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1. 有機金属化学の基礎 2. パラジウムの化学 Allyl Palladium の反応

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1. 有機金属化学の基礎
2. パラジウムの化学
- Allyl Palladium の反応
Mizoroki-Heck反応
Migita-Kosugi-Stille カップリング反応
Miyaura-Suzuki カップリング反応
(Tamao-Kumada-Corriu カップリング反応)
3. カルベンの化学
Schrock carbene
Fischer carbene
Grubbs catalyst RCM (閉環メタセシス)
4. 不斉合成
光学活性化合物の入手方法
不斉還元
不斉酸化
不斉アルキル化
不斉1,4付加
1
酸化と還元、元素の酸化数および原子価
元素の酸化数:ある元素が関与する結合中の電子対を電気陰性度の大きい元素に
割り当てたとき、その元素の原子上に残る電荷の数
_
Ph3P
CH3
Ph3P
Pt
Ph3P
CH3
Pt2+
Ph3P
CH3
_
CH3
アニオン
中性分子
白金の酸化数は+2
Pt2+, PtII, Pt(II)
実際の酸化数と違うので、形式酸化数と呼ぶ
formal oxidation number
2
酸化的付加と還元的脱離
oxidative addition and reductive elimination
_
A
M
+
M2+
M
B
A
A
酸化的付加
還元的脱離
_
B
B
_
H
M
+
M2+
M
H
還元的脱離
H
H
酸化的付加
H
_
H
3
配位子のハプト数
hapticity
M
M
M
M
3-ally
1-ally
H2C
CH2
HC
H
CH
M
M
M
2-alkene
2-alkyne
4-diene
M
M
5-cyclopentadienyl
6-benzene
H
M
2-hydrogen
4
形式酸化数、d電子数、総電子数
Ph3P
CH3
白金の形式酸化数: 2 Pt(II)
Pt
Ph3P
CH3
金属のd電子数:
d8
総電子数:
16e
_
2 (CH3)
d8
= 8e
2x2e
= 4e
2 PPh3
2x2e
= 4e
Pt(II)
_
Ph3P
Ph3P
中性分子
Pt2+
CH3
_
16e
CH3
アニオン
5
配位子のハプト数、形式電荷、供与電子数
ハプト数
形式電荷
供与電子数
M R
alkyl
1
-1
2
M H
hydride
1
-1
2
M X
halide
1
-1
2
M OR
alkoxide
1
-1
2
acyl
1
-1
2
1-alkynyl
1
-1
2
1-allyl-allyl)
1
-1
2
acetylide
1
-1
2
O
M
M
C
C
R
C
M
M
R
6
配位子のハプト数、形式電荷、供与電子数
ハプト数
形式電荷
供与電子数
R
M C
carbene (Fischer)
1
0
2
carbene (Schrock)
1
-2
4
M C R
carbyne
1
-3
6
M CO
carbonyl
1
0
2
2-alkene
2
0
2
2-alkyne
2
0
2
R'
R
M C
R'
C
M
C
C
M
C
7
配位子のハプト数、形式電荷、供与電子数
ハプト数
形式電荷
供与電子数
M
3-allyl
3
-1
4
M
4-diene
4
0
4
5-cyclopentadienyl
5
-1
6
6
0
6
M
5
 -Cp
6-arene
M
8
配位子のハプト数、形式電荷、供与電子数
M
M
M
H
X
R
O
ハプト数
形式電荷
供与電子数
M
-hydride
1
-1
2
M
-halide
1
-1
4
-alkoxide
1
-1
4
-carbonyl
1
0
2
-alkylidene
1
-2
4
3-carbonyl
1
0
2
3-alkylidyne
1
-3
6
M
O
M
M
C
R2
C
M
M
O
M
C
M
M
M
R
C
M
M
9
ハプト数
M
X
X
M
M
M H
H
M
M
供与電子数
halide
1
-1
2
-halide
1
-1
4
hydride
1
-1
2
-hydride
1
-1
2
X
M
形式電荷
X
M
M
M
10
金属の形式酸化数、d電子、錯体の電子数
Ni(PPh3)2(CH3)Cl
ニッケル10族元素
2 x PPh3
d8
2 x 2e
8e
= 4e
CH3
1 x 2e
= 2e
Cl
1 x 2e
= 2e
Ni(II)
ニッケルの形式酸化数2
Ni(II), d8, 16e
16e
OC Fe
OC
_
鉄8族元素
2 x CO
d8
2 x 2e
8e
= 4e
Cp
1 x 6e
= 6e
Fe(0)
18e
鉄の形式酸化数0
Fe(0), d8, 18e
11
18電子則、有効原子番号則
18-electron rule, effective atomic number rule
N
CO
N
Cr
Co
Ph3P
PPh3
H PPh3
Ni
OC
CO
CO
RuH2(PPh3)4
[Co(H2O)6]2+
V(CO)6
RuCl2(PPh3)3
12
Quiz 1.
_
Ph3P
Ir
Ph3P
CO
イリジウム9族元素
I
Rh
OC
I
CO
CH3
イリジウム9族元素
2-
I
I
Ir+
Ti
CH2
CO
ロジウム9族元素
チタン4族元素
13
O
H2C CH2CH3
H
CH2CH2CH3
O
H
C
L2Rh
HRh(CO)L2
H
d8, 16e
L2Rh
CH2CH2CH3
H
CO
CHCH3
CO
CH2
d8, 18e
d6, 18e
Hydroformylation
H2
CH2CH2CH3
O
C
L2Rh
L2Rh
CO
CH2CH2CH3
CO
8
d , 16e
d8, 16e
CO
L2Rh
CO
CH2CH2CH3
CO
d8, 18e
14
酸化的付加
oxidative addition
A
酸化的付加
LnM
A
+
B
L nM
還元的脱離
B
低原子価
配位不飽和
H
Ph3P
Cl
Ir
CO
PPh3
Ph3P
+
H
H
cis-addition
Cl
Ir
H
PPh3
CO
Vaska complex
Ir(III), d6, 18e
Ir(I), d8, 16e
+
H3C
I
trans-addition
CH3
Ph3P
CO
Ir
Cl
PPh3
I
Ir(III), d6, 18e
15
水素の酸化的付加
L
L
Pt
+
H
L
L
H
Pt
Pt
H
L
キ
H
H
H
L
Pt(II), d8, 16e
10
Pt(0), d , 14e
L
H
Pt
Pt
H
L
LUMO
L
L
H
L
H

H
Pt
Pt
H
L
HOMO
H
L
L
H

16
ハロゲン化アルキルの酸化的付加
-
+
LnM
SN2
LnM
+
R
キ
X
LnM
R
+
_
X
R
X
R
キ
R
L nM
LnM
X
X
三中心遷移状態
Ph3P
D
H
C
Pd
Ph3P
Br
Ph
Pd(0), d10, 14e
Pd(II), d8, 14e
(PCy3)2Pd
Pd(0), d10, 16e
H D
Ph3P
Pd C
Ph
Ph3P
X
HR
+
_
Br
Ph3P H
D
Br Pd C
Ph
Ph3P
Pd(II), d8, 16e
J. K. Stille, J. Am. Chem. Soc., 98, 5832 (1976).
R
R
(PCy3)2Pd+
XPd H
X
Cy3P
H
Pd(II), d8, 16e
17
ハロゲン化アルキルの酸化的付加
S N2
LnM
LnM
R
X
キ
LnM
R
+
_
X
R
+
X
R
キ
R
LnM
LnM
X
X
三中心遷移状態
Pd
キ
Ph3P
Ph3P
+
X
Pd +
X
Ph3P
Ph3P
_
Pd(0), d10, 14e
Ph3P
X
X
Pd
Pd
Ph3P
Pd(II), d8, 16e
PPh3
Ph3P
X: I > Br >> Cl
18
PhEt2P
CH3
CH3
Pd +
Pd
PhEt2P
キ
PhEt2P
PhEt2P
_
Pd(II), d8, 16e
Ph3P
Pd
+
H3C
Ph3P
Pd(0), d10, 14e
19
還元的脱離
reductive elimination
A
酸化的付加
LnM
+
A
B
L nM
還元的脱離
L
R
解離経路
M
B
R
R'
+
ML
R
R'
+
ML2
R
R'
+
ML3
R'
-L
+L
L
R
直接経路
M
L
R'
-L
+L
L
L
R
M
L
R'
会合経路
20
CO挿入
CO insertion ?
alkyl migration ?
