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15:35-
第９族金属アニオン錯体を鍵活性種とする炭素―炭素結合形成反応
Carbon-Carbon Bond Formations by Anionic Group 9 Metal
Complexes
岩
孝紀 先生
Dr. Takanori Iwasaki
講演者プロフィール
岩 孝紀（いわさき たかのり）
大阪大学 大学院工学研究科 応用化学専攻 助教
2004年 大阪大学基礎工学部化学応用科学科卒業
2009年 大阪大学大学院基礎工学研究科物質創成専攻博士課程修了、博士（理学）
（大阪大学、2009年、指導教官：真島和志教授、大嶋孝志准教授）、2009年より現職。
第4回GSCポスター賞（2008）、日本化学会第88春季年会学生講演賞（2008）、
JSPC Award for Excellence 2008（2008）、有機合成若手セミナー優秀研究発表賞（2008）、
Reaxys PhD Prize 2010 ファイナリスト（2010）、
有機合成化学協会研究企画賞旭化成ファーマ研究企画賞（2011）
Reaxys Prize Club Symposium in Japan 2014.3.28
Reaxys Prize Club Symposium in Japan 2014.3.28
9
(-*0'%$&―
Carbon-Carbon Bond Formations by Anionic Group 9 Metal
Complexes
1
2#"!"
(Grad. Sch. of Eng., Osaka Univ.) Takanori IWASAKI
Reaxys Prize Club+0.,)/ in Japan 2014 @ 2014328
How to Design New Transition Metal Catalysts
• 39 transition-metal elements
• Valent of transition metal center
• Coordination number
• Neutral or cationic (anionic?)
• Ligand control
• Bimetallic, multimetallic etc…
Umpolung transition metal center, namely
anionic transition metal species are not wellestablished in contrast with other
approaches to design novel catalytic system.
Can it be an effective approach to
develop new class of catalysts? 1
Reaxys Prize Club Symposium in Japan 2014.3.28
Anionic Transition Metal Species –Gilman Reagent–
–
CuX
+
R Cu R m+
R–m
m = Li, MgX
Gilman, H. JOC 1952.
Cuprate-mediated C–C bond formations
1,4-Addition
R'
SN2' reaction
–
R Cu R
m+
R'
R
X
O
–
R Cu R m+
R
O
Cross-coupling
Carbocupration
–
R' R Cu R m+
R
–
R Cu R
m+
Alkyl–X
Alkyl–R
R'
Cu
R'
R'
Anionic Cu species (Gilman reagent) show excellent reactivity toward various
substrates, implying synthetic utility of anionic transition metal species and could
be used in catalytic manner in some cases.
Anionic Transition Metal-Catalyzed C–C Bond Formations
Br
+
R3Si
R3Si
MnCl2
Alkyl–MgCl
Alkyl
Br
R3Si
R3Si
Br
Br
Alkyl–X
Alkyl
+
R3Si
MgCl
SiR3
CoCl2
R3Si
SiR3
+
Alkyl
NiCl2 or Pd(acac)2
R–m
m = MgX, ZnX
–
Mg+Cl
Mn
Alkyl
Oshima, K. TL 1997.
SiR3
2–
R3Si
SiR3
Co
(Mg+Cl)2
R3Si
Oshima, K. ACIE 2005.
–
Alkyl–R
M
m+
R
M = Ni, Pd
Kambe, N. JACS 2002, ACIE 2004.
However, anionic transition-metal-catalyzed C–C bond formation is rarely
discussed except the case of Cu.
Herein, new entry of group 9 metals (Co and Rh) in C–C bond formations will be
presented.
2
Reaxys Prize Club Symposium in Japan 2014.3.28
This Work–Co-Catalyzed Alkyl-Alkyl Cross-Coupling Reaction–
R1
Alkyl
+
X
XMg
R2
2 mol% CoCl2
4 mol% LiI
2 eq
or
R3
R1
THF, 50 ˚C
Alkyl
R2
R3
–
R'-MgX
Co R' Mg+X
R-X
B
Co
MgX2
A
Co
R R'
R'
R
C
Iwasaki, T.; Takagawa, H.; Singh, S. P.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2013, 135, 9604.
