金属への酸化的付加とC-M結合形成
反応のパターン
X

X

X

R X

R
allyl

aryl

alkenylalkyl

求核置換型の酸化的付加
X

M

M

R M X

X

M
X

R

R M
X

三中心遷移状態を経由する酸化的付加

X
M
π-complex

R X

M

M
X

2021年度
有機金属化学第9回

M X

X

M

M

X
M

X
π-allyl

π-complex

R M
X

X

M
X

M

反応例

反応例
Cl

Pd(0)
PdCl2 + ROH

Cl

Pd
Pd

Cl

Pd(PPh3)4–2PPh3“Pd(PPh3)2”

Ph Br

Ph
PPh3 Pd PPh3
Br辻・Trostアリル化
最初の報告

Cl

Pd
Pd

O

Pdは触媒量でも良い：Tsuji-Trost allylic alkylation

O

EtO

O

OEt

O

EtO

Cl

R

OEt

X+

1526

Pd(0) cat.
Nu

R

Nu
+

R
Nu

π-allyl配位子は求核攻撃を受ける

Nu

Experiments
were
the
反応機構
R
R’ carried out to determineR
R’ course of nuc

Pd(0) +

Pdi.e., t o s o l v e the question of the relative rates of nucleophilic

Pd
NuX
merit z-ally1 complexes
4x and 4n8. Unfortunately,interconveNu

at least 50 times faster than nucleophilic attack so that no ded

Tsuji, J.; Takahashi, H.; Morikawa, M.
Tetrahedron Lett. 1965, 6, 4387-4388.

preparative
experiments
and theRNMR work,
R
R’
R’ i.e., particular im
opening of the Pd-C3 bond, Le., the bond trans to P, upon
Pd Nu
Pd X
that attack frans to the Pd-P bond is easfec than drans to the

Trost, B. M.; Fullerton, T. J.
J. Am. Chem. Soc. 1973, 95, 292-294.

tion of the predominant reactionproductit f d k w s t h a t t h e 8 x
inversion
inversionRR’ beformer. The same’conclusioncandrawn by applying Bos
Nustate of nucleophilic attack
Pdresembles the kaltyl intermediate;
omer, here 4x, that gives theXmajor enantiomeric product; if s

不斉反応(非対称化)

Cl
OAc
R

+
O

MeO

R

Pd
Pd

O
Cl

Ph2P

O

N
tBu

1 mol%

2.5 mol%

MeO
R

O
OMe

２回の求核置換を経由して反応※

cur trans to the Pd-P bond in order to give rise to the observed

O

The s

OMe

deriveR

R = Me, 50% yield, 97% ee
R = iPr, 96% yield, 88% ee
R = Ph, 99% yield, 99% ee

Matt, P. v.; Pfaltz, A., Angew. Chem. Int. Ed. Engl. 1993, 32, 566-568.

azoline

WL... 4tyπアリル中間体においてtype
ホスフィンのトランスが少し長い
naphth→ferentNu

Sprinz, J.; Kiefer, M.; Helmchen, G.; Reggelin, M.; Huttner, G.; Walter, O.; Zsolnai, L., Tetrahedron Lett. 1994, 35, 1523-1526.
Re f e r e n c e s and N o t e s

PhCl
PhCl
Dichlorobenzene

EtMgBrn-BuMgBr
n-BuMgBr

クロスカップリング：反応形式と発見まで

A

mトランスメタル化の発見
Pn-C8H1,MgC1
CH-CHCl
Et3PhMgBrP
Br (o-tol)MgBr EtCHz=CHCl’
Br
3P
PhMgBr
ClCH=CHClf
Ni
Ni

A

0-

反応形式
Ar X + M R

Pd cat.

