K. Synthesis 2008, 2659. (c) Leconte, N.; Wuillaume, A. K.; Suzenet, F.; Guillaumet, G. Synlett 2007, 204. (d) Itami, K; Yamazaki, D.; Yoshida, J. J. Am. Chem. Soc. 2004, 126, 15396. (e) Alphonse, F. A.; Suzenet, F.; Keromnes, A.; Lebret, B.; Guillaumet, G. Org. Lett. 2003, 5, 803. (f) Liebeskind, L. S.; Srogl, J. Org. Lett. 2002, 4, 979. (g) Srogl, J.; Liu, W.; Marshall, D.; Liebeskind, L. S. J. Am. Chem. Soc. 1999, 121, 9449. (h) Tiecco, M.; Testaffrri, L.; Tingoli, M. Tetrahedron 1983, 39, 2289.
63 The industrial supply of sulfur: Ober, J. A. U.S. Geol. Surv., Mineral Commodity Summaries, 1998, 166. For archives at USGS, see: http:// minerals.usgs.gov/minerals/pubs/commodity/sulfur/
64 Reactions of dithioacetals with Grignard reagents give olens.: (a) Luh, T. Y. J. Organomet. Chem. 2002, 653, 209. (b) Luh, T. Y. Acc. Chem. Res., 1991, 24, 257.
65 The use of dodecanethiol instead of dodecyl phenyl sulde did not give the alkenylative coupling product 6 but the conventional coupling product, 1 dodecyl 4 methylbenzene (7%), dodecane (24%), and 1 dodecene (27%), respectively.
66 The reaction of 2,2,4,4,6,6 hexamethyl 1,3,5 trithiane, a trimer form of propane 2 thione, with 4 (N,N dimethylamino)phenyl Grignard reagent gave the corresponding alkenylative coupling product, N,N dimethyl 4 (prop 1 en 2 yl)aniline (17%) with recovery of the trithiane (51%), which indicates the intermediacy of thioketone in the present alkenylative coupling reaction.
67 The deprotonation of thiocarbonyl compounds: (a) Nocher, A. M. L.; Metzner, P. Tetrahedron Lett. 1992, 33, 6151. (b) Murase, M.; Yoshida, S.; Hosaka, T.; Tobinaga, S. Chem. Pharm. Bull. 1991, 39, 489.
68 The tautomerization of thiocarbonyl compounds: Zhang, X. M.; Malick, D.; Petersson, G. A. J. Org. Chem. 1998, 63, 5314.
69 Cross couplings of aryl thiolates: (a) Cho, Y. H.; Kina, A.; Shimada, T.; Hayashi, T. J. Org. Chem. 2004, 69, 3811. (b) Swindell, C. S.; Blasé, F. R. Tetrahedron Lett. 1990, 31, 5405.
70 Generation of MgS: Nieto, J. T.; Arévalo, A.; Gutiérrez, P. G.; Ramírez, A. A.; García, J. J. Organometallics 2004, 23, 4534.
71 Addition of Grignard reagents to thioketone: Lin, C. E.; Richardson, S. K.; Wang, W.; Wang, T.; Garvey, D. S. Tetrahedron 2006, 62, 8410.
72 The reaction of naphthalene 2 ylmethanethiol with 3 equivalents of p tolyl Grignard reagent under the present reaction conditions gave the coupling product, 2 (4 methylbenzyl)naphthalene (35%) and the reduced product, 2 methyl naphthalene (27%). For geminal dimethyla- tion of dithioacetals, see: Yang, P. F.; Ni, Z. J.; Luh, T. Y. J. Org. Chem. 2002, 653, 209.
Vol.69 No.11 2011 103 1297
69-1111_Hatakeyama.indd 103 2011/10/20 14:25:56
PROFILE
Takuji Hatakeyama is Assistant Professor of Chemistry at Kyoto University. He was born in Tokyo in 1977. He received his B.Sc. (2000) and D.Sc. (2005) from the University of Tokyo. He joined Prof. Ismagilov group at Chicago University as a postdoctoral fellow in 2005. He became an assistant professor of Professor Nakamura’s group at Kyoto Uni- versity in 2006. He became concurrently a PRESTO researcher of Japan Science and Technology Agency in 2011. His research interests are in the area of synthetic organic chemistry, organometallic chemistry, and computational chemistry.
Kentaro Ishizuka is Post doctoral Fellow of Chemistry at Kyushu University. He was born in Kagoshima in 1980. He received his M.Sc. (2004) and D.Sc. degree (2007) from Kyushu University. He joined Prof. Nakamura group at Kyoto University as a postdoctoral fellow in 2007. He became an assistant professor of Institute of Sustain- ability Science (ISS) at Kyoto University in 2009. He moved to Kyushu University as a post doctoral fellow of Institute for Materi- als Chemistry and Engineering (IMCE) in 2010. His research interests are in the area of synthetic organic chemistry, especially asymmetric synthesis.
Masaharu Nakamura is Professor of Chemi- stry at Kyoto University. He was born in Tokyo in 1967. He received his B.Sc. (1991) from Tokyo University of Science, and his D.Sc. degree (1996) from Tokyo Institute of Technology. He became an assistant professor of Professor Nakamura’s group at the University of Tokyo in 1996, and then was promoted to a lecturer (2002) and an associ- ate professor (2004). During this period, he joined Prof. Jacobsen group at Harvard Uni- versity as a visiting scholar (1999 2000), and then, became concurrently a PRESTO researcher of Japan Science and Technology Agency (2002 2006). In 2006, He moved to Kyoto University as a professor of Interna- tional Research Center for Elements Science, Institute for Chemical Research (ICR). He received the Chemical Society of Japan Award for Young Chemists in 2001. His research eld includes organic reaction, organometallic, and computational/theoretical chemistries, all of which focus on the inven- tion and discovery of new molecular transformations for organic synthesis of the next generation.
69-1111_Hatakeyama.indd 104 2011/10/20 14:25:58

cross coupling reactions catalyzed by iron group metals

Documents