Conditions Screening
nOct
Br +
tBu
MgCl
1.2 eq
2 mol % CoCl2
4 mol % LiI
2 equiv 1,3-butadiene
THF, 50 ˚C, 5 h
standard conditions
nOct
tBu
+ Octane + Octenes
nOct-tBu (%) Octane (%) Octenes (%)
variation from standard conditions
none
84
1
1
NiCl2 instead of CoCl2
7
1
trace
PdCl2 instead of CoCl2
trace
3
11
CuCl2 instead of CoCl2
19
trace
2
no LiI
18
trace
4
no 1,3-butadiene
trace
trace
16
at 0 ˚C
n.d.
trace
2
isoprene instead of 1,3-butadiene
92
1
trace
LiCl instead of LiI
27
2
7
CoI2 and LiCl
76
1
3
nOct
* 58% of
tBu was obtained.
Ineffective catalyst: CrCl2, MnCl2, FeCl2
entry
1
2
3
4*
5
6
7
8
9
10
Cf. Chem. Commun. 2008. Me, Ph
Ineffective additive: PPh3, TMEDA, Ph
3
Reaxys Prize Club Symposium in Japan 2014.3.28
Co-Catalyzed sp3C-sp3C Coupling
nOct
Br
nDec–Br
nBu–Br
10 mol% CoCl2(dppp)
+ ClMg
THF, –20 ˚C, 2 h
5 mol% cat.
30 mol% TMEDA
THF, rt
iPr
nPen
nBu
nOct
iPr
iPrN
PPh2
iPrN
H N
PPh2
N
Cl Zr
PPh2
PPh2
H
Co I
N
iPr
R=
98%
nDec–R
sBu
20%
THF, 10 ˚C, 1 h
tBu
0%
Cahiez, G. Adv. Synth. Catal. 2008.
nOct–MgBr
+
90%
Oshima, K. ACIE 2002; CEJ 2004.
5 mol% CoCl2
10 mol% LiI
20 mol% TMEDA
R–MgBr
+
nOct
H
N
PPh2
iPr
63%
Co I
PPh2
38%
Thomas, C. M. Eur. J. Inorg. Chem. 2011.
Scope and Limitations of Grignard Reagents
Alkyl
Br
+
R MgX
1.2 eq
2 mol % CoCl2, 4 mol % LiI
2 equiv isoprene
THF, 50 °C, 5 h
Alkyl
R
OMe
nNon
91%
nNon
nNon
85% (82%)
nOct
nOct
81% (80%)
nOct
nNon
nOct
<1%
nOct
93%
80% (0.1 mol% CoCl2)
nOct
92%
82% (80%)
89% (83%)
nOct
77%
4%
Me
90% (86%)
nOct
Ph
<1%
*GC yield (Isolation yield)
4
Reaxys Prize Club Symposium in Japan 2014.3.28
Relative Reactivity of Alkyl Halides
R1
nOct–X
+
2 mol % CoCl2, 4 mol % LiI
2 equiv isoprene
R2
R3
ClMg
X=
relative reactivity:
1
0.3 <0.06
a
94%
62%
2%
71%
58%
I > OTs > Br > F >> Cl
>6
X
Br
Fa
Cl
I
OTs
R2
R3
nOct
THF, 50 °C, 5 h
1.2 eq
H3C
R1
–
Reaction time was 24 h
Bond Energy
X = F : 470 kJ/mol
Cl : 351 kJ/mol
Br : 293 kJ/mol
Scope and Limitations of Alkyl Halides
R1
Alkyl–Br
+
2 mol % CoCl2, 4 mol % LiI
2 equiv isoprene
R2
R3
ClMg
1.2 eq
R1
R3
Alkyl
THF, 50 °C, 5 h
R2
TBSO
CF3
95%
86%
88% (86%)
S
N
OTHP
84% (80%)
O
Et2N
80% (78%)
O
79% (73%)
O
O
81% (76%)
TsN
BocN
I
69% (67%)
95% (91%)
N
BocN
61% (60%)
80% (76%)
O
76% (74%)
78% (72%)
TsN
58% (55%)
5
EtO
79% (74%)
* GC yield (Isolation yield)
Reaxys Prize Club Symposium in Japan 2014.3.28
Selective Cross-Coupling
