vy m. dong, jinquan yu and their research work. professional experience university of toronto:...
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Vy M. Dong , Jinquan Yu and their research work
Professional ExperienceUniversity of Toronto:Associate Professor, July 2010 to present.Assistant Professor, July 2006 to June 2010.
National Institutes of Health Postdoctoral Fellow at the University of California at Berkeley: December 2003 to May 2006. Organometallic and supramolecular chemistry with Robert Bergman and Kenneth Raymond
Graduate Student at UC Berkeley and the California Institute of Technology:July 1998 to October 2003. Doctoral studies in organic synthesis with David MacMillan Undergraduate Research Assistant at the University of California at Irvine:June 1998. Undergraduate thesis on the tethered Biginelli condensation with Larry Overman.
Vy M. Dong
Education experience:Harvard University - Cambridge, MA, USA• Postdoctoral Fellow Supervisor: E. J. Corey February 2001 to May 2002University of Cambridge - Cambridge, UK• Junior Research Fellow (JRF) of St. John's College October 1999 to October 2003University of Cambridge - Cambridge, UK• Ph.D. in Chemistry Supervisor: Jonathan B. Spencer (also Mattew Gaunt’s PhD Supervisor) October 1994 to September 1999Guangzhou Institute of Chemistry - Guangzhou, China• M.Sc. in Chemistry Supervisor: S.-D. Xiao （萧树德 ） September 1988 to July 1990Shanghai Institute of Organic Chemistry - Shanghai, China• Coursework for M.Sc. degree September 1987 to July 1988East China Normal University - Shanghai, China• B.Sc. in Chemistry Top 5% on national examination for admission to SIOC Supervisors: L.-X. Dai and B.-Q. Wu September 1982 to July 1987
Jinquan Yu( 余金权 )
Jonathan B. Spencer (1960-2008).
Positions:The Scripps Research Institute - La Jolla, CA, USA• Professor of Chemistry August 2010 to Present• Associate Professor, Department of Chemistry July 2007 to August 2010
Brandeis University - Waltham, MA, USA• Assistant Professor, Department of Chemistry March 2004 to June 2007
University of Cambridge - Cambridge, UK• Royal Society Research Fellow October 2003 to February 2004
Guangzhou Institute of Chemistry - Guangzhou, China• Teaching and Research Assistant in Organic Chemistry October 1990 to September 1994
Dong’s research work1.Rh(I) complexes to activate the C-H bond of aldehydes
History of Hydroacylation
H
R ORR O
H
R
Olefin Hydroacylation
O
H COOMe
O
COOMe
stoichiometric amount of Wilkinson's catalyst
The reaction was discovered by Kiyoshi Sakai in 1972 as part in a synthetic route to certain prostanoids( 前列腺素 ). The first catalytic application was reported by Roy G. Miller in 1976
Tetrahedron Lett. 1972,13,1287-1290
R1
O
R1Rh(PPh3)3Cl
DCM,r.t.48h
O
R2
O
R2
OR
H
RhCl(PPh3)3 (<1 eq)H
R
Tsuji-Wilkinson decarbonylation reaction
benzene,reflux
R
O
Cl RCl
Rh(PPh3)3Cl
DCM,r.t.48h
Tsuji, J.; Ohno, K, Tetrahedron Lett. 1965, 3969-3971
Tsuji, J.; Ohno, K, J. Am. Chem. Soc. 1968, 90, 9-107
Chem. Lett. 1974,,215-216
R XR