Ar R反応の重要性：

Et3P

Et3cisP

Br

trans-Br

PhMgBr
CIzC=CHz’
Chatt,
J.; Shaw, B. L., J. Chem.
Soc. 1960, 1718-1729.
a-NpMgBrh
CH-CHCI

一般的反応機構

A
A
B
B
A0
A
AQ
B

酸化的付加・還元的脱離の存在は示唆されていた= The experimental conditions are not necessarily optimum. Grignard reagent

LnPd(0)
Ar R

A

Ar X

Conditio
halide = 10-2-10-3; solvent is diethyl ether, unless otherwise noted.
in the text (example l), and condition B for a-vinylnaphthalene (example 2). C
Et unless otherwise noted.
NPh
e Yields based on glpc analysis using anlatedN yields,
Ph Cl+ n-butane
0 In order
was refluxed for 20 hr. * Np =Ni to ensure the reaction, theNi mixture
benzene,N and
Et tetrahydrofuran ( 2 :3N:1). Cl

and theresults
LnPd
LnPd
chloro[RX
C12(dpUchino, M.; Yamamoto, A.; Ikeda, S.
NJ.
Organomet.
Chem.
1970,
24,
C63-C64.
given
f
/Et
/ph
(dipy)Ni+ PhCl +(dipy)Ni ‘0.5PhCl + Et-Et (1) butylbe\
Exam
M X M R
Et
\Cl
クロスカップリングの発見
0.39 mhalogen-nickel bondreadily reacts with a Grignard reand 50(dppe)NiCl2反応の分類 M-R反応剤の金属により名前が異なる
agent to form the corresponding
bromid
0.7 mol% organonickel bond. l 3
suggest a catalytic
EtMgBr
Et of a dihalodiPhThese
Phability
Cl +facts
ring ov
熊田・玉尾・Corriuカップリング 根岸カップリング
phosphinenickel for the coupling98%
of a Grignard reagent
heatedM = MgX, Li; cat: Pd or Ni
M = ZnX; cat: Pd or Ni
withanorganic
halide.
hydroly
反応機構も同時に提唱
layer aStilleカップリング
檜山カップリング
LzNiXz + 2RMgX’ +LzNiRz + 2MgXX’(2)
combin1
M = SnR3; cat: Pd
M = SiR3 (+ base); cat: Pdride, an
L2NiR2 + R‘X” -+ L2Ni(R’)(X’’) + R-R( 3)
鈴木・宮浦カップリング
園頭・萩原カップリング
tilled u2(9.63 g
M = BX2 (+ base); cat: Pd
M = Cu (with alkyne); cat: Pd
Tamao,
K.;
Sumitani,
K.;
Kumada,M.
di-n-bu
RMgX’
MgX’X”
J.
Am.
Chem.
Soc.
1972,
94,
4374-4376.
bp 75-7
/XI’
\ f
Ar

Ar

the complex itself is converted to the corresponding(halo)(organo)nickel
complex, 11, l 2 as exemplified by eq
N
1. l 1 The second Ni(0)is the well-established fact that such a.

熊田・玉尾カップリング
二座配位子の効果
Ph Cl + nBuMgBr

ハロゲン化アリールによる違い(L)NiCl2
0.7 mol%

Ph2P
PPh2 Ph2P
PPh2 Ph2P
PPh2
dppe
dppp
dppb
Me2P
PMe2
dmpe

PMe2
Fe
PMe2

dmpf

Ph X + nBuMgBr

Ph nBu(dppp)NiCl2
0.7 mol%

X
F
Cl
Br
I

L
yield (%)
dppp
100
94
dmpf
2PPh3 84
79
dppe
47
dmpe
28
dppb
6
2Et3P

Ph nBuyield (%)
31
95
54
80

Kohei, T.; Koji, S.; Yoshihisa, K.; Michio, Z.; Akira, F.; Shun-ichi, K.; Isao, N.; Akio, M.; Makoto, K., Bull. Chem. Soc. Jpn. 1976, 49, 1958-1969.

トランスメタル化における異性化＝選択性低下→Pdなら解決
Ph+ PhMgBr
Brtrans:cis = 92:8
Br
+ PhMgBrtrans:cis = 5:95
Ph

MgBr
+ PhBrtrans:cis = 29:71
Ph(dppp)NiCl2
Ph
1 mol%

+

Ph

Ph

Ph
93:7
88% yield(dppp)NiCl2
Ph
1 mol%(dppp)NiCl2
Ph
1 mol%

アルケニルMgを使うと異性化
→

+

Ph

Ph

Ph
7:93
100% yield
+

Ph

Br
+ MeLitrans:cis = >99:1
Ph

nHex

+

BrMg

Pd(PPh3)4
3 mol%

Ph

+

Ph

Ph

Ph
1:>99
88% yield
Pd(PPh3)4
3 mol%nHex

I
97% isomeric purity
87% yield
Ph

Pd触媒を用いると立体を完全に制御可能

Ph
99:1
42% yield

Tamao, K.; Zembayashi, M.; Kiso, Y.; Kumada, M., J. Organomet. Chem. 1973, 55, c91-c94.
Zembayashi, M.; Tamao, K.; Kumada, M., Tetrahedron Lett. 1975, 16, 1719-1722.