O
CO
L nM
LnM
R
キ
O
C
L nM
R
C
R
Rの立体化学は保持
RとCOはシス
CH3
OC
OC
Mn
CO
OC
CO
OC
Mn
COCH3
CO
L
L
OC
OC
Mn
COCH3
CO
CO
CO
CO
Mn(I), d6, 18e
Mn(I), d6, 16e
Mn(I), d6, 18e
21
CO挿入
CO insertion
CH3
OC
- CO
CH3
OC
OC
OC
Mn
OC
CO
OC
Mn
CO
CO
CO
CO
CO
Mn
CH3
CO
25%
CO
CO
CH3
CO
CH3
CO
- CO
OC
Mn
CO
CO
CO
OC
OC
Mn
CO
cis
CO
CO
75%
22
CO挿入
CH3 migration
CH3
OC
- CO
OC
CO
CO
OC
Mn
CO
OC
Mn
CH3
CO
CO
CO
25%
OC
OC
CH3
CH3
CO
CO
Mn
CO
CO
- CO
OC
CO
Mn
CO
CO
H3C
CO
OC
Mn
CO
CO
cis
CO
CO
50%
CH3
OC
- CO
CO
CO
Mn
CO
CO
OC
CO
H3C
Mn
CO
trans
CO
CO
25%
23
CO
Ph3P
Cl
Rh
K
R
PPh3
ROC
Ph3P
Cl
Rh
Cl
PPh3
Cl
R
K
C2H5, C6H5CH2
> 50
C6H5CH2CH2
17
CH3
3.4+0.2
-
p-ClC6H4CH2
0.07
C6H5
< 0.05
ClCH2, H
<0.02
24
アルケン、アルキン挿入反応、  脱離反応
B
A
C
LnM
A C
L nM
C
D
挿入反応
B
A
脱離反応
L nM
R
挿入反応
A
B
脱離反応
LnM
R
C
R
D
C
C B
R
PMe3
Co
Co
CD3
CD3
Co
CD3
CD3
CD3
H
- CD3H
CD3
Co
PMe3
D3C
25
トランス影響、トランス効果
trans influence, trans effect
配位子置換反応
解離機構(配位飽和18電子錯体)
HCo(CO)4
8
- CO
+ CO
Co(I), d , 18e
HCo(CO)3
X
Co(I), d8, 18e
d8 平面正方形16電子錯体
Y
L
M
HCo(CH2=CH2)(CO)3
Co(I), d8, 16e
会合機構(配位不飽和16電子錯体)
T
H2C CH2
Y
L
L
L
T
M
L
-X
X
T
M
L
Y
立体保持
トランス効果の序列
CO, CN-, CH2=CH2 > PR3, H- > CH3- > C6H5-, I- > Br-, Cl- > NH3, H2O
26
トランス効果の序列
CO, CN-, CH2=CH2 > PR3, H- > CH3- > C6H5-, I- > Br-, Cl- > NH3, H2O
置換反応に及ぼす配位子Tの動的効果
トランス影響の序列
H-, CH3-, C6H5- > PR3, CN- > CO, CH2=CH2 > I-, Br- > Cl- > NH3, H2O
配位子TによってM-X結合がどの程度弱められているかを示す静的効果
M-X結合距離のX線構造解析
M-X結合のIR伸縮振動
M-X結合のNMR結合定数
27
 供与と 逆供与
Dewar-Chatt-Duncanson モデル
C
M
C
M
C
C
 (d
M
)  供与
C
 (d
 供与の寄与大
C
)  逆供与
C
M
 供与の寄与大
C
IR 伸縮振動波数
C=C 50-60 cm-1 低波数シフト
C=C 150-160 cm-1 低波数シフト
28
 供与と 逆供与
O
M
n  供与
dM
M
dM
_
M C
C
+
O
_ +
M C
O
C
O
  逆供与
M C
O
IR 伸縮振動波数
CO 2143 cm-1
末端カルボニル 2125-1850 cm-1
29
ホスフィン配位子
酸性度定数 (pKa)
11.40
P(t-Bu)3
P(c-C6H11)3
9.65
PEt3
PMe3
8.69
8.65
PMePh2
4.59
PPh3
2.73
 受容性
NO > CO > RNC > PF3 > PCl3 > P(OR)3 > PR3 > RCN > RNH2 > NH3
X
M
P
X
d
X
 相互作用
30
ホスフィン配位子
立体因子
円錐角  (cone angle)
P
P
2/2
3/2 M 1/2
 M
3
 = (1/3)i
i=1
P(o-MeC6H4)3
194
PBu3
136
P(t-Bu)3
182
P(c-C6H11)3
PPh3
179
145
PEt3
PMe3
132
118
P(OEt)3
107
31
ホスフィン配位子
立体因子
配位挟角  (bite angle)
P

Ph2
P
Rh(cod)+ ClO4P
Ph2
83.8
PPh2
Rh(ndb)+ ClO4PPh2
91.8
P
M
O
PPh2
Rh(nbd)+ ClO4-
O
98
PPh2
32
-Allyl Palladium Chemistry
X
Nu
+
Pd(0)Ln
PdL2+
_
_
_
Nu + Pd(0)L + X
n
X
X = OAc (most common), OCO2R, OP(O)(OR)2, OPh, OH, halide, SO2Ph, NO2, NR2,
O
NR3X, PPh3X,
O
COOEt
EtOOC
O
_
Nu = malonate, O,N,S nucleophiles, R-M (M = Mg, Zn, B, Al, Sn, Si)
catalyst = Pd(0)
33
Catalytic Cycle
PdL4
18e
- 2L
Nu
X
PdL2
14e
PdL2
16e
PdL2
Nu
16e
_
Nu
PdL2+
16e
X
_
X
34
R
R
R
_
ligand attack
Nu
Nu
Nu
PdL2+
X
LnPd
_
_
Nu
metal attack
R
R
R
reductive elimination
Nu
PdL2
Nu
Nu
LnPd
ligand attack; soft carbanions suh as malonate, enolates, amines
metal attack: RSnBu3, RZnX, Cp2Zr(R)Cl, RAlMe2, RMgX, RLi, NaBH4
35
Stereochemistry
CO2Me
CO2Me
Pd(PPh3)4
_
+
CO2Me
CH(CO2Me)2
THF
CO2Me
OAc
CO2Me
PdL2+ OAc
_
retention
CO2Me
CO2Me
_
+
CO2Me
Pd(PPh3)4
CH(CO2Me)2
THF
CO2Me
OAc
CO2Me
PdL2+ OAc
retention
36
_
Stereochemistry
CO2Me
CO2Me
CO2Me
Pd2(dba)3
+
Cl
benzene
THF
acetone
DMF
DMSO
CO2Me
PdCl
PdCl
retention
inversion
100 : 0
95 : 5
75 : 25
29 : 71
3 : 97
CO2Me
Pd(PPh3)4
benzene
Cl
PdCl
inversion
H. Kurosawa, J. Am. Chem. Soc., 114, 8417 (1992).37
NuH
Pd-Catalyzed Reactions Involving -Allyl Palladium
C, O, N nucleophiles
Nu
R
M'R'
transmetallation
R
M'Ar
X
Pd (0)
transmetallation
R
R'
Pd
R
R'
R
X
Ar
R
M'
X
transmetallation
R'
R
CO, ROH
carbonylation
CO2R
R
R'M'M'R'
metallation
H
M'R'
R
_
R
hydrogenolysis
R
-elimination
R
38
Asymmetric Alkylation
Review: B. M. Trost, Chem. Rev., 96, 395 (1996)
CO2Me
CO2Me
SO2Ph
+
NaCH
CO2CH3
OAc
Pd(PPh3)4 / L*
refluxing DME
H
(+)-cis
_
O
CO2CH3
PPh2
L* =
PhO2S
optical yield 46%
PPh2
O
H
(+) DIOP
CO2Me
_
Nu
Pd +
*L
L*
B. M. Trost, J. Am. Chem. Soc., 99, 1649 (1977)
39
Ph
Ph
+
OAc Ph
NaCH(CO2CH3)2
[-C3H5PdCl]2 / L*
THF, 25 °C
Ph
(CH3O2C)2HC
Ph
Ph
optical yield 84%
L* =
Ph2P
PPh2
S,S-Chiraphos
Ph
Ph
+
OAc
NaCH(CO2CH3)2
[-C3H5PdCl]2 / L*
THF, 25 °C
Ph
Ph
(CH3O2C)2HC
optical yield 22%
B. Bosnich, J. Am. Chem. Soc., 107, 2033 (1985)
B. Bosnich, J. Am. Chem. Soc., 107, 2046 (1985)
40
OAc
OAc
 interconversion
Pd(0)
Pd(0)
fast
Pd
P
P
*
major
P
*
Pd
Pd
Pd
P
P
*
P
P
P
*
minor
_
_
Nu
fast
fast
slow
Nu
major
Nu
slow
Nu
minor
41
Ph
Ph
+
OAc
NaCH(CO2CH3)2
[-C3H5PdCl]2 / L*
Ph
THF, 40 °C
Ph
CH(CO2CH3)2
90% ee
OH
Ph
Ph
H
R
P
Me
NuPd
Fe
CH
C
O H
CR
P N
H2
H
Ph Ph
Me
1a: X = NMe
OH
X
L* =
OH
Fe PPh2
PPh2
1b: X = N
OH
(R)-(S)-BPPF-X
1c: X = MeN
OH
T. Hayashi, Tetrahedron Lett., 27, 191 (1986)
42
Ph
Ph
+
OAc
CH2(CO2CH3)2
[-C3H5PdCl]2 / L* Ph
CH2Cl2, rt
CH(CO2CH3)2
KOAc / BSA
L* =
Ph
98% ee
G. Helmchen, Tetrahedron Lett., 34, 1769 (1993)
A. Pfaltz, Angew. Chem., 32, 566 (1993)
J. M. J. Williams, Tetrahedron Lett., 34, 3149 (1993)
O
PPh2 N
Pri
Me
Me
H
O
N
Ph
P
Pd
Ph
or
Me
Me
H
O
N
Ph
Nu-
Pd
P
Ph
Nu-
43
Chiral Pocket
Review: B. M. Trost, J. Org. Chem. 69, 5813 (2004)
B. M. Trost, Aldchimica Acta, 40, 59 (2007)
R
R
+
OAc
R
[-C3H5PdCl]2 / L*
CH2(CO2CH3)2
CH2Cl2
Cs2CO3
R
CH(CO2CH3)2
O
O
NH HN
L* =
PPh2Ph2P
When R = Ph, 9% yield along with 79% recovery of the starting material
When R = Me, 98% with 92% ee
B. M. Trost, J. Am. Chem. Soc., 118, 6520 (1996)
44
O
O
O
Pd2(dba)3.CHCl3 / L*
O
THF, 0 °C
N
O
NHTs
TsHN
O
Ts
88% ee
PPh2
O
O
O
O
NHTs
TsHN
L*
H
N
L* =
O
Ph2P
H
N
O
Pd
L*
B. M. Trost, Angew. Chem., Int. Ed. Engl., 31, 228 (1992)
45
脱離
O
O
O
NHTs
TsHN
L*
O
O
O
L*
Pd
O
+
Pd
L*
NHTs
O
Pd
N
Ts
L*
L*
攻撃
L*
O
O
N
脱離
O
O
Ts
O
NHTs
TsHN
L*
Pd
L*
O
O
O
O
O
Pd L*
TsHN
攻撃
N
Pd L*
Ts
L*
L*
O
O
N
Ts
46
O
O
CO2CH2Ph
CO2CH2Ph
OAc
+
[-C3H5PdCl]2 / L*
toluene, 0 °C
teramethylguanidine
86% ee
O
L* =
O
NH HN
PPh2Ph2P
O
O
CO2CH2Ph
+
OCO2CH3
[-C3H5PdCl]2 / L*
toluene, 0 °C
teramethylguanidine