PdXPd(0)complexe(catalytic) Nu-H or Nu-
R Nu
Tsuji-Trost reaction Tetrahderon Lett.,1965,4387-4388
Wacker-Tsuji oxidation
Organic Syntheses, Coll. Vol. 7, p.137
n-C8H17
PdCl2,CuCl,O2
DMF,H2OOn-C8H17
Hydroacylation as an asymmetric reaction was first demonstrated by James and Young in 1983 (kinetic resolution) and by K. Sakai (Kyushu Univ.) (true asymmetric synthesis) in 1989
O0.1eq RhCl(PPh3)3
CHCl3/ClCH2CH2Cl
H
O
72%
J. Am. Chem. Soc., 1976,98,1281–1283
Tetrahedron Lett., 1989,30,6349-6352 J. Chem. Soc., Chem. Commun., 1983, 1215-1216
Ph2PPPh2
O
Ph
MePh
Me
O52%eeracemic
[RhL2]Cl
160C,10 h
n-BuO
O
n-Bu73%ee
N
Boc
PPh2
Ph2P
[Rh(COD)]2Cl
RhⅠH
RO
RhIIIH
O R
R'
R'
RhH
O R
Rh
O R
R'
R O
H
R'
acyl-Rh(III) intermediates
RH+CO
O
O
CHO
TBSO
OPMB
O
TBSO
OPMB
[RhCl(COD)]2,dppp,xylene,reflux
(+)-Laurenyne by Robert K. Boeckman(Univ. Rochester/Associate Editor for JOC) 2002
R H
O
R [RhIII]
O OC[RhI]
[RhI]
HR [RhIII]
CO
H
RH
-CO
retro-CO-insertion
Rh(I) planar squareRh(III) octahedron
Zengming Shen and Vy M. Dong* J. Am. Chem. Soc., 2008, 130, 2916-2917
conventional strategies such as Corey-Nicolaou’s PySSPy and Yamaguchi’s acid chloride
Corey-Nicolaou's PySSPy method was discribed by Corey and Nicolaou in 1974
O
OH
OH
PyS-SPy,PPh3
rt
O
S
OH
N
One pot, two-step reaction: the synthesis of the thioester at roomtemperature and the lactonisation under reflux.
O
S
O-
NH
reflux
O
S
O-
NH
O
ONH
OO=PPh3
Corey, E. J.; Nicolaou, K. C. J. Am. Chem. Soc. 1974, 96, 5614.
O
OH
OH
Cl Cl
COCl
Cl
NEt3,THF
O
O
OH Cl
Cl
Cl
O
The Yamaguchi reagent, 2,4,6-trichlorobenzoyl chloride, discovered in 1979
slow addition anhydride to a refluxing solution of DMAP (cat) in toluene
O
N
OH
N
O
O
Yamaguchi, M. Bull. Chem. Soc. Jpn. 1979, 52, 1989.
Ketone Hydroacylation
O
O
H
O
RhI
C-H activation R
O
RhIII HR
O
H
R' R''
O
Tishchenko-type
R
O
RhIII OR'
R''H
R
O
OR'
R''H
benzoin-type
R
O
R'R''
ORhIII
H
R
O
R'R''
OH
decarbonylation
RHChelation has been proposed to stabilize Rh(III)-acyl intermediates and suppress decarbonylation
The coordinating ability of the ether-oxygen can help suppress decarbonylation and facilitate hydroacylation.
Through the screening of various chiral diphosphine ligands, they found that the relation between phosphine basicity and catalyst selectivity
2 PhCHOBnONa
50-60°C,4h Ph OBn
OTishchenko reaction 季先科反应
J. Russ. Phys. Chem. Soc. 1906, 38, 355
O
BnO
OBn
O-
HO
OBn
O
H
O
Ph
H
Ph OBn
O
O
O
H
R
OO
O
O
RH
[Rh(R)-DTBM-SEGPHOS]BF4
ee up to 99%the least basic phosphine (R)-Ph-MeOBIPH
more basic and sterically encumbering:(R)-Ar-MeOBIPHEP
(S,S)-BDPP\(R,R)-Me-Duphos\(R,R)-Me-BPE(the most basic ligand)affording sluggish reactivity
Zengming Shen, Tom K. Wooand* Vy M. Dong*J. Am. Chem. Soc. 2009, 131, 1077
Mechanistic Insight
The turnover-limiting step: insertion of the ketone C=O bond to the rhodium hydride via TS A
The ether oxygen is coordinated to Rh, and this coordination is critical for promoting insertion over competitive decarbonylation.But this protocol is limited in scope to ketoaldehydes bearing an ether linkage!
