This journal is©The Royal Society of Chemistry 2018 Chem. Commun., 2018, 54, 8885--8888 | 8885

Cite this:Chem. Commun., 2018,

54, 8885

Oximinotrifluoromethylation of unactivatedalkenes under ambient conditions†

Na Wang,‡ab Jian Wang,‡b Yu-Long Guo,b Lei Li,b Yan Sun,b Zhuang Li,b

Hong-Xia Zhang,a Zhen Guo, a Zhong-Liang Li*c and Xin-Yuan Liu *b

An efficient protocol for oximinotrifluoromethylation of unactivated

alkenes was developed via trifluoromethyl radical-induced intra-

molecular remote oximino migration under mild reaction conditions,

providing a wide range of b-trifluoromethylated oximes. Other

fluoroalkyl radicals were also applicable for this transformation.

This method provided access to synthetically challenging medium-

sized ring scaffolds and the 6,7,5-fused lactam skeleton.

Over the past decades, the significance of a trifluoromethyl(–CF3) group in pharmaceuticals and agricultural chemicalshas spurred intensive research in introducing it into organicmolecules.1 Due to its tremendous progress, the radical-mediatedolefin difunctionalization has emerged as one of the most appealingstrategies to simultaneously incorporate a trifluoromethyl groupand an additional functional group into unactivated alkenes(Scheme 1a).1,2 On the other hand, oximes are valuable andversatile building blocks in organic synthesis, which participatein a variety of synthetic transformations, such as nucleophilicaddition, radical reactions, Beckmann rearrangement, etc.,3 andserve as important precursors in the synthesis of hydroxyaminesand amides. Given the significance of both a trifluoromethyl groupand oximes, the oximinotrifluoromethylation of unactivatedalkenes should have great synthetic potential in various areas.However, to the best of our knowledge, this reaction remains agreat challenge probably due to the incompatibility of oximationreagents and trifluoromethyl precursors (Scheme 1a).4

Recently, radical-mediated skeletal reorganization via intra-molecular remote functional group migration has provided an

alternative efficient protocol for olefin difunctionalization.5 Inthis context, our group has developed formyltrifluoromethylationand cyanotrifluoromethylation of unactivated alkenes via intra-molecular remote formyl and cyano migrations, respectively, whileutilizing Togni’s reagent6 as a trifluoromethyl radical precursor(Scheme 1b).5e,f Notably, these protocols require high reactiontemperature probably due to the unfavorable formation of high-energy alkoxyl or alkyliminyl radical intermediates/transitionstates upon the attack of formyl or cyano groups by the incipientalkyl radicals, which arguably limits functional group toleranceto some extent.7 On the other hand, it has been well establishedthat oximes are much better radical acceptors due to thestabilization of the aminyl radical intermediate/transition stateprovided by a lone pair on the adjacent oxygen.3,4 Therefore, wespeculated that the aforementioned olefin oximinotrifluoro-methylation reaction might be realized via a radical-initiatedintramolecular remote oximino migration under mild syntheticconditions. If successful, it would provide an efficient andversatile tool for the synthesis of b-trifluoromethylated oximes.Herein, we report the realization of oximinotrifluoromethylation ofunactivated alkenes via intramolecular radical 1,4- and 1,5-oximinomigration processes (Scheme 1c). Notably, other fluoroalkyl radicals

Scheme 1 Trifluoromethylation of alkenes via radical remote migration.

a College of Materials Science & Engineering, Key Laboratory of Interface Science

and Engineering in Advanced Materials, Ministry of Education, Taiyuan University

of Technology, Shanxi, 030024, Chinab Department of Chemistry and Shenzhen Grubbs Institute, Southern University of

Science and Technology, Shenzhen 518055, China. E-mail: liuxy3@sustc.edu.cnc Academy for Advanced Interdisciplinary Studies, Southern University of Science

and Technology, Shenzhen, 518055, China. E-mail: lizl@sustc.edu.cn

† Electronic supplementary information (ESI) available: Experimental sectionand characterization of compounds. See DOI: 10.1039/c8cc05186k‡ These authors contributed equally to this work.