根岸カップリング
有機Alの利用

Pd(PPh3)2Cl2
5 mol%
HAliBu2
10 mol%

I

nPent

+

Alの反応性が高すぎて
酸素官能基すら厳しい
nPent

nBu

AliBu2nBu>99% isomeric purity
74% yield

nPent+ HAliBu2

Baba, S.; Negishi, E., J. Am. Chem. Soc. 1976, 98, 6729-6731.

有機Zrの利用で官能基許容性向上
Br

O

+

O

O

OCH3

ZrCp2ClEi-ichi Negishi
Nobel Prize 2010

Pd(PPh3)2Cl2
5 mol%
HAliBu2O
10 mol%

複雑天然物の合成にも応用された

O
70% yield

R+ Cp2Zr(H)ClOCH3
O

Okukado, N.; Van Horn, D. E.; Klima, W. L.; Negishi, E.-i.
Tetrahedron Lett. 1978, 19, 1027-1030.

IO

有機亜鉛の利用で官能基許容性向上
O
ZnCl + Br

O
70%

OCH3

Negishi, E.; King, A. O.; Okukado, N., J. Org. Chem. 1977, 42, 1821-1823.
King, A. O.; Okukado, N.; Negishi, E.-i.
J. Chem. Soc., Chem. Commun. 1977, 683-684.

試薬そのものが作りやすい

OTBS

PMP

+ ZnCl2

OPMB
I

O

O

OTBS

OTBS

PMP
66%
OPMB

Ni(acac)2 (5 mol%)
PPh3 (5 mol%)
HAliBu2 (5 mol%)

OCH3

O

1) tBuLi
2) Pd(PPh3)4 (5 mol%)
OTBS

O

O

OH

OH

13 steps
NH2(+)-Discodermolide
HO
OO

Smith, A. B.; Beauchamp, T. J.; LaMarche, M. J.;
Kaufman, M. D.; Qiu, Y.; Arimoto, H.; Jones, D. R.; Kobayashi, K.
J. Am. Chem. Soc. 2000, 122, 8654-8664.

~~

~~

Stilleカップリング
Br + Me4Sn

BnPdCl(PPh3)2
0.7 mol%
O=P(NMe2)3

89%
Milstein, D.; Stille, J. K., J. Am. Chem. Soc. 1979, 101, 4992-4998.

驚異の安定性(a)(b)
nBu Sn
3

1

O
EtO P
EtO

CO2Et

3
(a) (nBu3Sn)Cu(nBu)Li·LiCN(b) SO3·py, NEt3

1) nBuLi, DMPU
2) 3
73%

CO2Et

nBu Sn3

古い文献にはPd(dba)2と記載されることあり＝本当はPd2(dba)3·dbaである
実験化学講座にも合成法記載
ただし市販品にはPdナノ粒子が含まれる→触媒反応の再現性低下の原因
不斉反応ではeeが下がることも多い
CHCl3で共結晶化するときれいなPd2(dba)3·CHCl3になる~~~

Zalesskiy, S. S.; Ananikov, V. P.
Organometallics 2012, 31, 2302-2309.

日本語での解説
http://chemistry4410.seesaa.net/article/261041452.html
0276-7333/90/2309-307$02.50/0

Ar

Domínguez, B.; Iglesias, B.; de Lera, A. R.
Tetrahedron 1999, 55, 15071-15098.