CO2CH2Ph
H
88% dr
97% ee
B. M. Trost, J. Am. Chem. Soc., 119, 7879 (1997)
47
O
O
+
OAc
[-C3H5PdCl]2 / L*
LDA/Me3SnCl
DME. rt
99% (88% ee)
O
L* =
O
NH HN
PPh2 Ph2P
B. M. Trost, J. Am. Chem. Soc., 121, 6759 (1999)
nitoroalkane
B. M. Trost, J. Am. Chem. Soc., 122, 6291 (2000)
48
O
O
O
O
O
L* =
Pd2(dba)3CHCl3/L*
PPh2 N
THF, 25 °C, 2 h
But
85% (87% ee)
B. M. Stoltz, J. Am. Chem. Soc. 126, 15044 (2004)
O
O
O
O
Pd2(dba)3CHCl3/L*
toluene, 23 °C, 20 h
L* =
PPh2
H
N
O
Ph2P
H
N
78% (78% ee)
O
B. M. Trost, J. Am. Chem. Soc., 127, 2846 (2005)
B. M. Trost, J. Am. Chem. Soc., 131, 18343 (2009)
49
O
O
O
Pd(OAc)2/L*/HCOOH
O
dioxane, 40 °C, 10 h
88% (94% ee)
O
L* =
PPh2 N
O
_
O
But
O
_
O
Pd+
Pd+
-CO2
B. M. Stoltz, J. Am. Chem. Soc., 128, 11348 (2006)
50
OBoc
[-C3H5PdCl]2 / L*
LiHMDS, BF3.OEt2
+
dioxane, 25 °C
N
86% (95%ee)
unstabilized nucleophile
L* =
N
O
O
NH HN
PPh2 Ph2P
B. M. Trost, J. Am. Chem. Soc., 130, 14092 (2008)
51
Asymmetric Inducion with Mono-substituted Allyl Systems
R
R
Dynamic Kinetic Asymmetric
Transformation
+
X
X
M(0)
R
X
M(0)
+
R
M
B
Nu-
L*
ent-A
A
+
R
M(0)
+
R
M
M
enantiodiscrimination step
L*
Nu-
R
R
Nu
Nu
Review: B.M. Trost, Aldrichimica Acta, 40, 59 (2007)
52
OH
O
O
+
[-C3H5PdCl]2 / L*
HN
O
N
O
CH2Cl2, rt
99% (75:1)
O
98%ee
O
L* =
O
NH HN
PPh2Ph2P
Nu
H
_
O
Pd+
B. M. Trost, J. Am. Chem. Soc., 122, 5968 (2000)
53
[(C3H5)PdCl]2 / L*
OAc
+
Ph
Ph
CH2(COOMe)2
Ph2P
R
CH2Cl2, 0 oC
O
Me
S
i
L* =
CH(COOMe)2
BSA, KOAc
Pr
Ph
Ph2P
Ph
O
Me
S
Pri
L* =
R
R
Ph
42
70
4-MeOC6H4
44
58
2,3,5,6-F4C6H
18
22
4-tBuC6H4
3,5-Me2C6H3
3,5-tBu2C6H3
1-Nap
2-Nap
Bn
Cy
70
63
33
60
56
89
91
77
85
51
74
76
75
81
t
Bu
98
91
D. A. Evans, J. Am. Chem. Soc., 122, 7905 (2000)
54
[(C3H5)PdCl]2 / L*
OAc
CH2(COOMe)2
+
Ph
Ph
Ph2P
O
BSA, KOAc
CH2Cl2, -20 oC
R'
L* =
R'
S
CH(COOMe)2
Ph
Ph2P
i
Ph
O
R'
S
Pri
L* =
Pr
But
But
Me
91
98
Ph
75
91
i
75
69
Pr
Ph2P
O
L* =
S
But
R1
R2
Pri
R1
R2
H
Me
H
Me
H
H
Me
Me
67%ee
91%ee
98%ee
85%ee
55
Me
+
SbF6-
Me
O
Me
Ph P
S
But
Ph
Pd
H
H
Ph
Me
2.3 : 1
Me
O
Me
Ph P
S
But
Ph
Pd
Ph
Ph
Ph
H
H
Nu-
Nufast
slow
Me
Me
Me
O
Me
Nu
Ph P
S
H
Ph
Pd
Ph
H
t
Bu
Ph
+
SbF6-
H
Me
O
Me
Ph P
S
t
Ph
Ph Pd H Bu
Ph
H
Nu H
56
[-C3H5PdCl]2 / L*
Li2CO3
OCOOMe
+ CH2(COOEt)2
CH(COOEt)2
H2O, 40 oC, 12 h
O
94% yield
98%ee
H
O
PS
O
O
n
HN C
(CH2)3
N
N
M
PPh2
recyclable amphiphilic resin-supported catalyst
M = PdCl(3-C3H5)
recyclable by filtration
1st run
2nd run
3rd run
60% 91%ee
70% 90%ee
65% 90%ee
OCOOMe
at 25 oC
Y. Uozumi, J. Am. Chem.Soc., 123, 2919 (2001)
57
Ruthenium-Catalyzed Reaction
CO2Me
_
+
CH(CO2CH3)2
OC(O)OMe
decane, 60 oC
CO2Me
立体反転
+
CO2Me
CpRu(cod)Cl
NH4PF6
CH(CO2CH3)2
99% (trans/cis = 97/3)
立体反転
Ru(cod)Cp
T. Mitsudo, Organometallics, 18, 4742 (1999)
58
Ruthenium-Catalyzed Reaction
O
t
Bu
O
Me
Ru
Ph
AN
AN
Ph
+
OAc
NaCH(CO2CH3)2
P
Ar2
THF, 20 °C
Ph
Ph
CH(CO2CH3)2
98% (97%ee)
S. Takahashi, J. Am. Chem. Soc., 123, 10405 (2001)
59
Rhodium-Catalyzed Reaction
OCO2Me
+ NaCH(CO2Me)2
Me S
RhCl(PPh3)3
P(OMe)3
CH(CO2Me)2
Me S
30 oC
95%ee
97%ee
Me
Me
OCO2Me
+
CH(CO2Me)2
Me
CH(CO2Me)2
99% (42 : 1)
Me
83% (2 : 1)
OCO2Me
D
CH(CO2Me)2
OCO2Me
+
Me
D
Me
Me
D
Me
Me
CH(CO2Me)2
Me
92% (>19 : 1)
P. A. Evans, J. Am. Chem. Soc., 120, 5581 (1998)
60
Iridium-Catalyzed Reaction
[IrCl(cod)]2
Ph
O
P N
O
OPh
Ph
Ph
OCO2Me
+
Ph
PhOLi
THF, 50 oC, 20 h
86% (96%ee)
96 : 4
+
Ph
OPh
minor
J. F. Hartig, J. Am. Chem. Soc., 125, 3426 (2003)
61
Allylic C-H Alkylation
O
H
COOMe
O
S
S
Ph Pd(OAc)2 Ph
+
Ph
NO2
Pd(II)X2
dioxane/DMSO
DMBQ/AcOH
45 °C, 24 h
oxidant
_
PdX/2
COOMe
Ph
NO2
83%
Pd(0)
COOMe
NO2
Ph
M. C. White, J. Am. Chem. Soc., 130, 14090 (2008)
62
Mizoroki-Heck Reaction
Reviews: de Meijere, Angew. Chem., Int. Ed. Engl., 33, 2379 (1994)
I. P. Beletskaya, Chem. Rev., 100, 3009 (2000)
R1 X
+
cat. Pd (0)
R2
amine
R1
R
2
+
amineH+ X-
R1 = Ar, ArCH2, CH2=CH
O
X = Br, I, OTf, N2+,
Cl
catalyst = Pd(0)
63
Mechanism
d10, 18e
PdL4
HBr +
- 2L
Ar
Ar
Br
PdL2
L
H Pd
8
d10, 14e
Br
d , 16e
L
Ar Pd
Ar
d8, 16e
L
 -elimination
Ar
Br
Pd(L)Br
L
d8, 14e
Ar Pd
olefin insertion
(syn addition)
Br
L
d8, 16e
64
Regioselectivity
R1
2
Br (I)
R
R2
cat. Pd (0)
+
R1
100%
100%
100%
100%
1%
Me
CO2Me
Me
CN
CO2Me
99%
100%
7%
21%
21%
20%
Me
OMe
Me
OMe
MeO
79%
93%
79%
Me
steric and electronic factors direct Ar to least hindered carbon
Bu
80%
65
The First Report
Ph
PdCl2 0.5 mmol
PhI
+
50 mmol
Ph
100 mmol
CH3COOK 60 mmol
CH3OH 1 mol
120 oC, 2 h
Ph
Ph
+
Ph
90%
12%
T. Mizoroki, Bull. Chem. Soc. Jpn., 44, 581 (1971)
Pd(OAc)2 0.2 mmol
PhI
20 mmol
+
Ph
25 mmol
Bu3N 20 mmol
100 oC, 2 h
Ph
Ph
75%
"Mizoroki and coworkers have recently reported a palladium-catalyzed arylation
reaction of olefinic compounds with aryl iodides and potassium acetate in methanol
at 120 oC. We have independently discovered this reaction and find that it can be
carried out under much more convenient laboratory conditions than were used by
Mizoroki and that the reaction provides an extremely convenient method for
preparing a variety of olefinic compounds."
R. F. Heck, J. Org. Chem., 37, 2320 (1972)
66
H
CO2Et
EtO2C
Pd(OAc)2, PPh3
Br
R3SiO
H
K2CO3, MeCN
OSiR3
H
CO2Et
PdX
EtO2C
H
R3SiO
PdX
H
OSiR3
- HPdX
H
syn
addition
syn
elimination
R3SiO
OSiR3
R3SiO
OSiR3
I. Shimizu, J. Org. Chem., 58, 2523 (1993)
67
OMe
DBS
N
Pd(OCOCF3)2/PPh3
H
OBn
toluene, 120 oC
MeO
I
Me
Me
OBn
N
Me
DBS
Me
Me
N
OMe
PdX
DBS
H
syn addition
syn elimination
O OH
N
(-)-morphine
Me
N
L. E. Overman, J. Am. Chem. Soc., 115, 11028 (1993)
68
N
N
I
OTBS
Pd(OAc)2
N
2N HCl
THF
Bu4NCl, DMF, K2CO3
70 °C
H
O
H
H
O
N
isostrychine
N
N
O
H
OH
71%
N
O
N
H
Pd+
H
H
H
H
O
strychine
OH
V. H. Rawal, J. Org. Chem., 59, 2685 (1994)
69
Asymmetric Mizoroki-Heck Reaction: Intramolecular
Ref: M. Shibasaki, J. Am. Chem. Soc., 118, 7108 (1996)
and references cited therein.