Received 28th June 2018,Accepted 17th July 2018

DOI: 10.1039/c8cc05186k

rsc.li/chemcomm

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are also applicable for these transformations to allow forexpedient accumulation of various fluoro-containing oximes.More importantly, this strategy also provides a vital platform foraccessing synthetically challenging fluoro-containing benzannu-lated medium-sized rings and a fused 6,7,5-tricyclic ring which isthe core structure of bioactive benzazepinones.8

At first, we examined the reaction of alkenyl oxime 1A andTogni’s reagent 26 with a catalytic amount of CuI (10 mol%) inCH2Cl2 at 60 1C (oil-bath temperature) for the speculatedoximinotrifluoromethylation of unactivated alkenes via a 1,4-oximino migration. To our delight, we obtained the desiredtrifluoromethylated oxime 3A in 84% yield albeit in a relativelylow isomeric ratio (1.9 : 1) (Table 1, entry 1). Next, we found thatthis isomeric ratio was not affected by different copper sources(Table 1, entries 1–5), but was slightly sensitive to differentsolvents (Table 1, entries 1 and 6–10). Fortunately, we observedfurther improvement in this ratio upon lowering the reactiontemperature when conducting the reaction in the optimalsolvent 1,4-dioxane (Table 1, entries 10–12). Thus, the reactionworked the best at ambient temperature to provide trifluoro-methylated oxime 3A in a 17 : 1 isomeric ratio (entry 12).Noteworthy is that the reaction efficiency remained apparentlyintact at decreased temperatures, a phenomenon in agreementwithout initial speculation.

With the optimized conditions in hand, we next evaluatedthe substrate scope (Table 2). As for the tertiary alcohol moiety,para-substituted electron-rich (1B and 1C) and electron-deficient(1D–1F) aryl rings all were well tolerated to afford the desiredproducts 3B–3F in 60–71% yields under the mild reactionconditions. Similarly, aryl rings with meta- (3G) or ortho-chloride(3H) provided comparable results with the para-substitutedone (3E), demonstrating no apparent influence of substitutionpositions on the reaction efficiency. Bicyclic naphthyl as well as

heteroaromatic furyl and thienyl rings were also suitable for thereaction to deliver 3I–3K in 69–71% yields. Notably, switchingthis aromatic ring to an alkyl group in 1L still led to theformation of the desired product 3L albeit with a slightlydiminished yield. With regard to the oxime moiety, additionalmethyl-substitution in 1M and 1N was tolerated to differentextents to generate 3M and 3N in 79% and 25% yields,respectively. These results again clearly indicate that the currentoximino migration is more facile than our previously reportedcarbonyl migration since a similar substitution resulted in failedmigration in that case.5e Meanwhile, substrate 1O possessing a para-methoxyl benzyl (PMB) group on oxime also worked well to providethe desired trifluoromethylated oxime 3O in 80% yield. In termsof the chain length in-between, the radical-initiated 1,5-oximinomigration process was also operational under the standardreaction conditions to give 3P in 69% yield.

To further increase the applicability of this protocol in fluorinechemistry, we expanded the reaction scope to cover other fluoro-containing radical precursors (Table 3). Recently, visible-light-mediated photoredox catalysis has become a useful tool for thegeneration of various radical species under mild conditions.9 Inparticular, fluoroalkyl sulfonyl chlorides have proved to be idealprecursors for the formation of fluoroalkyl radicals via extrusion ofsulfur dioxide under visible light irradiation.10 We thus treatedsubstrate 1A with trifluoromethanesulfonyl chloride10b in thepresence of photocatalyst [Ir(ppy)2(dtbbpy)]PF6 (1 mol%) aswell as 2 equivalents of Na2HPO4 under visible light initiation.