配位子の効果H H
Pd C SnR3
R’
L
open-SE2

高極性溶媒・配位性溶媒
relativeligandrate
PPh3
1
P(o-tol)335
P(2-furyl)3 105
AsPh3
1100
SbPh3
13

R R

X

6

立体効果というよりは電子効果

He won numerous awards, including the William H.
Rauscher Memorial Lecturer (1974). the Gossett Lecturer(19i9), the Case Centennial Scholar (1980), the ACS Awardin Pol.ymer Chemistry (1982), the 1989 American Chemical
Society Colorado Section Award, and the Arthur C. Cope
Scholars Award (1989).
He served on the Advisory Board of Jnurnal of Polymw
Science, the Editorial Boards of Advances in Polymer
Science and Macromolecular Syntheses, and the Advisory
Board o f Journal of Molecular Srience and served as an
Associate Editor for Macromolecules between 196i and1981. Professor Stille was an Associate Editor for the
Journal of the American Chemical Society from 1982
through 1986 and was on the Advisory Board of Organometallics. He served as a frequent advisor to NASA.
He authored over 270 publications, wrote two books. andcontributed chapters to several books.
He is survived by his wife Dolores and two sons, John
Robert and James Kenneth. John Rohert, 31, is a faculty

0 1990 American Chemical Society

トランスメタル化の詳細反応機構

CO2Et

Pd2(dba)3
2 mol%
ligand8 mol%
THF, 50 °C

John K. Stille(died 1989)

Professor John K. Stille was horn May 8, 1930, in
Tucson, Arizona. He received his bachelor's degree in 1 9 3
and master's degree in 1953, both from the Llniversitv of
Arizona. He received his Ph.D. in 1957 from the University
of Illinois under the supervision of the late Professor
Marvel. In 1957, he joined the faculty a t the Universityof Iowa and became Professor in 1965. In 1977, Professor
Stille joined the faculty at Colorado State University. In
1986 he was appoined University Distinguished Professor,
one of seven such appointments a t Colorado State. Professor Stille had been a Visiting Professor at the RoyalInstitute in Stockholm (1969) and the University of Calilornia at Santa Cruz (1980).
During his career, he directed 94 Ph.D. students and 97
postdoctoral fellows. He consulted for E. I. du Pont deNemours & Co., Textile Fihers Department, since 1964 andwas also a consultant for Syntex (USA) Inc.

5

OTf Pd2(dba)3 (2.5 mol%)
AsPh3 (20 mol%)62%

酸化・塩基条件にも耐える

I + nBu Sn
3~~~John K. Stille

Biographical Sketch

CHO

OH 96% nBu3Sn
2

4

~~

おまけ：Pd2(dba)3

最初の報告

OH

~~

:c Copyright 1990
American Chemical Society

Volume 9 , Number 12,December 1990

cone
angle
145
194
N/A
142
142

Farina, V.; Krishnan, B., J. Am. Chem. Soc. 1991, 113, 9585-9595.

X
L

Sn R
H
C
H
R’

R R
X

Sn R
H
C
H
R’

L
Pd
L
Ar
Ar
cyclic-SE2
cyclic-SE25-coordinate Pd
低極性溶媒
Pd

溶媒により異なる
Labadie, J. W.; Stille, J. K., J. Am. Chem. Soc. 1983, 105, 669-670.
Labadie, J. W.; Stille, J. K., J. Am. Chem. Soc. 1983, 105, 6129-6137.
Casado, A. L.; Espinet, P., J. Am. Chem. Soc. 1998, 120, 8978-8985.
Casado, A. L.; Espinet, P.; Gallego, A. M.
J. Am. Chem. Soc. 2000, 122, 11771-11782.

檜山カップリング
高配位silicateからのトランスメタル化
PdCl2 Ph2–

K+2 Ph

SiF5

54%

Ph

Ph

PdCl

Yoshida, J.; Tamao, K.; Yamamoto, H.; Kakui, T.; Uchida, T.; Kumada, M.
Organometallics 1982, 1, 542-549.