pioneer works
COOMe
I
Pd(OAc)2 / (R)-BINAP
Ag2CO3
O
60 °C
NMe
COOMe
PdI
COOMe
H
46% ee
COOMe
H
H
PdI
M. Shibasaki, J. Org. Chem., 54, 4738 (1989)
70
OTf
Pd(OAc)2 / DIOP
benzene, rt
O
Pd
+
O
45% ee
Pd+
O
O
L. E. Overman, J. Org. Chem., 54, 5846 (1989)
cf. L. E. Overman, J. Am. Chem. Soc., 125,
6261 (2003)
71
Asymmetric Mizoroki-Heck Reaction: Intermolecular
Pd(OAc)2 / (R)-BINAP
6 mol%
3 mol%
OTf
+
O
X
+
O
i
Pr2NEt (3 equiv)
X
X
30-40 °C
1 equiv
O
5 equiv
71-89%
>90%ee
29-11%
50-60%ee
TfO is necessary, racemic products observed for idodide
Reaction are very slow, 22-72 h
F. Ozawa, T. Hayashi, J. Am. Chem. Soc., 113, 1417 (1991)
72
+
P
*
P
Pd
Pd P
+
P
P
H
Pd P
O
Ar
O
*
+
*
O
Ar
Ar
Ar
O
O
+
*
P
P
OTf
Pd
_
Ar
O
+
P
Pd
O
Ar
P
*
Pd
P
*
+
P
P
H
O
+
*
Pd P
1. Insert
2. -H
3. dissociate
O
Ar
Ar
O
Ar
thermodynamic
73
product
(R)
Asymmetric Mizoroki-Heck Reaction: Intermolecular
OTf
Pd(dba)2 (3 mol%)
+
O
i
Pr2NEt (2 equiv)
O
C6H6, 30 °C, 3 days
1 equiv
3.9 equiv
92% yield
>99%ee
O
No 2,3-isomer detected
Slow reactions (3-7 days)
PPh2 N
But
A. Pfaltz, Angew. Chem., Int. Ed. Engl. 35, 200 (1996)
74
Ph
Cl
+
Ph
cat. Pd2(dba)3 / PBut3
Ph
Cs2CO3
dioxane, 120 °C, 120 h
Ph
80%
TON = 400
MeO
P
MeO
OMe
3
not effective (<2%)
similar cone angle, pKa
G. C. Fu, J. Org. Chem., 64, 10 (1999)
75
A Fluorescence-based Assay
O
O
O
+
X
O
O
O
O
O
Pd(dba)2 / L
NaOAc
1. TFA
2. TMSCHN2, MeOH
MeO
O
DMF, 100 °C
L = PBut3
O
O
X: Br, Cl
L: 40 different P-ligand
X = Br
O
O
PBut2
Fe
X = Cl
L=
PBut2
Fe
J. H. Hartwig, J. Am. Chem. Soc., 121, 2123 (1999)
76
Screening of Homogeneous Catalysts
by Fluorescence Resonance Energy Transfer
Me
O2S
N
N
N
+
N
Me
O2S
NMe2
Br
Boc
N
strong fluorescence
Pd(dba)2/ 70 different ligand
Boc
N
NMe2
N
weak fluorescence
N
J. F. Hartwig, J. Am. Chem. Soc., 123, 2677 (2001)
77
78
O
Recovery of Catalyst
O
KN
Me
O
O
O
OMs
n
Me
O
O
DMF
reflux, 5 h
n = 110
N
n
87%
O
SPh
H
N
HO
H2NNH2, EtOH
Me
reflux, 20 h
O
O
NH2
n
O
O
Pd Cl
SPh
DMF, rt, 14 h
SPh
Me
O
O
H
N
H
N
Pd
Cl
n
O
O
SPh
98%
D. E. Bergbreiter, J. Am. Chem. Soc., 121, 9531 (1999)
79
cat. 1 mol%
PhI
+
Ph
DME, Et3N
115 oC, 6.5 h
Ph
Ph
1st cycle 91%
2nd cycle 95%
3rd cycle 92%
cat. 1 mol%
PhI
+
COOMe
DME, Et3N
115 oC, 2.5 h
Ph
COOMe
1st cycle 85%
2nd cycle 87%
3rd cycle 95%
触媒はジエチルエーテルを加えて沈殿させ、回収
80
Migita-Kosugi-Stille Coupling
Reviews: J. K. Stille, Angew. Chem., Int. Ed. Engl., 25, 508 (1986)
V. Farina, V. Krishnamurthy, W. J. Scott, Org. React., 50, 1 (1998)
P. Espinet, A. M. Echavarren, Angew. Chem. Int. Ed., 43, 4704 (2004)
R
X
+
R'
SnR"3
cat. Pd (0)
R R'
+
X
SnR"3
R = aryl, RC(O), allyl, benzyl, vinyl, Ar, RCXH(COOR')
X = halogen, OTf
R' = H, aryl, Alkenyl, allyl, benzyl, alkynyl, alkyl
catalyst = Pd(0)
81
Mechanism
L4Pd (0)
R'
oxidative
addition
Ar
Br
L
transmetallation
Ar Pd Br
-2 L
SnR"3
L
_ X
L
Ar Pd R'
SnR"3
L
isomerization
Ar Pd L
L
R'
reductive elimination
L2Pd
R R'
cf. P. Espinet, J. Am. Chem. Soc., 128, 14571 (2006).
Reactivity
R C C > RCH CH > Ar >
RCH CHCH2
ArCH2
>
CH3(CO)CH2
>
alkyl
82
The first paper
Br
SnBu3
+
cat. Pd(PPh3)4
+ Bu3SnBr
benzene
100 °C, 20 h
96%
M. Kosugi, T. Migita, Chem. Lett., 301 (1977)
O
+
Ph
Cl
Me4Sn
O
cat. Pd(PPh3)4
benzene
140 °C, 5 h
Ph
+
Me
Me3SnCl
54%
M. Kosugi, T. Migita, Chem. Lett., 1423 (1977)
O
+
Ph
Cl
Me4Sn
O
cat. PhCH2Pd(PPh3)2Cl
HMPA, 65 °C, 10 min
+
Ph
Me3SnCl
Me
89%
J. K. Stille, J. Am. Chem. Soc., 100, 3636 (1978)
83
CO2Me
CO2Me
Pd(dba)2 / 2PPh3
+
Bu3Sn
CO2CH2Ph
CO2CH2Ph
THF
50 °C
Cl
CO2Me
87%
inversion
J. K. Stille, J. Am. Chem. Soc., 106, 4833 (1984)
PdClL2
ButHNOC
N
TMS
N
Br
+
Me3Sn
ButHNOC
TMS
N
N
S
S
65%
benzene
S
S
Pd(PPh3)2Cl2
micrococcinic acid
T. R. Kelly, Tetrahedron Lett., 32, 4263 (1991)
84
SnBu3
+ I
OH
PdCl2(MeCN)2
DMF
25 °C
OH
73%
J. K. Stille, J. Am. Chem. Soc., 109, 813 (1987)
OMe
N
N
TBDMSO
N
N
O
I
+
SnBu3
OMe
PdCl2(MeCN)2
N
N
TBDMSO
TBDMSO
N
toluene
OTBDMS
O
TBDMSO
V. Nair, J. Am. Chem. Soc., 109, 7223 (1987)
N
OTBDMS
>90%
85
TIPSO
MeO
OMe
O
O
N
O
TESO
O
TBSO
O
O
TIPSO
Bu3Sn
O
MeO
OMe
OMe
O
I
O
N
O
TESO
A. B. Smith, III, J. Am. Chem. Soc., 117, 5407 (1995)
O
TBSO
O
O
MeO
O
Rapamycin
86
OH
(-)-Macrolactine A
O
O
HO
A. B. Smith, III, J. Am. Chem. Soc., 120, 3935 (1998)
HO
OTBS
SnBu3
OTBS
O
Bu3Sn
I
I
OH
OH
O
OH
OPiv
OH
TBSO
TBSO
TBSO
Bu3Sn
I
TBSO
87
OMe
Me
TBSO
TIPSO
OMe
NH
Me
OMe
O
I
I
1)
Pd(MeCN)2Cl2
Bu3Sn
SnBu3
Me
DMF/THF
NH
Me
TBSO
OMe
OMe
O
OMe
TIPSO
O
2) CAN THF/H2O
3) aq. HF/CH3CN
Me
HO
TIPSO
NH
Me
(+)-Mycontrienol
O
O
OMe
J. S. Panek, J. Am. Chem. Soc., 120, 4123 (1998)
88
HO
OH
O
OH
NH
O
O
OH
H
NH O O
N
N
NH
O
O
Sanglifehrin A (SFA)
O
K. C. Nicolau, J. Am. Chem. Soc.,
122, 3830 (2000)
OH
I
O
O
HO
SnBu3
O
OH
NH
+
O
O
H
NH O O
N
N
NH
O
O
OH
89
I
O
O
O
I
O
H
N
NH O O
N
NH
O
I
O
Bu3Sn
O
NH O O
NH2
N
NH
O
O
+
HO
O
OH
OH
90
91
R' B
R X
Pd
oxidative
addition
R Pd X
B X
transmetallation
R Pd
R'
- Pd
reductive
elimination
R R'
_
role of base
R Pd
R' B
R Pd
_
_
OR
X
OR
OR
R' B
R' B OR
R Pd
ate complex
OR
R' B
cf. B. P. Carrow, J. F. Hartwig, J. Am. Chem. Soc., 133, 2116 (2011).
C. Amatore, Chem. Eur. J., 18, 6616 (2012).
OH
Et3P
O B
PEt3 (4 equiv)
Rh
Ph
C6D12, 70 °C
Et3P
PEt3
Et3P
Ph
Rh
Et3P
PEt3
J. F. Hartwig, J. Am. Chem. Soc., 129, 1876 (2007).
92
The first paper
cat. Pd(PPh3)4
O
Br
B
+
benzene
NaOEt / EtOH
reflux, 2 h
O
81%
N. Miyaura, A. Suzuki, Tetradedron Lett., 3437 (1979)
Carbonylative coupling
I
Pd(PPh3)4
+ CO +
B
K3PO4
dioxane
rt, 5 h
O
90%
N. Miyaura, A. Suzuki, Bull. Chem. Soc. Jp., 64, 1999 (1991)
93
Alkyl-Alkyl coupling
NC
I
Pd(PPh3)4
+
B
K3PO4
dioxane
60 °C
CN
61%
N. Miyaura, A. Suzuki, Chem. Lett., 691 (1992)
94
Scope of Palladium-Catalyzed Miyaura-Suzuki Cross-Coupling Reaction
Alkyl
Alkyl
B
CH2=CHCH2
I
CH2=CHCH2
B
X
RCH=CH B
RCH=CH X
B
X
RC C B
RC C X
95
Industrial Application
TESO
TESO
H H
CN
OTf
N
O
+
(HO)2B
Pd2(dba)3
aq. KOH, THF
-78 °C → rt
CO2PNB
CN
H H
N
O
CO2PNB
95%
Yasuda, N.; Xavier, L.; Rieger, D. L.; Li, Y.; DeDamp, A. E.; Dolling, U. H.
Tetrahedron Lett. 1993, 34, 3211.