Table 1 Screening of reaction conditionsa

Entry Cat. Solvent Tempb. (1C) Yieldc (E/Z)

1 CuI CH2Cl2 60 84% (1.9 : 1)2 CuBr CH2Cl2 60 82% (1.9 : 1)3 CuCl CH2Cl2 60 84% (1.8 : 1)4 CuOAc CH2Cl2 60 80% (2.0 : 1)5 CuCN CH2Cl2 60 82% (2.2 : 1)6 CuI EtOAc 60 86% (3.1 : 1)7 CuI DMF 60 85% (4.7 : 1)8 CuI DCE 60 83% (1.9 : 1)9 CuI CH3CN 60 85% (2.4 : 1)10 CuI 1,4-Dioxane 60 84% (5.0 : 1)11 CuI 1,4-Dioxane 40 85% (7.5 : 1)12 CuI 1,4-Dioxane 25 89% (17 : 1)d

a Unless otherwise noted, the reaction was performed with 1A (0.1 mmol),Togni’s ester 2 (0.12 mmol), and Cu(I) (10 mol%) in solvent (1.0 mL) for24 h. b Oil-bath temperature. c Yields and isomeric ratios of E/Z weredetermined by crude 19F NMR spectroscopy using PhCF3 as an internalstandard. d Isolated yield for the major (E)-isomer: 81%.

Table 2 Substrate scope for oximinotrifluoromethylation reactiona

a Reaction conditions: 1 (0.2 mmol), 2 (0.24 mmol), and CuI (0.02 mmol)in 1,4-dioxane (2.0 mL) at 25 1C, for 24 h. PMB = CH2C6H4p-OMe.

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To our delight, the reaction afforded the desired trifluoromethylatedoxime 3A in 82% yield, comparable with that obtained using Togni’sreagent 2. Meanwhile, difluoromethyl and perfluorobutyl radicals10a

were also successfully generated and applied to the oximinomigration process to produce the desired fluoroalkylated oximes5 and 6 in 72% and 58% yields, respectively, by the similarprotocols. More encouragingly, cheap BrCF2CO2Me (7)11 was alsoapplicable in this strategy to give the difluoroalkylated oxime 8 in71% yield.

Medium-sized cyclic compounds are basic structural motifsin many naturally occurring and biologically active molecules.12

Their synthesis remains a formidable challenge due to the unfavor-able transannular interactions and entropic and/or enthalpicfactors.13 Encouraged by the above success, we thus switchedour efforts toward the synthetically challenging medium-sizedrings. To this end, we envisioned that a ring-expansion strategyvia intramolecular 1,4- or 1,5-oximino migrations might beoperational and designed the alkenyl cyclic oximes 9 as thesubstrates. As expected, substrate 9A featuring a cyclopentanoneoxime motif reacted smoothly with Togni’s reagent 2 in thepresence of CuCN to afford the trifluoromethylated eight-membered oxime 10 in 82% yield (isomeric ratio = 1.7 : 1) at roomtemperature (Table 4). In addition, substrates 9B and 9C bearingsix- and seven-membered cyclic oxime groups both worked wellto afford trifluoromethylated nine- and ten-membered cyclicoximes 11 and 12 in 76% and 77% yields, respectively, in high

isomeric ratios. Furthermore, allylbenzene derivative 9D alsounderwent the reaction smoothly to provide the desired product13 in 67% yield. Overall, this trifluoromethyl radical-initiatedring expansion strategy provides a useful tool for the synthesisof a range of synthetically challenging eight- to ten-memberedmedium-sized cyclic scaffolds.

The obtained trifluoromethylated oximes can serve as aconvenient handle to provide other useful skeletons by furthertransformations. For example, the PMB group of oxime 3O wassuccessfully removed upon treatment with AlCl3 to release thefree trifluoromethylated oxime 14 in 57% yield (Scheme 2a). Inaddition, the nine-membered cyclic oxime 11 was treated withNaOMe to generate 6,7,5-fused lactam 15 in 40% yield, which isthe core structure of bioactive benzazepinones (Scheme 2b).8

To examine the scalability of this reaction, we carried out thereaction of 1F on a 1.5 mmol scale and obtained the desiredproduct 3F in comparable yield with that obtained on a 0.2 mmolscale (Scheme S1 in the ESI†). To get insight into the reactionmechanism, the control experiment with radical inhibitor 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) was performed with 1A and2 under the otherwise standard conditions which displayed almostcomplete inhibition. This result suggests that a radical processmight be involved (Scheme S2 in the ESI†).