最初の報告
+
I

Ph

Ph

I

Me3Si

+ Me3Si+ TASF[(allyl)PdCl]2
2.5 mol%

NEt2
Et2N S NEt2

O=P(NMe2)3[(allyl)PdCl]2
2.5 mol%
P(OEt)3
5 mol%Ph+ TASF
THF
OH+ Me3Si+ TASF

TASF
tris(diethylamino)sulfonium
difluorotrimethylsilicate

98%

Tamejiro Hiyama

トランスメタル化の詳細

F
Si
F

SiF3

TfO
+

驚異の官能基許容性
無保護ヒドロキシ基
を利用可能
76%

[Pd(PPh3)4]
5 mol%
nBu N+F–
4
1 equiv.
THF

1194

J . Am. Chem. SOC.1
O

O
*" I

I

温度による立体特異性の逆転→[(allyl)PdCl]2 Ph
2.5 mol%
THF

Br

84%

OH

Hatanaka, Y.; Hiyama, T., J. Org. Chem. 1988, 53, 918-920.
COOEt
SiF3

TfO
+

+ TASF

COOEt

Pd(OAc)2
5 mol%
THF

98%

( R40
)
Hatanaka, Y.; Hiyama, T.
40
J. Am. Chem. Soc. 1990, 112, 7793-7794.

アリルγ位でも反応
二置換γ位でも反応
Hatanaka, Y.; Ebina, Y.; Hiyama, T., J. Am. Chem. Soc. 1991, 113, 7075-7076.

TfO Me HAr

Pd
L

C SiF4p-tol

open-SE2
inversion

50

60

80

70

90

100

110

temperature ("C)

Figure 1. Temperature
Me H dependence of the stereochemistry of the crosscoupling products 3a and 3b derived from l a (34% ee).
TfO
SiF4

C

p-tol
TfO

SiF4

L

Pd

PdLn

Ar
open-SE2

Ar

H
C
Me
p-tol

cyclic-SE2

sE2kyCiic)

SE2(open) Ret

S ~ 2 ( o p e nInv
)

U

U

U

retention

retention

鈴木・宮浦カップリング
最初の報告
nBu

B
O

[Pd(PPh3)4]
1 mol%NaOEt
2 equiv.

+ Br

O

Ph

nBu

THF

Ph

80%

Miyaura, N.; Suzuki, A., J. Chem. Soc., Chem. Commun. 1979, 866-867.
Miyaura, N.; Yamada, K.; Suzuki, A., Tetrahedron Lett. 1979, 3437-3440.

複雑天然物や市販薬の合成への応用
Cl

H 2N

NH

HN

Akira Suzuki
Nobel Prize 2010

N

H

Br

HO

N
H

O

Norio Miyaura

NH
H
N

O

HN
dragamacidin F

NOClBoscalid®

多置換のビアリール合成に非常に強力な手法となる

K. Eicken, H. Rang, A. Harreus, N. Götz, E. Ammermann, G. Lorentz,
S. Strathmann, German Patent DE19531813, 1997.
K. Eicken, M. Rack, F. Wetterich, E. Ammermann, G. Lorentz,
S. Strathmann, German Patent DE19735224, 1999.
Garg, N. K.; Caspi, D. D.; Stoltz, B. M., J. Am. Chem. Soc. 2004, 126, 9552-9553.

液晶分子の合成への応用
F

F

C5H11

F

B(OH)2Pd(PPh3)4, Na2CO3

F
+ Br

C5H11

C5H11

C5H11
F F

C5H11

F

F
C5H11

F
C5H11

F F

C5H11

F
C5H11

F F

F
C5H11

C5H11

原料のボロン酸とハロゲン化アリールを選べば位置異性体を作り分けることが可能
→

C5H11

M. E. Glendenning, J. W. Goodby, M. Hird and K. J. Toyne
J. Chem. Soc., Parkin Trans. 2, 2000, 27-34.

鈴木・宮浦カップリング：トランスメタル化の機構
二種の反応機構の提案
nHex

B

nHex

HO–

OH
B

二種の反応の速度差の観測
L2Pd(R)X
H
O
BR2
L2RPd
nHex

nHex

HO
B O

nHex

B O

L2Pd(R)XHO–
L2Pd(R)OH
H
O

HO–

L2RPd

R

nHex

R

nHex

Br

Pd

(HO)3B

PPh3

二種の反応機構が提案
A: 塩基がBと錯形成
B: 塩基がPdと錯形成

R

OH

OH

PPh3

R
L2RPd

k = 1.1 × 10–6
[M–1·s–1]

PPh3

R

R

nHex

R

nHex

Pd OH
PPh3

BR2
L2RPd
nHex

FULL PAPER

Matos, K.; Soderquist, J. A., J. Org. Chem. 1998, 63, 461-470.