J. Am. Chem. Soc. 2009, 131, 15608–15609
H
O
O
O
O
H
O
H
Counterion effects on reactivity: catalysts with more strongly coordinating counterions gave better selectivity for hydroacylation over decarbonylation
The reason of choosing AgNO3 as the optimal additive is that nitrate is less strongly coordinating than Cl (giving shorter reaction times) but coordinating enough to suppress decarbonylation and assist in enantioinduction
H
O
O
R'
O
O
HR'
R R
5miol%[Rh(cod)Cl]25mol%DuanPhos
5mol%AgNO3toluene,100°C
The appropriate choice of counterion was crucial in suppressing decarbonylation and controlling enantioselectivity
Counterions’ coordinating strengths:SbF6- < BF4- < -OTf <-OMs<NO3- < Cl-
O
O
n-Bu
This phthalide is responsible for the flavor of celery, and its racemate was in phase-III clinical trials for treating stroke
97ee%
Chem. Sci. 2011, 2,407-410
The presence of a nitrogen atom not only promotes faster reactivity but also suppresses decarbonylation completely.
N
H
O
MeO
R N
OO
Me
R
H
NMe
O
R
H
decarbonylation
not observed
[Rh(R)-DTBM-SEGPHOS]BF4
Rh-Catalyzed Intramolecular/ Intermolecular Olefin Hydroacylation
J. Am. Chem. Soc. 2009, 131, 6932. Formation of medium-sized ring heterocyclic ketone
Coordination of X to Rh helps promoting olefin hydroacylation over olefin isomerization, aldehyde decarbonylation, and catalyst decomposition
Regioselectivity would depend on the catalyst choice and substrate structure (i.e. X, tether length, and olefin substitution)
Challenge: regio-selectivity
H
O
O
O
O
R R
5mol%[Rh((R,R)-MeDuPHOS)]BF4
15:1 selectivity over its eight-membered-ring regioisomer>85% yield,>95%ee
H
CH2
O
H2C
O
no observable hydroacylation product
H
S
O change S to CH2
If reductive elimination were turnover-limiting in our case, D would be scrambled into the α-position of 11-D. However, we observed that products 10-D and 11-D had D at only the β-position. This lack of D scrambling suggests that reductive elimination is not the turnover-limiting step in our catalytic system.
J. Am. Chem. Soc. 2010, 132, 16330–16333
Challenge was still in regiocontrolWhile reactive in Rh-catalyzed intermolecular hydroacylation,terminal olefins tend to give achiral, linear products or mixtures of regioisomers
Bolm, C. Adv. Synth. Catal. 2007, 349, 1185.
OH
CHO [Rh(acac)(C2H4)2]
Ligand
OH O
O
OP N
(R)-MonoPhos
H. Suemune（ Kyushu Univ） , J. Org. Chem. 2004, 69, 1144-1150
CHO
OH
R
SR''R'
OH
R
O SR''
R'
[Rh(COD)Cl]2(R)-SIPHOS-PE
K3PO4,CH2Cl2
O
OP N
Ph
Ph
> 20:1 regiodselectivityup to 97%ee
1a:salicylaldehyde
J. Am. Chem. Soc. 2010, 132, 16354–16355
Challenge: In general, intermolecular hydroacylation is difficult to achieve due to competing pathways such as decarbonylation and catalyst decomposition
RO
H
H
HR1
R2H
R1R2
OR