TESO
O
H H Me
OSiMe3
Pd(dba)2
N
O
OTf
CO2PNB
+
THF, H2O, Et3N
30 °C, 2-3 h
(HO)2B
996 g
TESO
H H Me
N
O
Yasuda, N.; Huffman, M. A. et al
J. Org. Chem. 1998, 63, 5438.
O
OSiMe3
CO2PNB
2.00 kg (70%)
96
O
O
X
O
OY
O
Me
O
YO
OMe
OY
OY
OY
OY
O
OY
Me
OY
YO
OAc
OY
OY
OY
O
OY
OY
Palytoxin caboxylic acid
YO
OY
O
YO
Y. Kishi, J. Am. Chem. Soc., 111, 7525 (1989)
MeO
MeO P
O
OY
OY
O
97
Recent Advances in Cross-Coupling Reactions
Cl
Use of
Design of Ligand
OTs
bulky and electron-rich phosphine
N-heterocyclic carbene
For a review on Pd-catalyzed coupling reactions of aryl chlorides:
G. C. Fu, Angew. Chem. Int. Ed., 41, 4176 (2002).
For a review on monoligated Pd species:
U. Christmann, R. Vilar, R. Angew. Chem. Int. Ed., 44, 366 (2005).
98
Room-temperature Miyaura-Suzuki Coupling of Unactivated Aryl Chlorides
Me
Cl
cat. Pd(OAc)2 / L
+
B(OH)2
Me
CsF
dioxane, rt,
94%
PCy2
S. L. Buchwald, JACS, 120, 9722 (1998)
JACS, 121, 9550 (1999)
L=
Me2N
Me
Cl
+
cat. Pd2(dba)3 / PBut3
B(OH)2
Me
Cs2CO3
dioxane, 80 °C, 5 h
86%
active Pd species bears a single PBut3
steric bulk and electron-richness
G. C. Fu, Angew. Chem., Int. Ed., 37, 3387 (1998)
JACS, 122, 4020 (2000)
cf. A review of Pd-catalyzed coupling reactions of aryl chlorides
G. C. Fu, Angew. Chem. Int. Ed., 41, 4176 (2002)
99
Me
Me
Cl
+
(HO)2B
K3PO4
toluene
90 °C, 12 min
Me
increases steric bulk
MeO
PCy2
OMe
prevents cyclometalation
Br
Me
Me
98%
oxygen lone pair may
stabilize Pd complex
increases electron density
in biaryl backbone
Me Me
Me
Me
Me
Me Me
0.2 mol%
Pd(OAc)2
+
(HO)2B
Me
Pd(OAc)2
K3PO4
toluene
110 °, 18 h
Me
Me Me
82%
S. L. Buchwald, Angew. Chem. Int. Ed., 43, 1871 (2004).
J. Am. Chem. Soc., 127, 4685 (2005).
J. Am. Chem. Soc., 129, 3358
100(2007).
PCy2
Pri
iPr
XPhos
MeO
t
Bu
OMs +
Pd(OAc)2
(HO)2B
Pri
MeO
t
Bu
THF, K3PO4
80 °C, 3 h
91%
H. N. Nguyen, X. Huang, S. L. Buchwald, J. Am. Chem. Soc., 125, 11818 (2003).
MeO
OTs
Ni(cod)2/PCy3
+
(HO)2B
MeO
THF, K3PO4
rt, 8 h
86%
Z.-Y. Tang, Q.-S. Hu, J. Am. Chem. Soc., 126, 3058 (2004).
Z.-Y. Tang, Q.-S. Hu, J. Org. Chem., 71, 2167 (2006).
MeO
OMs +
NiCl2(dppe)/PPh3
(HO)2B
toluene, K3PO4
80 °C, 14 h
MeO
80%
101
V. Percec, G. M. Golding, J. Smidrkal, J. Weichold, J. Org. Chem., 69, 3447 (2004).
cf.
Me
Cl
+ HN
cat. Pd2(dba)3 / PBut3
NH
Me
N
NH
o-xylene, 120 °C
88%
Y. Koie (Tosoh Co.), Tetrahedron Lett., 39, 617 (1998)
imidazol-2-ylidene ligand
For a review on N-Heterocyclic Carbenes, see:
W. A. Herrmann, Angew. Chem. Int. Ed. 41, 1290 (2002)
M. G. Organ, Angew. Chem. Int. Ed. 46, 2768 (2007)
N
N
S. P. Nolan, J. Org. Chem., 64, 3804 (1999)
102
Cl
B(OH)2
80%
+
N
N
Pd
CsF
dioxane
rt, 2 h
Me
N
N
Me
573 the highest TON [(mol product)(mol Pd)-1(h)-1] at rt
Gstottmayr, C. W. K.; Bohm, V. P. W.; Herdtweck, E.; Grosche, M.;
Herrmann, W. A. Angew. Chem. Int. Ed. 2002, 41, 1363.
+
Cl
12
Me
Pd(OAc)2
K3PO4
THF/toluene
110 °C, 16 h
Me
Me Me
96%
O
N
(HO)2B
Me
Me
O
Me Me
Me
Me
N
12
Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F.
J. Am. Chem. Soc. 2004, 126, 15195.
103
Me Me
Me
Me
Cl
(HO)2B
+
NaOBut
i
PrOH
rt, 75 min
Me
Me
88%
ArN
NAr
Pd Cl
NMe2
Ar = 2,6-(iPr)2C6H3
NMe2
O
Pd Cl
NMe2
IPr
IPr
IPr
i
PrOH
Pd O
NMe2
H
Pd H
NMe2
[IPrPd(0)]
Navarro, O.; Kelly, R. A.; Nolan, S. P. J. Am. Chem. Soc. 2003, 125, 16194.
104
Alkyl-Alkyl Coupling
R
R
PdLn
R'
H H
H H
R
H H
PdLn
R
H H
R'
X
PdLn
X
undesired
-hydride
elimination
H
M X
R' M
R
+
PdLn
X
105
Alkyl-Alkyl Coupling
Hex
Br + 9-BBN
Dec
Pd(OAc)2/PCy3
K3PO4.H2O
Hex
Dec
THF, rt, 16 h
85%
Netherton, M. R.; Dai, C.; Neuschutz, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 10099.
Hex
Cl + 9-BBN
Dec
Pd2(dba)3/PCy3
CsOH.H2O
o
dioxane, 90 C
48 h
Hex
Dec
83%
Kirchhoff, J. H.; Dai, C.; Fu, G. C. Angew. Chem. Int. Ed. 2002, 41, 1945.
O
NC
5
Br + BrZn
3
O
c
Pd2(dba)3/P( C5H9)3
OEt
THF/NMP, NMI
80 °C, 14 h
NC
3
5
OEt
65%
Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 12527.
106
O
EtO
4
+
Br
Ph Si(OMe)3
PdBr2
PMetBu2
Bu4NF
THF, r.t.
O
EtO
4
Ph
79%
Lee, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 5616.
[(-ally)PdCl]2
Ph PCy(pyrrolidinyl)2
O
EtO
4
Br
+ Bu Sn
3
Me4NF
THF, rt
O
Ph
EtO
4
89%
Tang, H.; Menzel, K.; Fu, G. C. Angew. Chem. Int. Ed. 2003, 42, 5079.
O
EtO
O
4
Br
+
Cp2ClZr
Ph
Pd(acac)2
LiBr
THF/NMP
55 °C, 24 h
ligandless
EtO
Ph
4
99%
Wiskur, S. L.; Korte, A.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 82.
107
O
O
N
s
N
Bu-Pybox
N
Bus
Bus
Ni(cod)2
Br
+
OPh
BrZn
OPh
DMA, r.t., 20 h
62%
Zhou, J.; Fu. G. C. J. Am. Chem. Soc. 2003, 125, 14726.
Ph
Br +
Ni(cod)2
Ph B(OH)2
Ph
N
butanol, KOBut
60 oC, 5 h
N
Ph
s
91%
Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 1340.
Gonzalez-Bobes, F.; Fu, G. C. J. Am. Chem. Soc. 2006, 128, 5360.
Si: Powell, D. A.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 7788.
108 510.
Sn: Powell, D. A.; Maki, T.; Fu, G. C. J. Am. Chem. Soc. 2005, 127,
109
Cross-Coupling of Secondary Nucluophiles with Secondary Propargylic Electrophiles at RT
TIPS
TIPS
NiCl2 . glyme /
+ IZn
Cl
Et
THF, rt
N
N
N
N
N
Et
75%
G. C. Fu, Angew. Chem. Int. Ed., 47, 9334 (2008)
110
Sonogashira Coupling
NC
Br
+
Cl
[(-ally)PdCl]2
CuI, Cs2CO3
DMF/Et2O,
45 °C, 16 h
NC
Cl
74%
G. C. Fu, J. Am. Chem. Soc., 125, 13642 (2003)
cf. A review: H. Doucet and J.-C. Hierso,
Angew. Chem., Int. Ed. 46, 834 (2007)
111
Negishi Coupling
R X
+
Pd(0)
R'
ZnX
R = Ar, vinyl, alkyl
X = I, Br
generaion of Zn reagents
R'MgX + ZnCl2
R'Li + ZnCl2
R'3Al + ZnCl2
R R'
+
ZnX2
R' = Ar, vinyl, alkyl
inert to ketone, esters, amino and
cyano goups
A recent review: E. Negishi, Aldrichimica Acta,
38, 71 (2005).
R' I + Zn(Cu)
D. Cardenas, Chem. Soc. Rev. 38, 1598 (2009).
iodine-zinc exchange
Mechanism: J. A. Casares, P. Espinet, J. Am. Chem.
Soc. 129, 3508 (2007).
112
Pd(0)
R X
+
R' SiY3
R R'
+
Y3Si X
Y = Cl, F, H, OMe, cyclobutyl, thienyl, OH .....
R = Ar, vinyl, alkynyl, allyl
R' = Ar, vinyl, allyl, alkynyl
X = I, Br, OTf
review: Hiyama, T. Topp. Curr. Chem. 2002, 219, 61.
D. R. Spring, Chem. Soc. Rev., 41, 1845 (2012).
[( 3-C3H5)PdCl]2
(Et2N)3S+Me3SiF2- (TASF)
I
+
SiMe3
HMPA, 50 °C, 2 h
98%
Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918.
Review: Denmark, Regens, C. S. Acc. Chem, Res. 2008, 41, 1486.
Nakano, Y.; Hiyama, T. J. Am. Chem. Soc. 2005, 127, 6952.
113
Tamao-Kumada-Corriu Coupling
+
R X
R' MgX
NiCl2(dppp)
R R'
+
MgX2
PPh2
R = Ar, vinyl, benzyl R' = Ar, vinyl, ally, alkyl
X = I, Br, Cl
RX
L2Ni
L2Ni
L2NiR'2
2MgX2
PPh2
oxidative addition
2R'MgX
L2NiX2
dppp =
R'MgX
R' R'
reductive
elimination
R
X
transmetalation
R R'
L2Ni
R
R'
MgX2
114
The first reports
Cl
Et
+
EtMgBr
NiCl2(dppe)
Et2O
reflux, 20 h
98%
Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972, 94, 4374.
Ph
Br
+
PhMgBr
Ni(acac)2
Et2O, rt
Ph
Ph
70%
Corriu, R. J. P.; Masse, J. P. J. Chem. Soc., Chem. Commun. 1972, 144.