反応速度の塩基濃度依存性

k = 1.6 × 10–2
[M–1·s–1](HO)2B

Carrow, B. P.; Hartwig, J. F., J. Am. Chem. Soc. 2011, 133, 2116-2119.

修正触媒サイクル
LnPd(0)ArPdCl(PPh3)2とPhB(OH)2の反応

Ar R

Ar X
Ar

Ar

LnPd

LnPd
R

B(OH)3
RB(OH)2 LnPd

Amatore, C.; Jutand, A.; Le Duc, G., Chem. Eur. J. 2011, 17, 2492-2503.
Amatore, C.; Le Duc, G.; Jutand, A., Chem. Eur. J. 2013, 19, 10082-10093.

X
OH

Ar
X
OH

トランスメタル化前にハロゲンが塩基と置き換わる
F–による活性化も同様に進行

coupling is commonly proposed to involve 14-electron, threePublished on Web 07/17/2002
coordinate complexes.7-9 Three-coordinate, 14-electron palladium(II) complexes have not been isolated, but are believed to be favored
Figure 1. X-ray structure of 1 is shown on the left, and 3b is shown on
Synthesis,
Characterization,
andReactivity of Monomeric, Arylpalladium
10-13
the right.
when the catalysts possess stericallyhinderedligands.
Three最初の報告(東ソー)：C-N
bond
formation
Complexes
with[Rha Hindered Phosphine as the Only Dative Ligand-14 and rhodium
coordinate 14-electron Pd(OAc)
nickelHalide[Ni(mes)3]
かさ高い配位子を有するAr-Pd中間体
2 0.02 mol%
‡ Michael§ and John F. Hartwig*,‡
Scheme Bühl,
1
MeO
MeO
tBu 0.08 mol%
+15
James
P.
Stambuli,P3(PPh3)]
complexes havet been isolated, but these unsaturated
NaO Bu 1.4 equiv.
of Chemistry,
Yale UniVersity,
P.O. Box 208107, New HaVen, Connecticut 06520-8107, andBr +not
H N
N H
N We
N Hreport
species areintermediates
inDepartment
catalytic chemistry.
the
120 °C, 4 h
Max-Planck-Institutfür Kohlenforschung,94%
isolation of a series of monomeric
arylpalladium(II)halide com- Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany
Pd(OAc)2 0.025 mol%
Received April 5, 2002
plexes with a single dative
ligand.
PtBu3 0.1
mol% These complexes are likely
従来反応しにくかった
NaOtBu 1.2 equiv.
intermediates
in metal-catalyzed
cross-coupling
reactions.
N
Cl + H N
塩化アリールでも反応
Most organometallic
reactionsthroughintermediates
that
130 °C, 5 h
HThe monophosphine,
arylpalladium
halideoccur
complexes
werepossessinanScheme
open coordinationsite.1 Such of
unsaturated
structure was obtained (Figure 1). Complex 1 is a T-shapedsynthesized as shown
1. The combination
Pd(dba)2intermediates
,
>99%
byY.,
kinetic
studies Lett.
and arerarelyobserved
Nishiyama,
M.;generally
Yamamoto,
T.; Koie,
Tetrahedron
1998,
39, 617-620.
monomer. The phenyl group is located trans to the open coordinaphosphine,
and arearyl
halide indetected
THF
solvent
formedarylpalladium
2,3
directlyorisolated.
For
example,oxidative
additionandreductive
Yamamoto,T.; Nishiyama,M.; Koie,
TetrahedronLett.
1998, 39, 2367-2370.
tion site of the metal. This geometry allows the ligand with thehalidecomplexes
1-3b, as shownin Y.,
Scheme1.16 The
monophoselimination4,5 are often preceded by dissociation of a dative ligand,greatest steric demand to bind in the least hindered position andphine-ligated arylpalladium
halides were also prepared by dissoluビフェニル系配位子の発見
and migratory insertion requires an open coordination site forthe covalent ligand with the largest trans effect23 to bind trans totion of Pd(dba)2binding
and thePdof
appropriate
ligandneatarylpalladium-catalyzed
halide. The2(dba)3 0.5 mol%
6 As inasubstrate.
aresult,cross
L1 1.5 mol%theopen site. The angles about theX線結晶構造解析にて
palladium are 100.9°, 91.3°,
products were isolatedbyprecipitation
from
THF
after
concentrationt
1.4 equiv.
couplingNaOisBucommonly
proposed to involve 14-electron,
threePCy2N
MeO
Cl + H N
MeO
３配位構造を確認
and 162.6°. Hydrogens H17 and H18
were refined isotropically,
7-9of the reaction
solutionor complexes.
fromaryl halide
by additionof palladium80 °C the neatcoordinate
Three-coordinate,14-electron
95% 17 accompanied
and the distance between the palladium and the closest hydrogenpentane. Formation
dimeric
Pd(I)halides[LPdX]
Pd(OAc)2but are believed to be favored(II) ofcomplexes
havenotbeen isolated,
2 2 mol%
Figure 1. X-rayStambuli,
structure ofshownM.;
on Hartwig,
the left, and3b is shJ. 1P.;isthe
Bühl,
J.agosticF.
L1 3 mol%(H18)
is2.27(3)Å,whichiswithindistance
of
an