strain energy-release hydroacylation
CHO
OH H
HMe
Ph
1A phenolic oxygen is known to coordinate to Rh and promote hydroacylation
H
HMe
Ph
OPh
H
HMe
Ph
OPh1A
CHO
OH H
HMe
Ar'
H
HMe
Ar'
OAr
R5mol%RhJoisPhos
>95%ee,up to 20:1 d.r
2.Palladium-Catalyzed C–H Bond Functionalization first intermolecular palladium-catalyzed transformations of sp2C-H bonds to C-SJ. Am. Chem. Soc. 2009, 131, 3466–3467
Chelation-assisted strategyPervious work: sp2 C-H bonds to C-O, C-X, C-C, and C-N (Yu, Sanford and Ellman’s work)
DG
RArSO2Cl
Pd(CH3CN)2Cl2
K2CO3,1,4-dioxane,120°C
DG
R
O2S
Ar
N NN Ph N
OMeR
Angew. Chem. Int. Ed. 2011, 50, 932 –934The first direct observation of C-S bond-forming reductive elimination from Pd (IV) complexes; the first Pd (IV) complexes containing a Pd-SO2R bond
These results support the feasibility of palladium-catalyzed sulfonylation and desulfitative C-C cross-couplingreactions through a Pd (II)- Pd (IV) catalytic cycle
Chem. Sci., 2010, 1, 331–336
Using sodium persulfate, a nontoxic, environmentally benign, and easy-to-handle oxidant
5mol%Pd(OAc)2
TFA(0.5mmol),K2S2O8(1.5mmol)r.t,24h
15mmol 1.0mmol0.25mmol
selectivity:>95%TON=5.0
Ruoshi Li, Li Jiang, and Wenjun Lu*, Organometallics, 2006, 25 ,5973-5975
Synlett. 2011, in pressInvited contribution in honor of Xiyan Lu and Li-Xin Dai
R
N
O
O
H Ar-H
cat. Pd(OAc)2
TFA,K2S2O8
R
N
O
O
Ar
Tetrahedron, 2009, 65, 3062–3068
Nitrosoalkene and vinylnitrene represent two important intermediates that have been relatively elusive and underutilized for C–N bond formation
3.Othersa. Ru-catalyzed activation of sp3 C–O bonds
Chem. Sci. 2011, 2,544
Direct insertion into electron-rich bonds such as typically insert ethereal C–O bonds
Kakiuchi's work: J. Am. Chem. Soc., 2003, 125, 1698-1699J. Am. Chem. Soc., 2004, 126, 2706-2707.
RO
R'
OMe [Ru]
O
R'
RuOMe
RR''-BY2 O
R'
R''R
XN
Y
O
R
[Ru]X
N
Y
O
Ru
R
XN
Y
O
R
X=CH,NY=CH,N
73 substratesup to 99% yield
A selective intramolecular alkyl transfer process.
This observation suggests that reversible sp3 C–H bond activation is taking place
b. Negishi cross-coupling between organozinc reagents and CO2J. Am. Chem. Soc. 2008, 130, 7826–7827
Aresta's complex NiCy3P
Cy3P O
C
O
J.Chem.Soc.,Chem.Commun.1975,15, 636.
the first metal-CO2 complex to be isolated andcharacterized
X NiXNi(0)
X
Ni(0)
NiX
O Ni ONi(0)
R
O
OAr
Ni(0)
R
O
Ni OAr
Ni(COD)2Ni(PR3)4
X
O
O
Ni(0)
Ni
X
O
OX=O,S,N-R/Ar
CH2
CH2L2Ni NiL2
NiL4
H2L2Ni
H
H L2NiH
H
Takuya Kurahashi and Seijiro Matsubara(Kyoto Univ.)
A. Yamamoto, Organometalic.,1985,4,1130
T. Jamison(MIT)
Ni1 atm CO
313KNi(CO)4 Ni(CO)3+CO
Shin-Ichi Ikeda(Nagoya City Univ.)
NiXNuclephilic
Mond nickel
PdXElectrophilic
J. Am. Chem. Soc. 2008, 130, 6058–6059
ZnBr COOHFG FG
1.
2.1M HCl
5mol %[Ni(PCy3)2]2(N2),1 atm CO2
ZnBr COOH
FG FG1.