115
BuBr + Mg
Cl
+
Cl
29.5 g
BuMgBr
Mg (12.2 g, 0.50 mol)
Et2O (200 mL)
1-bromobutane (68.5 g, 0.5 mol) in Et2O (50 mL)
NiCl2(dppp)
Bu
Et2O
0 °C → reflux
6h
Bu
79-83%
(30.0-31.5 g)
NiCl2(dppp) (0.25 g, 0.5 mmol)
1,2-dichlorobenzene (29.5 g, 0.21 mol)
Et2O (150 mL)
Kumada, M.; Tamao, K.; Sumitani, K. Org. Synth. 1988, Coll. Vol. 6, 407.
cf. Buck, J. R.; Park, M.; Wang, Z.; Prudhomme, D. R.; Rizzo, C. J.
Org. Synth. 1999, Vol. 77, 153.
Organic Synthesis Website: http://www.orgsyn.org/
116
NiCl2/L*
+
Ph
Br
MgCl
PPh2
H
O
O
Fe
PPh2
PPh2
NMe2
R
H
Me2N
PPh2
R = iPr
R = tBu
81% ee
94% ee
H Me
H
(-)-DIOP
<16% ee
Ph
Ph *
Et2O
0 °C, 2 d
(S)-(R)-PPFA
63% ee
MgCl
(R)
Ph
Valphos
t-Leuphos
MgCl
(S)
Hayashi, T.; Konishi, M.; Fukushima, M.; Kanehira, K.; Hioki, T.; Kumada, M.
J. Org. Chem. 1983, 48, 2195.
117
i
Pr
H
Me2N
MgCl
PPh2
NiCl2
*
H2C CHBr
Et2O, 0 °C
[O]
* COOH
ibuprofen 81%ee
Hayashi, T.; Konishi, M.; Fukushima, M.; Mise, T.; Kagotani, M.; Tajika,
M.; Kumada, M. J. Am. Chem. Soc. 1982, 104, 180.
118
PhCH2
H
Me2N
TfO
OTf
PPh2
Pd
Cl2
PhMgBr/LiBr
Et2O/toluene
- 30 °C, 40 h
Ph
OTf
Ph
Ph
+
87% (93%ee)
Ph
13%
PPh2
Hayashi, T.; Niizuma, S.; Kamikawa, T.; Suzuki, N.; Uozumi, Y.
J. Am. Chem. Soc. 1995, 117, 9101.
119
Ph
OMe
+
PhMgBr
NiCl2(PPh3)2
C6H6
rt, 72 h
70%
Wenkert, E.; Michelotti, E. L.; Swindell, C. S.; Tingoli, M.
J. Org. Chem. 1984, 49, 4894.
Ph
OMe
+
PhMgBr
NiCl2(PPhCy2)2
t
AmOMe/Et2O
23 °C, 15 h
91%
Dankwardt, J. W. Angew. Chem., Int. Ed. 2004, 43, 2428.
120
Iron-Catalyzed Grignard Cross-Coupling
O
OMe
THF/NMP
0 °C → rt, 5 min
X
X = Cl: C6H13MgBr (91%)
C6H13MgBr:
N
N
O
Fe(acac)3
RMgBr
OMe
R
PhMgBr (28%)
MgBr
MgBr
X = Cl (91%) OTf (87%) OTs (83%) Br, I (<40%)
Cl
Fe(acac)3
RMgBr
THF/NMP
0 °C → rt, 5 min
N
R
N
MgBr
(82%)
RMgBr: C14H29MgBr (95%) PhMgBr (73%)
N
S
MgBr
(69%)
Furstner, A.; Leitner, A.; Mendez, M.; Krause, K. J. Am. Chem. Soc. 2002, 124, 13856.
Furstner, A.; Leitner, A. Angew. Chem. Int. Ed. 2002, 41, 609.
121
NiCl2(dppp)
C4H9MgBr
TfO
N
Cl
Et2O
reflux, 6 h
C4H9
N
C4 H9
63%
Fe(acac)3
C6H13MgBr
TfO
N
Cl
THF/NMP
0 °C, 5 min
C6H13
N
C6H13
73%
Fe(acac)3
1) Me2CHCH2MgBr
2) C14H29MgBr
TsO
N
Cl
N
THF/NMP, 0 °C
1) 3 min
2) 5 min
71%
122
RCH2CH2CH2CH2R
Fe
4 RCH2CH2MgX
+
RCH CH2
+
RCH2CH3
MgX2
RX
[R Fe(MgX)]
[Fe(MgX)2]
FeCl2
cf. A. Furstner, J. Am. Chem. Soc.,
130, 8773 (2008)
R R'
R'MgX
R'
[R Fe(MgX)2]
RX
Ni
2R'MgX
L2NiX2
L2Ni
L2Ni
L2NiR'2
2MgX2
R
X
R'MgX
R' R'
R R'
L2Ni
R
R'
MgX2
123
MeOOC
O
MgCl. LiCl
PCy 2
NMe 2
Pd(dba)2
MeOOC
+
O
toluene/THF, -20 °C
I
N
Boc
86%
N
Boc
Cl
Cl
Cl
N
O
Cl
S
Cl
O
S
O
F 3C
55%
O
73%
86%
Buchwald, S. L.; Martin, R. J. Am . Chem . Soc. 2007, 129, 3844.
124
Generation of Ar-Pd-X Species
Pd(0)
Ar
X
Ar
O
Ar
PdX
PdX2
Ar
OH
+ HX + CO2
PdX
A. G. Myers, J. Am. Chem. Soc., 124,
11250 (2002). J. Am. Chem. Soc. 127,
10323 (2006).
O
MeO
MeO
OH
OMe
+
Ph
Pd(O2CCF3)2, Ag2CO3
DMSO-DMF, 120 °C
1h
MeO
MeO
Ph
OMe
DFT study: L. Liu, J. Am. Chem. Soc., 132, 638 (2010).
125
Generation of Ar-Pd-X Species
O
Ar
P
OH
P
O
Ar
PdX
+
OH
O
Ar
PdX2, F-
OH
O-
-
F
Ar
P
OH
F
OH
PdX2
OH
- X-
F P
OH
OH
H. Shinokubo, K. Oshima,
J. Am. Chem. Soc., 125, 1484 (2003)
XPd O
Ar
P
F
OH
OH
O
Ar
PdX + F P
OH
OH
O
P OH
OH
MeO
+
Ph
Ph
Pd(OAc)2, M3NO, TBAF
dioxane, 100 oC
24 h
MeO
100%
126
O
O2N
Cu2O, PdI2
1,10-phenanthroline, Tol-BINAP
OK
+
NMP, 170 °C, 24 h
TfO
CuX2Phen
Pd(0)
O2N
O
O2N
OCuX
72%
Pd
OTf
-CO2
O2N
CuX
L. J. Goossen, J. Am. Chem. Soc., 130, 15248 (2008)
127
Carbene Complex
M
C
(1) Schrock carbenes

But
Ta 
t
Bu
But
O
O
+
Ph
t
Ta
Me
Bu
Ph
Me
O
Ta
Ph
Me
+
But
But
R. R. Schrock, J. Am. Chem. Soc., 98, 5399 (1976)
(2) Fischer carbenes
  OMe
(OC)5Cr C
Me
BuLi
_
(OC)5Cr
OMe
C
OMe
O
(OC)5Cr
C
O-
O
(OC)5Cr
C
CH2
C. P. Casey, J. Organomet. Chem., 102, 175 (1975)
128
(3) Grubbs catalyst
Cl
Cl
PCy3
Ru
RCM = Ring-Closing Metathesis
ROMP = Ring-Opening Metathesis Polymerization
Ph
PCy3
Ph
(4) Carbenoid
R
COOMe LnRh(II) or LnCu(I)
N2
- N2
R
R
COOMe
R
COOMe
COOMe
MLn
R'
H
R'
H
Review: A. Padwa, Angew. Chem., Int. Ed., 33, 1797 (1994)
J. Adamas, Tetrahedron, 47, 1765 (1991)
M. A. McKervey, Chem. Rev., 94, 1091 (1994)
129
R1
R1
M2+
M C
Schrock Carbenes
2-
R2
R2
R1, R2 = H, alkyl
PMe3
CH2
Cp2TaV
But
CH3
t
Bu
W
But
PMe3
Tebbe Olefination
Cp2TiCl2 + 2 AlMe3
Review: Schrock, Acc. Chem. Res., 19, 342
(1986)
H2
C
Cp2Ti
Cl
py
AlMe2
Cp2Ti
CH2
+ py AlMe2Cl
O toluene, -15 °C
→ rt
Tebbe's reagent
F. N. Tebbe (du Pont), J. Am. Chem. Soc.,
100, 3611 (1978)
CH2
65%
130
O
Cp2Ti
CH2
+
X
R
O
R
Cp2Ti
X
X = Cl
X
R
R. H. Grubbs, J. Am. Chem. Soc.,
102, 3270 (1980)
O TiClCp2
R
CH2
X = H, R, OR, NR2
OH
R'CHO
O
R'
R
R. H. Grubbs, J. Am. Chem. Soc., 105, 1664 (1983)
131
O
BnO
O
BnO
OBn
BnO
O
OBn
BnO
OBn
OBn
T. V. Rajanbabu (du Pont), J. Org. Chem., 51, 5458 (1986)
OTBS OBn
OTBS
EtO2C
OTBS OBn
1. Swern oxidation
CH2OH 2. Tebbe's reagent
OTBS OBn
OTBS
EtO2C
OTBS
S. L. Schreiber, J. Am. Chem. Soc., 112, 9657 (1990)
OTBS OBn
OTBS
Hizikamcin
132
Petasis reagent
O
Cp2TiCl2 + 2 MeLi
Cp2TiMe2
toluene
or THF
60-65 °C
O
Ph
O
O
C
H2
+
CH2
H
+
CH4
O
O
O
Ph
OMe
Ph
O
O TiCp2
Cp2
Ti
O
CH3
O
O
O
N. A. Petasis, J. Am. Chem. Soc., 112, 6392 (1990)
mechanistic evidence for discrete carbene mechanism
-elimination
Cp2TiMe2
Cp2Ti
CH2
133
CH2Br2 + TiCl4 + Zn-Pb
O
CH2Br2
TiCl4/Zn
THF
25 °C
89%
K. Oshima, Tetrahedron Lett., 2417 (1978)
O
COOMe
CH2Br2
TiCl4/Zn
COOMe
THF
THPO
THPO
OTHP
OTHP
80%
S. Ikegami, Tetrahedron Lett., 24, 3493 (1983)
134
O
CH2I2
TiCl4/Zn
THF
25 °C, 15 min
88%
K. Takai, Tetrahedron Lett., 26, 5579 (1985)
Ph
Bu
BuCHBr
TiCl4/Zn/TMEDA
O
OEt
THF
25 °C
Ph
OEt
82% (Z/E = 93/7)
K. Takai, J. Org. Chem., 52, 4410 (1987)
135
OMe
Fischer Crabene
(OC)5Cr
C
R
Preparation
_
Cr(CO)6 + RLi
_
(OC)5Cr
O
O
(OC)5Cr
C
R
C
_
Me3O+ BF4
OMe
(OC)5Cr
C
R
R
E. O. Fischer, Angew. Chem., 3, 580 (1964)
136
Elaboration
BF3.OEt2
OMe
(OC)5Cr
C
_
BuLi
(OC)5Cr
OMe
C
OMe
O
(OC)5Cr
_
O
O
C
(OC)5Cr
C
CH2
Me
pKa = 8
C. P. Casey, J. Organomet. Chem., 102, 175 (1975)
OMe
(OC)5Cr
C
Et
(CO)5Cr
BuLi
Et2O
-78 °C
PhCHO, TiCl4
CH2Cl2
-78 °C, 1 h
(CO)5Cr
OH
MeO
Ph
OH
+
MeO
Me
Ph
Me
55% (86 : 14)
W. Wulff, J. Am. Chem. Soc., 107, 503 (1985)
137
Elaboration
OMe
(OC)5W C
_ Ph
(OC)5W C OMe
PhLi
Ph
HCl
(OC)5W C
Ph
Ph
Ph
Casey carbene
C. P. Casey, J. Am. Chem. Soc.,
99, 2127 (1977)
(also amines, mercaptanes, etc)
cf. E. O. Fischer, Chem. Ber., 106, 1277 (1973)
OLi
OMe
(OC)5Cr
+
OMe
(OC)5Cr
O
82%
C. P. Casey, J. Organomet. Chem., 77, 345 (1974)
138
Elaboration
OMe
+
(OC)5Cr
25 °C
3 min
OMe
MeO
Cr(CO)5
78% (endo/exo = 94/6)
much faster than O
(104)
W. Wulff, J. Am. Chem. Soc., 105, 6726 (1983)
OMe
(OC)5Cr
TMSO
TMSO
+
OMe
Me
benzene
25 °C
10 min
Me
Cr(CO)5
OMe OMe
100%
W. Wulff, J. Am. Chem. Soc., 106, 7565 (1984)
139
Review: K. H. Dötz, Angew. Chem., 23, 587 (1984)
Dötz Reaction
OH
OMe
(OC)5Cr
RL
+
RL
RS
RS
(OC)3Cr
OMe
A first report
OMe
(OC)5Cr
OH
OH
Ph
Ph
Ph
Bu2O
45 °C
Ph
CO (40 atm)
Ph
Ph
(OC)3Cr
OMe
62%
OMe
80%
K. H. Dötz, Angew. Chem., 14, 644 (1975)
140
Cr(CO)5
MeO
R
- CO
R'
Cr(CO)4
MeO
MeO
R
(CO)4
Cr
CO
Cr(CO)4
R'
O
MeO
C
O
MeO
R
R
O
(OC)3Cr
OMe
R'
R'
Cr(CO)3
OH
R'
R'
R
R
(OC)3Cr OMe
141
Natural Product Synthesis
1.