10-13
L1
the generation ofwhen
the oxidative
addition
product,buttheformationMeN
theright.
the catalysts
possess sterically hindered ligands.
Three2
CsF 3 equiv.
Am. Chem. Soc. 2002, 124, 9346-9347.
24 CrystalsJ.of-14
MeO
Cl + (HO)B
MeO
interaction.
P(t-Bu)3-ligated 2-m-xylyl complex 3b
2of this dimericmaterialwas
suppressedbyconducting
reactionscoordinate 14-electron
nickel[Ni(mes)]andrhodium[Rh3
RT
Scheme1
were suitable for X-ray diffraction (Figure 1). Again, the geometry92%(PPh3of)]+15
complexes
have0.1been
isolated,
but thesewith concentrations
palladium
below
M in
THF solvent
or unsaturated
wasare halide.
not intermediates
catalytic
WereporttheT-shaped. The angles about palladium were 100.9°, 94.0°, andOld,
D. W.;J.
P.; aryl
Buchwald,
S. L., J. Am.in
Chem.
Soc.chemistry.
1998, 120,9722-9723.
below
0.5Wolfe,
M in speciesneatisolationa seriesof monomeric
arylpalladium(II)com- The calculated distance between the metal and H27 boundThese
complexes
wereofalso
obtainedby direct oxidative
addition halide 164.6°.
tBu
3Pを用いる鈴木・宮浦カップリング tBu3Pは鈴木・宮浦カップリングや
18 Additiona precursors.
single dative
ligand. These
to C16 was 2.33 Å, which could, again, reflect an agostic reaction.
of aryl halides toplexes
the L2withPd(0)of 40 complexes
equiv of are likely
Pd2(dba)
3 1.5 mol%
Stilleカップリングに対しても有効
31P and 13C NMR spectroscopy suggested that similar structuresintermediates
metal-catalyzed
cross-coupling reactions.
PtBuin3 3.6 mol%
PhBr to Pd[P(t-Bu)
2(1-adamantyl)]
2 formed 1 in 50% yield. AddiCsCO2
equiv.
2
3
The monophosphine,
arylpalladium
complexes were
were present in solution. The unusual91000000
19
TON!!
coordination
number was
Cl + (HO)oftion of 40 equiv
formed 3a inhalide
50% yield
2B PhI to Pd[P(t-Bu)3]2
Pd(OAc)2 0.000001 mol%
80
°C,
5
h
(100
°C,
24
h)
structurewas
obtained(Figure1).
Complexis a Tsynthesized as shown in Scheme 1. The combination of Pd(dba),
L1 0.000002
mol%2
indicatedby an upfield,
ratherthan downfield, change in 1chemical
along with 36% of the Pd(I) dimer. Reaction of Pd[P(t-Bu)
86%3]2 withOKPO2equiv.
3 The
4monomer.
phenyl group is located trans to the open co
mol% in THF solvent formed arylpalladium
phosphine, Pdandaryl
2(dba)
3 1.5halideshift
Br +upon(HO)2Boxidative addition to the L2Pd
MeOcomplex. Typical arylpal40 equiv of PhBr formed smallof the oxidative addition
PtBu3 6 amounts
mol%
16 The monophosRT
tion
site
of
the
metal.
This
geometry allows the ligand w
halide complexes
1-3b,
as
shown
in
Scheme1.
31
CsF 2.2 equiv.
ladiumhalidecomplexes
displayP
NMR
chemical
shifts that are
tBu
product
after
12
h,
but
many
side
products
wereformedatlonger91%n
P
MeO
Cl + Buphine-ligated
MeO
2
greatest
stericdemand
to
bind
in
the
least
hindered
positi3Snarylpalladium
halideswere
also
preparedbydissolu21 A cis
80 °C, 5 hlocated downfieldofthecorresponding
Pd(0)complex.
23
reaction times. These
resultsareconsistent
withreductive
eliminathe covalent ligand with the largest trans effect to bind t
94%tion of Pd(dba)2 and the appropriate ligand
in neat aryl halide. The
dispositionof arylgroups was shown by a smalltion of aryl bromides
ortho-substitutedaryl
theopenandsite.phosphine
The
Littke,A. F.;andFu, chlorides
G. C., Angew.
Chem.
Int.
Ed.THF
1998,
37,concentration
3387-3388.
products
wereisolatedby andprecipitation
from
after
L1 angles about the palladium are 100.9°,
20
JP-Coffor theandipso
carbon.
iodides reported
additionsto1999,isolated
162.6°.
Hydrogens H17 and H18 were refined isotro
Littke,A.reactionF.; Fu,TheseG.
C., oxidative
Angew.
Chem.
Int. Ed.
ofrecently.
thesolutionor fromthe neataryl
halide38,
by2411-2413.
addition
Infrared andspectroscopy
complexes
1 and 3 andin KBr
did not
17
L2Pd complexes
weresloweradditionsto the1:1 mixtureof 4020-4028.
the distanceofbetween
the palladiumthe closesthyFormation
dimeric
halides[LPdX]122,
Littke, A.pentane.
F.; Dai,C.; Fu,than
G. of
C.,
J. Am. Pd(I)
Chem.
Soc.
2000,
2 accompanied
provide evidence for agostic interactions. However, infrared spectra