2.1M HCl
5mol %Pd(OAc),10 mol% PCy3,1 atm CO2
FG=-OR,-Cl,-CN,-F,-Ac,-COOMe
Work of Iwasawa (Tokyo Institute of Technology)
J. Am. Chem. Soc. 2006, 128, 8706
基本原理：C-H 键直接与 Pd 发生氧化加成(top) electrophilic metalation of the aromatic C–H bond pathway （ SAr
E ）(bottom) Concerted proton transfer metallation pathway
H
PdX Y
X=CO32-,RCO2
-,halideY=aryl or X
H
PdXY
Pd
HX
Y
PdY
HX
DG
H
1. 杂原子的配位定位作用，同时使 C-H 键更易活化2.Various E+
N
HPd OAc
OO
N
HPd OAc
OO
N
HPd OAc
OO
H
H
cyclopalladation
K. Fagnou,Science ， 2007,316,1172
Fujiwara-type reaction
早期研究 : 始于 C(sp2)-H 键的烯化I Moritani; Y Fujiwara. Tetrahedron Lett. 1967, 8, 1119.
HPh
cat. Pd(OAc)2oxidant
TFA
co-sovent
Drawback:1 使用大大过量的芳烃（一部分作为溶剂）2 缺少区域选择性控制
Y. Fujiwara, I. Moritani, J. Am. Chem. Soc. 1969,91,7166
Ar H R1 R2R1 R2
Ar H
TFA
Pd(OAc)2
r.t10mmol 5mmol
highly electrophilic cationic species: Pd(O2CCF3)+
Y Fujiwara ,Science, 2000, 287, 1992
One vinyl H or D in all adducts was mainly from the solvent acid, which presumably results from the protonation of vinyl-Pd complex IMc by TFA-d1 or TFA
The involvement of s-aryl-Pd complexes IMa has been confirmed by the 1H NMR spectrum from the disappearance of the aryl H of 1 in the reaction with l eq of Pd(OAc)2 in TFA in a few minutes at room temperature.
The fact that the hydroarylation reaction failed in other solvents such as acetic acid indicates the necessity of TFA for the formation of cationic Pd(II) species and for the protonation of a vinyl-Pd intermediate IMc to complete the catalytic cycle.
X. Lu, G. Zhu, S. Ma, Tetrahedron Lett. 33, 7205 (1992).
A possible mechanism would be the electrophilic attack of the aromatic C–H bond by cationic Pd(II) species to form IMa followed by coordination of alkyne to give IMb. A trans insertion of C–C triple bonds to the s-aryl-Pd bond (23–25) results in IMc, and 1/1 arene/alkyne adduct would be released from Pd(II) (24) upon protonation of IMc
后来通过引入导向基团，提高区域选择性Masahiro Miura ,J. Org. Chem.,1998,63,5211–5215
COOH
COOn-Bu
10 mol%Pd(OAc)210 mol%Cu(OAc)2
DMF,120C,7hO
O
COOn-Bu42% yield
air
HN
OCOOn-Bu
2mol% Pd(OAc)21eq BQ
5 eq TsOHHOAc,20C,24h
HN
O
COOn-Bu
J. Am. Chem. Soc., 2002, 124, 1586-1587
C(sp2)-H 键和 C(sp3)-H 键的芳基化和烷基化
Organometallics, 2006, 25 ,5973-5975
Ar-H+Ar’-H→Ar’-Ar 比较困难Ar-H 和 Ar’-H 很容易发生自身偶联，减少交叉偶联产物
K. Fagnou, Science, 2007,316,1172
3 eq. Cu(OAc)2 and arene (~30 eq)
homo-coupling VS cross-coupling
H
PdX Y
X=CO32-,RCO2
-,halideY=aryl or X