OMe
(OC)5Cr
OMe O
THF, 45 °C
OH
O
2. [Fe(DMF)3Cl2][FeCl4]
O
O
O
O
OMe
O
OH
OMe O
OH
O
O
OH
OH
OMe
O
O
O
COH
OMe O
OMe
W. Wulff, J. Am. Chem. Soc., 106, 434 (1984)
142
Ring-Closing Metathesis (RCM) Catalyst
Review: R. H. Grubbs, Acc. Chem. Res., 28, 446 (1995)
S. K. Armstrong, J. Chem. Soc., Perkin I, 371 (1998)
A. Fürstner, Angew. Chem. Int. Ed., 39, 3013 (2000)
Y. Schrodi, Aldrichimica Acta, 40, 45 (2007)
F. Verpoort, Chem. Rev., 110, 4865 (2010)
Pri
Cl
N
(F3C)2MeCO
i
Pr
Mo
(F3C)2MeCO
Cl
PCy3
Ru
Ph
PCy3
Cl
Cl
PCy3
Ru
PCy3 Ph
Ph
CHCMe2Ph
2
3
1
1 Schrock, J. Am. Chem. Soc., 112, 3875 (1990)
2 R. H. Grubbs, J. Am. Chem. Soc., 115, 9858 (1993)
3 R. H. Grubbs, Angew. Chem., Int. Ed. Engl.34, 2039 (1995)
143
Pri
O
Ph
(F3C)2MeCO N Pri
Mo
(F3C)2MeCO CHCMe2Ph
O
Ph
H3CHC CHCH3
+
benzene, 20 °C, 15 min
O
O
+
_
M
O
M
M
O
O
- CH2=CH2
M
CH2=CH2
M
R. H. Grubbs, J. Am. Chem. Soc., 114, 5426 (1992)
144
N COOBut
PCy3
Cl
Ru
Cl
PCy3
Ph
Ph
N COOBut
benzene, 20 °C, 1 h
93%
O
O
Ph
Ph
O
5h
O
O
Ph
1h
O
87%
86%
Cl+
N
H
NaOH
Ph
N
CH2Cl2
20 °C, 36 h
Ph
79%
R. H. Grubbs, J. Am. Chem. Soc., 115, 9856 (1993)
145
Ph
O
O
OH
H
H
O
O
O
O
OR
H
O
O
H
( -)-gloeosporone
OR
O
O
H
OR
O
O
H
A. Fürstner, J. Am. Chem. Soc., 119, 9130 (1997)
A review on metathesis in total synthesis:
A. Fürstner, Chem. Commum., 47, 6505 (2011).
146
NHTf
OMe
O3, MeOH, p-TsOH
H
MeO
NaHCO3, Me2S
NHTf
O
Ti(OPri)4 (1.2 eq.)
82%
OMe
OH
Zn(pent)2
4-pentenoyl chloride
MeO
DMAP, pyridine
88% (>98%ee)
O
OMe
O
O
CF3COOH
O
O
H
MeO
91%
90%
147
SnBu3
OH
(S)-BINOL (20 mol%)
O
O
TBDMSCl, imidazole
Ti(OPri)4 (10 mol%)
Cl
Cl
77% (>98% de)
PCy3
O
(3 mol%)
Ru
PCy3 Ph
H
i
Ti(OPr )4 (30 mol%)
OR
O
O
KMnO4, Ac2O
O
OR
CH2Cl2, 40 oC
H
80% (Z:E = 2.7:1)
O
H
O
O
H
OH
aq. HF
MeCN
H
O
54%
O
O
(-)-gloeosporone
H
148
BnO
BnO
BnO
O
O
TiCl4, Zn
TMEDA, CH2Br2
PbCl2 (cat.)
BnO
BnO
BnO
Pri
N Pri
(F3C)2MeCO
Mo
(F3C)2MeCO CHCMe Ph
2
O
BnO
BnO
BnO
O
68%
M. H. D. Postema, J. Org. Chem., 64, 1770 (1999)
cf. R. H. Grubbs, J. Org. Chem., 59, 4029 (1994)
149
PCy3
Cl
Ru
Cl
R. H. Grubbs, Angew. Chem., Int. Ed. Engl.34, 2039 (1995)
PCy3
Ph
1st generation catalyst
Pri N
Cl
N Pri
W. A. Herrmann, Angew. Chem. Int. Ed. 37, 2490 (1998)
Ru
Cl
Pr
i
Ph
i
N Pr
N
Mes N
Cl
N Mes
1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligand
Ph
R. H. Grubbs, Org. Lett., 1, 953 (1999)
R. H. Grubbs, J. Am. Chem. Soc., 122, 3783 (2000)
Ru
Cl
PCy3
2nd generation catalyst
A recent review: R. H. Grubbs, Chem. Rev., 110, 1746 (2010)
150
ROMP (Ring-Opening Metathesis Polymerization)
O
O
NMe
PCy3
Cl
Ru
Cl
PCy3Ph
O
CH2Cl2, H2O
DTAB
O
O
N
Me
O
n
R. H. Grubbs, J. Am. Chem. Soc., 118, 784 (1996)
water-soluble Ruthenium alkylidene complexes
Me2+ ClN
NMe3+Cl-
P
Cl
catalyzed ROMP of strained,
cyclic olefins in water
P
Cl
Ru
Cl
P
R. H. Grubbs, J. Am. Chem. Soc., 122, 6601 (2000)
Ru
Cl
Ph
NMe3+Cl-
P
Ph
N
Me2+ Cl-
J. Am. Chem. Soc., 123, 3187 (2001)
151
Recyclable Catalyst
Me
Me
Me
Me
Cl
O
Me
N2
O
H
CH2Cl2
90%
OBn
O
H
CH2Cl2
-78 °C
Me Cl Cl
Me O Ru PCy3
H
Me
Cl
Ru PCy3
PCy3
RuCl2(PPh3)3
H
Cl
Cl
Ru PPh3
OBn
75%
recovered catalyst 89%
by silica gel chromatography
A. M. Hoveyda, J. Am. Chem. Soc.,
121, 791 (1999)
CH2Cl2, 22 °C, 2 h
95%
152
Recyclable Catalyst
Me
Cl
Me
O
Cl
Ru
H
Mes
N
N
Mes
O
O
commercial CH2Cl2
at 22 oC in air
O
59% conversion
SiMe2
ring-opening/cross metathesis
glass-bound metathesis catalyst
J. T. Fourkas, A. M. Hoveyda, Angew. Chem., Int Ed.
40, 4251 (2001)
153
permanently immobilized metathesis catalyst
M. R. Buchmeiser, Angew. Chem. Int. Ed., 40, 3839 (2001)
154
Sustainable Concepts in Olefin Metathesis
Mes N
N Mes
Mes N
Mes N
N Mes
N Mes
Cl Ru
Cl
Cl Ru
Cl
Cl Ru
Cl
O
O
O
_
SO3
+
NEt2H
_
+N
PF6
N
A review: S.P. Nolan, Angew. Chem. Int. Ed., 46, 6786 (2007)