Based on the above result and our previous research,5d–g weproposed a plausible mechanism for the oximino migrationprocess (Scheme 3). Togni’s reagent 2 and Cu(I) species firstunderwent a single-electron-transfer (SET) process to generate atrifluoromethyl radical and Cu(II). Next, the trifluoromethylradical was selectively added to the alkene group of substrate1 to generate transient alkyl radical intermediate I, whichsubsequently underwent an intramolecular 5/6-exo cyclization toprovide oxyaminyl radical II. The following selective b-scission ofintermediate II afforded a lower-energy neutral ketyl radical III,14

thus providing a strong driving force for the oximino migrationprocess. A further single-electron oxidation of intermediate III by

Table 3 Substrate scope for versatile fluoroalkylation reactions

a Reaction conditions: 1A (0.2 mmol), 4 (0.30 mmol), [Ir(ppy)2(dtbbpy)]PF6(0.002 mmol), and Na2HPO4 (0.4 mmol) in 1,4-dioxane (2.0 mL) at 25 1C for5 h. b 1A (0.2 mmol), 7 (0.3 mmol), [Ir(ppy)2(dtbbpy)]PF6 (0.002 mmol) andNa2HPO4 (0.4 mmol) in 1,4-dioxane (2.0 mL) at 25 1C for 5 h.

Table 4 Substrate scope for the synthesis of medium-sized ringsa

a Reaction conditions: 1 (0.2 mmol), 2 (0.24 mmol), and CuCN (0.02 mmol)in 1,4-dioxane (2.0 mL) at 25 1C for 24 h.

Scheme 2 Synthetic applications.

Scheme 3 Plausible mechanism.

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either Togni’s reagent 2 or Cu(II) species delivered the desiredproduct 3.

In summary, we have successfully developed an efficient1,2-oximinotrifluoromethylation of unactivated alkenes via anintramolecular remote oximino migration process triggered bythe addition of trifluoromethyl radicals to alkenes. The reactiondistinguishes itself from our previously reported cyano andformyl migrations by invoking a more stable oxyaminyl radicalintermediate/transition state, which has led to much milderreaction conditions. Other fluoroalkyl radicals were also applicablefor the transformation to deliver a diverse array of b-fluoroalkylatedoximes. All these results render this strategy synthetically versatileand useful for fluorine chemistry. More importantly, this strategyalso provides a valuable platform for constructing syntheticallychallenging medium-sized cyclic scaffolds as well as polycyclicskeletons, showcasing its great synthetic potential in organicsynthesis and related fields.

Financial support from the National Natural Science Foundationof China (No. 21722203 and 21572096), Shenzhen special fundsfor the development of biomedicine, Internet, new energy,and new material industries (JCYJ20170412152435366 andJCYJ20170307105638498), and Shenzhen Nobel Prize ScientistsLaboratory Project (C17213101) is greatly appreciated.

Conflicts of interest

There are no conflicts to declare.

Notes and references1 For selected reviews, see: (a) T. Furuya, A. S. Kamlet and T. Ritter,

Nature, 2011, 473, 470; (b) J. Nie, H.-C. Guo, D. Cahard and J.-A. Ma,Chem. Rev., 2011, 111, 455; (c) O. A. Tomashenko and V. V. Grushin,Chem. Rev., 2011, 111, 4475; (d) L. Chu and F.-L. Qing, Acc. Chem.Res., 2014, 47, 1513; (e) J. Charpentier, N. Fruh and A. Togni, Chem.Rev., 2015, 115, 650; ( f ) C. Ni, M. Hu and J. Hu, Chem. Rev., 2015,115, 765; (g) X.-H. Xu, K. Matsuzaki and N. Shibata, Chem. Rev.,2015, 115, 731; (h) X. Yang, T. Wu, R. J. Phipps and F. D. Toste,Chem. Rev., 2015, 115, 826; For selected recent examples, see:(i) L. Li, X. Mu, W. Liu, Y. Wang, Z. Mi and C.-J. Li, J. Am. Chem.Soc., 2016, 138, 5809; ( j ) O. Yao, X.-H. Xu and F.-L. Qing, Angew.Chem., Int. Ed., 2018, 57, 6926.