H
PdXY
Pd
HX
Y
PdY
HX
palladium(II) complexes can react via SArE with good selectivity for electron-rich arenes
J. Am. Chem. Soc.,2006,128,1066–1067
Yu’s research work
Metal-catalyzed carbon-carbon and carbon-heteroatom bond forming reactions based on C-H activation
Pd(II)/Pd(IV), Pd(II)/Pd(0) and Cu(II)/Cu(0) redox systems
1.Activation of sp2 C-H bond
2.Activation of sp3 C-H Bonds
1.Activation of sp2 C-H bond
O
O(NH)R
H H
COOH
HOH
R''R'
HNHR
R''R'R'
R''
HCOOH
R
X
H
N
X=CH,N,S
R'N
H
R
OH
COOMe(NO2\CN\CF3)
J. Am. Chem. Soc. 2009, 131, 10806
Angew. Chem. Int. Ed. 2009, 48, 6097
J. Am. Chem. Soc. 2009, 131, 7520
J. Am. Chem. Soc. 2009, 131, 5072Tetrahedron
2009, 65, 3085
J. Am. Chem. Soc. 2010, 132 12203
Angew. Chem. Int. Ed. 2010, 49, 6169
Org. Lett. 2010, 12, 3140
Org. Lett. 2010, 12, 2511
J. Am. Chem. Soc. 2010, 132, 5916
J. Am. Chem. Soc. 2010, 132, 3648
J. Am. Chem. Soc. 2010, 132, 686
Angew. Chem. Int. Ed. 2010, 49, 1275
R1
R2
COOH
Ha
Hb
position selective C-H functionlization
Science 2010, 327, 315
mutually repulsive 2,6-dialkylpyridineligand
J. Am. Chem. Soc. 2008, 130, 14082-14083
COONa/K
H
Science, 2009, 323, 1593
Yuzo Fujiwara, Science 2000,287, 1992
2.Activation of sp3 C-H Bonds
H
R'
O
NHR''
OMe
H
R'
COOK
R''
ON
t-BuO
RH
NR'
R''H
H H
N
ON
O
R''R'
MeR
H
R
H
O
NH
Ar
J. Am. Chem. Soc. 2010, 132, 17378
J. Am. Chem. Soc. 2010, 132, 3680
J. Am. Chem. Soc. 2007, 129, 3510Org. Lett. 2006, 8, 3387
Org. Lett. 2006, 8, 5685
J. Am. Chem. Soc. 2006, 128, 12634
J. Am. Chem. Soc., 2008, 130, 7190
HH
O
NH
C6F5
J. Am. Chem. Soc. 2009, 131, 9886
Angew. Chem. Int. Ed. 2005, 44, 7420Angew. Chem. Int. Ed. 2005, 44, 2122
J. Am. Chem. Soc. 2008, 130, 14082–14083A new carboxylation reaction of broadly useful aryl andvinyl carboxylic acids using a C-H activation/CO insertion sequence.
R
COOH
HR
COOH
COOH
10 mol % Pd(OAc)2,
2 eqNaOAc, 2 equiv Ag2CO3,1 atm CO
RH
COOH
R'R'
RCOOH
COOH
R'R'
R
R'R'
O
O
O
23 examples up to 95% yield
H
Ph
COOHHOOC
Ph
COOH
very useful in the synthesis of natural productscontaining a succinic acid/anhydride moiety
Privous method: the ortho-lithiation/CO2 insertion process directed by amide groups
Pd(II)-Catalyzed Carboxylation of Aryl and Vinyl C-H Bond
O
N(i-Pr)2
1.sBuLi,TMEDA2.CO2
NMe2
1.nBuLi,TMEDA2.CO2
O
N(i-Pr)2
COOLi
NMe2
COOLi
X-ray crystallography of the first C-H insertion intermediate isolated from the cyclometalation of carboxylic acids.