cf. Polymer-Supported Well-Defined Metathesis Catalyst
M. R. Buchmeiser, Chem. Rev. 109, 303 (2009).
155
Asymmetric Ring-Closing Metathesis
Me
OTES
Me
Me
Me
Me
i
t
Pr
Bu
O N Pri
Mo
O CHCMe2Ph
But
Me
SETO
OTES
H
Me
H
+
+
Me
benzene, 22 °C, 10 min
Me
43%
93%ee
dimer
38%
19%
>99%ee
krel = 58
R. R. Schrock, J. Am. Chem. Soc., 120, 4041 (1998)
cf. R. R. Schrock, J. Am. Chem. Soc., 118, 2499 (1996)
156
O
O
C6H6, 50 oC, 4 h
87%
96%ee
A. H. Hoveyda, J. Am. Chem. Soc., 123, 3139 (2001)
157
AROM
R
O
RCM
R
A
MoLn
R
R
O
O
R
RCM
AROM
O
LnMo
O
ent-A
MoLn
R
O
A or ent-A
158
Enyne Metathesis
OAc
A recent review: C. Bolm, Chem. Soc. Rev.,
6, 55 (2007)
PCy3
Cl
Ru
Cl
PCy3
OAc
Ph
Ph
TsN
TsN
benzene, rt, 40 min
86%
M. Mori, Synlett, 1020 (1994)
O
PCy3
Cl
Ru
Cl
PCy3 Ph
CH2Cl2, rt,
Ph
O
Ph
6 % (under Ar)
96% (under ethylene)
M. Mori, J. Org. Chem., 63, 6083 (1998)
159
Alkyne Metathesis
O
O
A review: A. Fürstner, Chem. Commun. 2307 (2005)
O
O
O
O
W(
CCMe3)(OCMe3)3
O
O
+
C6H5Cl, 80°C
73%
O
O
O
97%
A. Fürstner, Angew. Chem., Int. Ed.,37, 1734 (1998)
A. Fürstner, Chem. Eur. J., 7, 5299 (2001)
O
160
O
O
Mo(
O
CH)(NBut(3,5-Me2C6H3)3
O
O
TBSO
CH2Cl2, 80 °C
O
TBSO
cis-alkene
1) H2, Lindler
O
2) HF, CH3CN
O
O
PGE2
TBSO
A. Fürstner, Angew. Chem., Int. Ed., 39, 1234 (2000)
J. Am. Chem. Soc., 122, 11799 (2000)
161
O
O
[Cp*Ru(MeCN)]PF6
O
O
O
HSi(OEt)3
O
O
CH2Cl2, rt
O
O
O
O
AgF
O
O
THF/MeOH
rt
O
O
O
trans-alkene
Si(OEt)3
93% (Z/E = 95/5)
A. Fürstner, Tetrahedron, 60, 7315 (2004)
162
163
O
O
Ph
O
O
HN
Ph3SiO Mo OSiPh3
OEt2
Ph3SiO
MeO
OMOM
toluene, rt
79%
O
O
A. Furstner, J. Am. Chem. Soc., 132, 11045 (2010).
164
An Endless Route to Cyclic Polymer
N
N
Cl
n
Ru
Cl PCy Ph
3
直鎖高分子
n
n
水素化
N
N
Cl
Ru
Cl
PCy3
n
n-1
n-1
環状高分子
R. H. Grubbs, Science, 297, 2041 (2002)
J. Am. Chem. Soc. 131, 2670 (2009)
165
ROMP
Ar
N
N
Cl
Ru
Cl
Ar
Ar
N
PCy3
N
Ar
Ar
N
Ru
Ar
Ru
Ru
Ar
N
N
N
Ar
Ar
N
N
Ar
Ru
166
N
N
Cl
Ar
Ru
Cl
n
PCy3
N
N
Ar
N
N
Ru
Ru
n
n
n
Ar
N
N
Ru
n
Ar
N
N
n
Ru
n-1
167
Carbenoid Reactions
Review: M. A. KcKervey, Chem. Rev., 94, 1091 (1994)
A. Padawa, Angew. Chem., Int. Ed. Engl., 33, 1797 (1994)
C. A. Merlic, Synthesis, 1137 (2003)
M. S. Sanford, Tetrahedron, 62, 2439 (2006)
H. M. L. Davies, Chem. Soc. Rev., 40, 1857 (2011)
R1
RO2C
R'
RO2C
N2
LnRh(II) or LnCu(I)
- N2
RO2C
R1
MLn
R2 H
OR3
RO2C
RO2C
R2
R1
OR3
168
R1
H
Rh(II)-Catalyzed C-H Insertion Reactions
O O OO
Rh
Rh
O
EtO2C
H
O
O
O
[Rh(OAc)2]2
EtO2C
N2
O
O
CO2Et
N2
R
CO2Et
R
D. F. Taber, J. Org. Chem., 47, 4808 (1982)
D. F. Taber, J. Am. Chem. Soc., 107, 196 (1985)
169
Rh2L4
N2
Ph
H
+
O
O
O
L = OAc
L = C3F7CO2 (pfb)
67
33
0
100
100
0
O
L=
N
A. Padawa, J. Am. Chem. Soc., 115, 8669 (1993)
(cap)
170
Regioselectivity
[Rh(OAc)2]2
O
N2
O
O
O
J. Adams, Tetrahedron Lett., 28, 4773 (1987)
O
O
N2
[Rh(OAc)2]2
OMe
OMe
n
n = 1 : 83%
n = 2: 81%
n
O
O
G. Stork, Tetrahedron Lett., 29, 2283 (1988)
O
O
O
N2
O
COMe
[Rh(OAc)2]2
O
O
OH
O
COMe
T. Durst, J. Chem. Soc., Chem. Commun., 1150171
(1987)
Insertion into Heteroatom-H Bonds
O
[Rh(OAc)2]2
O
O
N2 CO2Et
OH
CO2Et
C. J. Moody, J. Chem. Soc., Perkin 1, 721 (1989)
OH
H H
O
NH
N2
O
[Rh(OAc)2]2
CO2Bn
OH
H H
O
N
Tienamycin
O
CO2Bn
P. J. Reider, Tetrahderon Lett., 23, 2293 (1982)
O
O
H
Ph
N2
[Rh(OAc)2]2
+ HSiEt3
Ph
SiEt3
M. P. Doyle, J. Org. Chem., 53, 6158 (1988)
172
Enantioselective O-H Insertion
O
O
Ph
OMe +
Cu(OTf)2, (+)-1
Me3Si
OH
ClCH2CH2Cl, H2O
rt, 1 h
N2
Ph
OMe
Me3SiCH2CH2O H
94% (90%ee)
Me
Me
Me
Me Fe
Me
N
Fe
Me
Me
N
O
Me
Me
Me
BF3.Et2O
CH2Cl2, rt
(+)-1
Ph
OMe
HO H
G. C. Fu, J. Am. Chem. Soc. 128, 4594 (2006).
BocNH2: G. C. Fu. J. Am. Chem. Soc., 129, 12066 (2007).
Phenol/bisoxazoline: Q.-L. Zhou, J. Am. Chem. Soc. 129, 12616 (2007).
173
Intramolecular Asymmetric Cyclopropanation
R1
R1
2
R
N2
Rh2(MEPY)4
O
H H
2
R
O
R1 = H, R2 = H, Ar, alkyl
R1 = H, R2 = H
O
>94%ee
65-75%ee
5-MEPY =
O _ N
CO2Me
M. P. Doyle, S. F. Martin, and P. Muller, J. Am. Chem. Soc., 113, 1423 (1991)
S. F. Martin, Tetrahedron, 49, 3521 (1993)
M. P. Doyle, Tetrahedron, 50, 1665 (1994)
174
Asymmetric C-H Insertion
O
O
N2
O
Rh2(MEPY)4
R = OMe
R = Ph
O
91%ee
46%ee
R
R
M. P. Doyle, J. Am. Chem. Soc., 113, 8982 (1991)
H
N2
H
O
n
O
O
nH
O
+
O
nH
Rh2(MEPY)4
3-4 : 1
Rh2(MACIM)4
99 : 1 (96-97%ee)
O
MeOC
N
4S-MACIM =
O _ N
CO2Me
M. P. Doyle and P. Muller, J. Am. Chem. Soc.,
116, 4507 (1994)
175
CO2Me
+
N2
Ph
CO2Me
+
N2
Ph
O
+
Ar, degassed
10 oC
Ph
Ar, degassed
-10 oC
CO2Me
Ph
Ar, degassed
-50 oC, hexane
H O
Rh
O
Rh
4
N
SO2Ar
80% (95%ee)
Ar = p-(C11H23)C6H4
Rh2(S-DOSP)4
CO2Me
Rh2(S-DOSP)4
1 mol%
Rh2(S-DOSP)4
1 mol%
N2
CO2Me
Rh2(S-DOSP)4
1 mol%
Ph
20% (75%ee)
CO2Me
O
Ph
(97%ee)
H. M. L. Davies, J. Am. Chem. Soc., 122, 3063 (2000)
176(2003)
cf. H. M. L. Davies, J. Am. Chem. Soc., 125, 6462
Boc
O
N
1
0.66
2700
1700
Ph2ButSi
28,000
0.011
0.078
H
24,000
Relative Rates of Reaction with Various Substrates
approach from front
H
MeO2C
Ar
NBoc
+
H
Ar
MeO2C
Rh
H
NBoc
Rh
MeO2C
Ar
H
177
cf. DFT calculation: E. Nakamura, Adv. Synth. Catal., 345, 1159 (2003).
[2,3]-Sigmatoropic Rearrangement
O
O
COOMe
O
N2
Rh2(S-PTTL)4
toulene, 0 °C
COOMe
O
70 %, 74%ee
O
O
O
t
Bu
COOMe
N
H
O
O
O
Rh
Rh
Rh2(S-PTTL)4
O
Rh
+
O
COOMe
_
Rh
S. Hashimoto, Tetrehedron Lett., 42, 6361 (2001).
178
C-H Amination
H
N
H2N
Rh2(OAc)4
O
O
PhI(OAc)2, MgO
CH2Cl2, 40 °C, 12 h
O
PhI
86%
(AcO)4Rh2
N
O
N
O
O
O
O
J. Du Bois, Angew. Chem., Int. Ed., 40, 598 (2001).
Ts
O O
S
H2N
O
HN
O
COOMe
J. Du Bois
J. Am. Chem. Soc., 123, 6935 (2001)
O
no PhI(OAc)2
H. Lebel.
J. Am. Chem. Soc., 127, 14198 (2005).
179
Enantioselective C-H Amination
Ts
H
O
H2N
O
S
O
N
O
Rh
H
N
Rh
O
HN
O
S
O
PhI=O, CH2Cl2
85% (92%ee)
D. N. Zalatan, J. Du Bois, J. Am. Chem. Soc., 130, 9220 (2008).
180
Asymmetric C-H Amination
O
H
N
O
O
NTs
S
+
_
(+)
NH2
O
Rh
O
Rh
O (R)
NTs
S
NH
p-Tol
PhI(OCOBut )2
Cl2CHCHCl2/MeOH
-35 °C
77% (98%de, 98%ee)
P. Mullerm R. H. Dodd, P. Dauban, J. Am. Chem. Soc., 130, 343 (2008).
Review: P. Dauban, Chem. Soc. Rev., 40, 1926 (2011).
Y. Shi, Chem. Soc. Rev., 41, 931 (2012).
181
182
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