2 For selected reviews, see: (a) P. Chen and G. Liu, Synthesis, 2013,2919; (b) H. Egami and M. Sodeoka, Angew. Chem., Int. Ed., 2014,53, 8294; (c) E. Merino and C. Nevado, Chem. Soc. Rev., 2014,43, 6598; (d) J. Xu, X. Liu and Y. Fu, Tetrahedron Lett., 2014,55, 585; (e) A. Studer and D. P. Curran, Angew. Chem., Int. Ed.,2016, 55, 58; ( f ) Y. Zeng, C. Ni and J. Hu, Chem. – Eur. J., 2016,22, 3210; (g) Y. Tian, S. Chen, Q.-S. Gu, J.-S. Lin and X.-Y. Liu,Tetrahedron Lett., 2018, 59, 203; For selected recent examples, see:(h) A. T. Parsons and S. L. Buchwald, Angew. Chem., Int. Ed., 2011,50, 9120; (i) X. Wang, Y. Ye, S. Zhang, J. Feng, Y. Xu, Y. Zhang andJ. Wang, J. Am. Chem. Soc., 2011, 133, 16410; ( j ) J. Xu, Y. Fu,D.-F. Luo, Y.-Y. Jiang, B. Xiao, Z.-J. Liu, T.-J. Gong and L. Liu, J. Am.

Chem. Soc., 2011, 133, 15300; (k) Y. Cheng, C. Muck-Lichtenfeld andA. Studer, J. Am. Chem. Soc., 2018, 140, 6221.

3 For selected reviews, see: (a) A. G. Fallis and I. M. Brinza, Tetrahedron, 1997,53, 17543; (b) G. K. Friestad, Tetrahedron, 2001, 57, 5461; (c) H. Miyabe,M. Ueda and T. Naito, Synlett, 2004, 1140; (d) K. Sunggak, Adv. Synth. Catal.,2004, 346, 19; (e) J. C. Walton, Acc. Chem. Res., 2014, 47, 1406.

4 For selected examples, see: (a) S. Kim, I. Y. Lee, J.-Y. Yoon andD. H. Oh, J. Am. Chem. Soc., 1996, 118, 5138; (b) E. Godineau andY. Landais, J. Am. Chem. Soc., 2007, 129, 12662; (c) B. Ovadia,F. Robert and Y. Landais, Org. Lett., 2015, 17, 1958.

5 For selected reviews, see: (a) J. R. Donald and W. P. Unsworth, Chem. –Eur. J., 2017, 23, 8780; (b) W. Li, W. Xu, J. Xie, S. Yu and C. Zhu, Chem.Soc. Rev., 2018, 47, 654; For selected recent examples, see:(c) W. Kong, M. Casimiro, E. Merino and C. Nevado, J. Am. Chem.Soc., 2013, 135, 14480; (d) L. Li, Z.-L. Li, F.-L. Wang, Z. Guo,Y.-F. Cheng, N. Wang, X.-W. Dong, C. Fang, J. Liu, C. Hou, B. Tanand X.-Y. Liu, Nat. Commun., 2016, 7, 13852; (e) Z.-L. Li, X.-H. Li,N. Wang, N.-Y. Yang and X.-Y. Liu, Angew. Chem., Int. Ed., 2016,55, 15100; ( f ) N. Wang, L. Li, Z.-L. Li, N.-Y. Yang, Z. Guo,H.-X. Zhang and X.-Y. Liu, Org. Lett., 2016, 18, 6026; (g) L. Li,Z.-L. Li, Q.-S. Gu, N. Wang and X.-Y. Liu, Sci. Adv., 2017,3, e1701487; (h) Z. Wu, R. Ren and C. Zhu, Angew. Chem., Int. Ed.,2016, 55, 10821; (i) Z. Wu, D. Wang, Y. Liu, L. Huan and C. Zhu,J. Am. Chem. Soc., 2017, 139, 1388; ( j ) Y. Xu, Z. Wu, J. Jiang, Z. Keand C. Zhu, Angew. Chem., Int. Ed., 2017, 56, 4545; (k) J. Yu, D. Wang,Y. Xu, Z. Wu and C. Zhu, Adv. Synth. Catal., 2018, 360, 744;(l ) X. Tang and A. Studer, Chem. Sci., 2017, 8, 6888; (m) X. Tangand A. Studer, Angew. Chem., Int. Ed., 2018, 57, 814.

