Miyaura, N. Cross-Coupling Reactions: A Practical Guide. Springer: 2002. Steven, V. L.; Thomas, A. W. Angew. Chem. Int. Ed. 2003, 42, 5400.
5
The general catalytic cycle
The Evolution of Cross-Coupling Reactions
偶联反应
2010年诺贝尔化学奖
2
偶联反应的用途
3
Comments
• …until the discovery and development of cross-coupling reactions starting in the 1970s, there were no simple, general direct methodologies known for C-C formation between unsaturated species … --- Peter J. Stang • …total synthesis has benefited enormously from the palladium-catalyzed crosscoupling reactions… --- K. C. Nicolaou • … somebodies in this field would win the
OPSS Lectures:
Preactivation [M]
R R' R X
Reductive Elimination [M]
R R'
Oxidative Addition [M]
R X
m
X
m R'
Transmetalation
[M] = Fe, Co, Ni, Cu, Pd, Ru, Rh ... ... m = Li, Mg, B, Si, Sn, Zn, Zr, Al ... ...
6
Contents
• Introduction • The evolution of cross-coupling reactions
• The contributions from China
• Summary and outlook
7
The evolution of cross coupling reactions
FR2 M KF, n-BuF, NaOH ... M= SiR(3-n)Xn ; X=Cl, F; Hiyama Si(OR)3 Tamao-Ito
16
Kumada-Corriu-Tamao Reaction
Makoto Kumada
Robert J. P. Corriu
Tamao, K.; Kumada, M. et al. J. Am. Chem. Soc. 1972, 94, 4374 Corriu, J. P.; Masse, J. P. Chem. Commun. 1972, 144 Murahashi, Shun- Ichi. et al. J. Organomet. Chem. 1975, 91, C39 Tamao, K. J. Organomet. Chem. 2002, 653, 23
Transmetalation
R M R ZnX M= Cu, Li, Mg, B, Cd, Hg ... ... ZnX2
FG = CO2R, enoate, CN, enone, halide, (RCO)2N, (TMS)2Si, RNH, NH2, RCONH, (RO)3Si, (RO)2P(O), RS, RS(O), RSO2, PhCOS ... ...
FG= Br, CONR2, CN, CO2Et ...
Paul Knochel
Knochel, P. et al. Angew. Chem. Int. Ed. 2000, 39, 4414 Knochel, P. et al. Angew. Chem. Int. Ed. 2003, 42, 4302
• The organometallic reagents • The organic electrophiles • The catalysts
[M]
R R'
[M]
R X
• Use of new technologies
X-m
R-m
What can be translated to the transition metal complex?
Heck Reaction
11
The mechanism of Heck Reaction
12
The mechanism of Heck Reaction
13
The mechanism of Heck Reaction
14
The mechanism of Heck Reaction
15
Application
R X + R' m
catalyst [M]
R R'
X= I, Br, Cl, OTf, F, CN, OTs, OMs ... ... [M]= Fe, Co, Ni, Cu, Pd, Ru, Rh ... ...
m= Li (Murahashi) Mg (Kumada-tamao, Corriu) B (Suzuki-Miyaura) Si (Tamao-Kumada, Hiyama-Hatanaka) Sn (Migita-Kosugi, Stille) Zn, Zr (Negishi) Al (Nozaki-Oshima, Negishi) Cu (Normant) ... ...
The true breakthrough
9
Introduction of organometallic reagents
1972 Mg 75 77 79 81 Li Sn B Cu 95 Ge 97 Mn
M=
1970 75 80 85 90 95 2000
76 Al, Zn, Zr
88 Si, Pb, Bi, Sb
+ L
I CuI
CuILn + R Pd L Cu R
Sn X
NR2 NR2
R3SnCl
R3SnF
Fluoride anion Copper Effects Fouquet, E.; Pereyre,; M. Rodriguez, A. L. J. Org. Chem. 1997, 62, 5242
Knochel, P. et al. Tetrahedron Lett. 2001, 42, 5717
Martin, R.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 3844
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Negishi Reaction
Ei-ichi Negishi
• Good functional group compatibility • Mild conditions • Facility in preparation • Water sensitive • Zn waste
• Easily available • Mild conditions • Excellent reactivity
Kohei Tamao
• Moisture sensitivity • Poor tolerance
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Functionalized Organomagnesium
I FG MgX iPrMgBr / THF -40℃ -25℃ FG
• • • •
Neutral conditions Excellent compatibility Sn: toxicity, waste High cost “Radical” Twist Vs “Radical” Recovery
Kosugi, M.; Migita, T. J. Organomet. Chem. 1973, 56, C11 Kosugi, M.; Migita, T. et al. Chem. Lett. 1977, 1423 Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636
99 In
2000 Hg
The confliction: reactivity and selectivity
Mg 1.2 Zn 1.6 Sn 1.8 Si 1.8 B 2.0
increasing reactivity, decreasing selectivity
Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359
Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93, 2117
Boudier, A.; Flachsmann, F.; Knochel, P. Synlett 1998, 1438
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Kosugi-Migita-Stille Reaction
John K. Stille
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Preparation of organozinc
Insertion of Zinc
R X
+
Zn
THF, 5-45℃
R
Zn
> 85%
X = I, Br ; R =alkyl, aryl, benzyl, ally
Iodine-Zinc Exchange
R I cat CuI Et2Zn R2Zn