Angew. Chem. Int. Ed. 2009, 48, 6097 –6100
Challenge: Pd(II)-catalyzed intermolecular alkylation of C-H bonds with alkyl halides
S. J. Tremont, H. U. Rahman,J. Am. Chem. Soc. 1984, 106,5759
NHAc
H
a large excess of AgOAc is required to scavenge theiodide from Pd-I species in this case
NHAc
"Ortho-alkylation of acetanilides using alkyl halides and palladium acetate"
MeI
Pd(OAc),AgOAc目前 C-H 活化多为形成 C(sp2)-C(sp2) 的反应，烷基化反应相对较少
COOH
ClCl
O
O
O
O
Cl
O
O
2
SN2 side productUsing K2HPO4 as base,no SN2 side product
Although the oxidation of the arylpalladium(II) intermediate by MeI to Pd(IV) was previously proposed (intermediate 8), in light of previous discoveries that arylpalladium species react with electrophiles such as aldehydes and ketones,direct s-bond metathesis between the aryl–Pd bond and the alkyl halide cannot be ruled out (intermediate 9)
not a Friedel–Crafts-typereaction
Science,2010,327,315-319Angew. Chem. Int. Ed. 2010, 49, 6169–6173
R1
R2
COOH
Ha
Hb
position selective C-H olefination
Pd-catalyzed arene C–H olefination
Challenge:1. the substrates that are typically effective in palladium-catalyzed C–H activation are synthetically restrictive, either because they are limited to electron-rich arenes or heterocycles, or because they possess impractical chelating functional groups to promote metalation. These directing groups include those thatare irremovable and recalcitrant to undergo further synthetic elaboration, such as Py, and those that are removable but require several steps for installation and detachment, such as oxazoline. 2. methods for effecting position-selective C–H activation on multiply substituted arenes , particularly via ligand control, remain underdeveloped
COOH
R'R''
HR'''R
5mol%Pd(OAc)25mol%BQ2eq KHCO31atm O2,1 eq t-AmylOH
COOH
R'R''
R'''
R
24 examples
No traditional Mizoroki-Heck reaction product
J. Am. Chem. Soc. 2009, 131, 5072–5074
Meta-olefination of highly electron-deficient arene
Fujiwara-type reactions using electrondeficient arenes using electrondeficientarenes under various reported conditions have two problems ：1.electron-deficient arenes were unreactive due to their poor coordination with Pd(O
Ac)22.reoxidation of Pd(0) by O2 was not possible in the absence of electron-rich arenes,
external ligands, or co-oxidants
Py: the most efficient ligands to promote the reoxidation of Pd(0) by oxygen
Yu hypothesized that, in these systems,displacement of the pyridyl ligand by the electron-deficient arene substrate is energetically disfavored due to the strength of the Pd-N bond.Even upon prior loss of acetate and formation of the correspondingPy2Pd(OAc)+, the resulting complex remained insufficientlyelectrophilic for C-H activation to take place
increase in steric bulk at the 2 and 6 positions of the pyridine ring to weak Pd-N bond strength
the bond length of Pd-N is 0.05 Å longer than that of (Pyridine)2Pd(OAc)2
Py2Pd(OAc)2 complexes are highly stable under the same conditions
This paper was featured in:Perspectives in Science: Copper Puts Arenes in a Hard PositionRSC Chemistry World: Copper catalysts give meta aromaticsResearch Highlights in Nature Chemistry: Electrophilic arylation: Substitution successChemical and Engineering News: Dodging The Substitution LawsScience News: Helping Molecules Reach MetaAngewandte Chemie: Meta-Selective Transition-Metal Catalyzed Arene C-H Bond FunctionalizationThis paper was voted as one of the top 12 papers of 2009 by Chemical and Engineering News Chemical Year in Review 2009
Science, 2009, 323, 1593
How to access the isomer that is not anticipated by these rules?Solutions to this problem often require numerous FG additions or manipulations in order to tailor the directing electronic properties of the precursor to furnish the desired product
吲哚能发生亲电取代反应，多取代于 3 号位
J. Am. Chem. Soc. 130, 8172
Sanford, J. Am. Chem. Soc. 128, 4972
We cannot rule out coordination of the Cu(III) species at the ortho position, followed by a migration to the meta site and arylation. However, we do not see any sign of ortho-arylation that may be expected through this pathway
Although we cannot be certain of the precise mechanism of the reaction at this stage, a possible rationalization could involve the highly electrophilicCu(III)-aryl species activating the aromatic ring sufficiently to permit an anti–oxy-cupration of the carbonyl group of an acetamide across the2,3 positions on the arene ring
Christina White (UIUC)
Melanie Sanford (UMichigan)
R
H
Allylic C-H Oxidation
Alliphatic C-H Oxidation
H
S SO O
Ph PhPd(OAc)2
• +BQ
L
C H
cat [Pd]
NO O
X
N+R
F
or
Keith Fagnou(U Ottwa)Passed away in Nov. 2009
Matthew Gaunt (Cambridge)
Yuzo Fujiwara (Kyushu University)
Masahiro Miura (Osaka Univ.)