6 E. Patrick, G. Sebastian and T. Antonio, Chem. – Eur. J., 2006,12, 2579.

7 For selected examples, see: (a) A. L. J. Beckwith, D. M. O’Shea,S. Gerba and S. W. Westwood, J. Chem. Soc., Chem. Commun., 1987,666; (b) R. A. Walton and B. Fraser-Reid, J. Am. Chem. Soc., 1991,113, 5791; (c) A. L. J. Beckwith and K. D. Raner, J. Org. Chem., 1992,57, 4954; (d) T. Kawamoto, S. J. Geib and D. P. Curran, J. Am. Chem.Soc., 2015, 137, 8617.

8 J. Frackenpohl, I. Heinemann, T. Mueller, G. Bojack, J. Dittgen, P. VonKoskull-Doering, D. Schmutzler, M. J. Hills and J. P. R.-S. Moreno, PCTInt. Appl., WO2014037313A1, 2014.

9 For selected reviews, see: (a) T. P. Yoon, M. A. Ischay and J. Du, Nat.Chem., 2010, 2, 527; (b) J. M. R. Narayanam and C. R. J. Stephenson,Chem. Soc. Rev., 2011, 40, 102; (c) J. Xuan and W.-J. Xiao, Angew.Chem., Int. Ed., 2012, 51, 6828; (d) C. K. Prier, D. A. Rankic andD. W. C. MacMillan, Chem. Rev., 2013, 113, 5322; (e) N. A. Romeroand D. A. Nicewicz, Chem. Rev., 2016, 116, 10075; For selected recentexamples, see: ( f ) K. Matsuzaki, T. Hiromura, E. Tokunaga andN. Shibata, ChemistryOpen, 2017, 6, 226; (g) K. Matsuzaki,T. Hiromura, H. Amii and N. Shibata, Molecules, 2017, 22, 1130.

10 (a) X.-J. Tang, C. S. Thomoson and W. R. Dolbier, Org. Lett., 2014,16, 4594; (b) X.-J. Tang and W. R. Dolbier, Angew. Chem., Int. Ed.,2015, 54, 4246.

11 (a) P. Xu, W. Li, J. Xie and C. Zhu, Acc. Chem. Res., 2018, 51, 484;(b) J.-W. Gu, Q.-Q. Min, L.-C. Yu and X. Zhang, Angew. Chem., Int. Ed.,2016, 55, 12270; (c) During this part of experiments, Zhu’s groupreported a visible-light-irradiated imino migration process, wheresimilar reagents were used as the radical precursors. See: ref. 5k.

12 (a) E. M. Simmons and R. Sarpong, Nat. Prod. Rep., 2009, 26, 1195;(b) J. Xu, F. Ji, J. Kang, H. Wang, S. Li, D.-Q. Jin, Q. Zhang, H. Sunand Y. Guo, J. Agric. Food Chem., 2015, 63, 5805.

13 (a) W. Zhao, Z. Li and J. Sun, J. Am. Chem. Soc., 2013, 135, 4680;(b) L.-C. Yang, Z.-Q. Rong, Y.-N. Wang, Z. Y. Tan, M. Wang andY. Zhao, Angew. Chem., Int. Ed., 2017, 56, 2927.

14 (a) Y.-R. Luo, Comprehensive Handbook of Chemical Bond Energies, CRCPress, 2007; (b) Y. Qin, L. Zhu and S. Luo, Chem. Rev., 2017, 117, 9433.

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