Cl
Br
Cl
Br
92%
2 mol % CoCl2, 4 mol % LiI
2 equiv isoprene
Br
Br
THF, 50 °C, 5-12 h
R1
Br
86%
R2
R3
ClMg
1.2 eq
Br
Br
94%
Investigation on Reaction Mechanism
2 mol % CoCl2
4 mol % LiI
2 equiv isoprene
Br + R
1.2 eq
R
R +
MgCl
THF, 50 °C
12 h
RMgCl
1˚ (nOct)
71%
2˚ (3-Hep)
68%
3˚ (2,5-Me-2-Hex) 50%
3%
<1%
2%
D Ha
tBu
D Ha
Br
tBu
D Hb
threo
+
tBu–MgCl
2 mol % CoCl2
4 mol % LiI
2 equiv isoprene
THF, 50 °C, 5 h
73% yield
tBu
>95
erythro (inversion)
Ja-b = 12.4 Hz
+
D Ha
tBu
tBu
6
Hb D
D Hb
threo (retention)
Ja-b = 6.9 Hz
5
Reaxys Prize Club Symposium in Japan 2014.3.28
Time-Course of Dimerization of Butadiene
nNon–Br
CoCl2
LiI
+
0.1 mmol
+
nOct–MgCl
0.4 mmol
0.2 mmol
10 mmol
THF, 50 °C
10 min
3.0 mmol
or
sBu–MgCl
3.0 mmol
Yield of dimer (%) (based on Co)
Addition of nNonBr
Addition of sBuMgCl
Time (min)
Proposed Catalytic Active Species
CoCl2
hydride source
3
–
R'-MgX
Co
Co R'
Co
Mg+X
A
B
Alkyl–Br
2
Natta, G. Chem. Commun. 1967.
Hofmann, P. Angew. Chem. Int. Ed. 2008.
7
Reaxys Prize Club Symposium in Japan 2014.3.28
A Possible Mechanism
–
CoCl2
R'-MgX
R(CH2)2MgX
Co R'
1/2 R(CH2)2H
Mg+X
2
1/2 R
B
CoCl
R-X
Co
R(CH2)2MgX
MgX2
A
R
Co
3
Co–H
R R'
R'
R
C
Organorhodium
L
Rh Ar
L
L
L
Rh
Organorhodium-catalyzed C–C bond formations
L
1,4-Addition reaction
"Ar–Rh"
EWG
Ar
• Nucleophilic Ar group
• Chiral induction
H
Ar–R
Ar
1,2-Addition reaction
O
"Ar–Rh"
or
Ar Y
Y
Heck reaction
RhI
Y
RhI–Ar
R–X
ox. add.
"Ar–Rh"
insertion
"Ar–Rh"
H
Ar
R
O
Ar
etc...
Fagnou, K. Lautens, M. Chem. Rev. 2003.
O
8
Ar
R
R
Coupling reaction
O
O
"Ar–Rh"
Y
R'
Ar'
Hydroarylation
R
Ar
OH
RAr
R'
Ar'
m–X
R
R
Ar
H–X
RhI–X
Ar–m
X RhIII
EWG
Ar
Reaxys Prize Club Symposium in Japan 2014.3.28
Anionic Diarylrhodium–Organorhodate
L
Rh Ar
L
L
L
ArMgX
L
Rh
L
L
Ar
–
Rh
Lewis acidic
Ar
Ar Mg+X
More nucleophilic
R1
Alkyl
X
+
XMg
R2
2 mol% CoCl2
4 mol% LiI
2 eq
or
R3
R1
THF, 50 ˚C
R2
Alkyl
R3
–
R'-MgX
Co
Co R' Mg+X
R-X
–MgX2
Co
R'
R
J. Am. Chem. Soc. 2013, 135, 9604.
This Work–Rh-Catalyzed Cross-Coupling via C–O Bond Cleavage–
cat. [RhCl(cod)]2
OR + Ar–m
R'
Ar
R'
THF, rt
R = Ph, OAc, SiR3
m = MgX, ZnX
OR
O
O
O
O
R–m
R–m
O
O
S
O
O
cat. M
conventional methods
R cat. M
CF3
CH3
O
O
O
R
P
N
OR
O
R
O
OR
O
S
N
O
N
R
O
R
R
N N
S
This work
O
O
O
O
S
O
N
O
Hal
O
O
R
m
O
Ph
R
SiR3
m = alkali metal
Anionic Rhodium-Catalyzed Cross-Coupling Reaction will also be presented.
9