鈴木・宮浦カップリング：かさ高い配位子の加速効果

園頭・萩原カップリング
最初の報告
Br
+ H

Ph

Pd(PPh3)2Cl2 5 mol%CuI 10 mol%
Et2NH (solvent)RT, 3 hPh

90% yield
100% regioselective

Sonogashira, K.; Tohda, Y.; Hagihara, N., Tetrahedron Lett. 1975, 16, 4467-4470.

反応機構
Ar

LnPd(0)Ph

S y n th e s is Ar
of X
th e C1ʹ-C11ʹ
Ox a zo le -Co n ta in in g S id e Ch a in o f
Le u c a s c a n d ro lid e A. Ap p lic a tio n o f a
Ar
Ar Cro s s -Co u p lin g
S o n o g a s h ira

LnPd

官能基許容性を活かして
S CHEME 1. Re tro s y n th e s is o f Le u c a s c a n d ro lid e A
カルバメート存在下でカップリング
Kenkichi Sonogashira

LnPd

Les A. Da kin , Neil F . XLa n gille, a n d J a m es S. P a n ek*,†Ph
Departmen t of Ch em istry an d Cen ter for S tream lin ed
S yn th esis, M etcalf Cen ter for S cien ce an d E n gin eerin g,
B oston Un iversity, 590 Com m on w ealth Aven u e,
B oston , MPhassach u setts 02215
Cu X
Cu

H

Ph
+ R 3Npan ek @ch em .bu .ed u
R3NH+X–
R eceived J u n e 12, 2002

金属とアミンと末端アルキンを混合すると脱プロトン化して
Abs tra c t: An efficien t , con ver gen t syn t h esis of t h e
C1ʹ-C11ʹ side ch a in (3) of leu ca sca n dr olide A (1) h a s been
a chJ.
ieved.
Th e key bon dChem.
con n ect ion
is m a det h r ou
gh t h e u se
Sonogashira, K.,
Organomet.
2002,
653,
46-49.
of a pa lla diu m (0)-ca t a lyzed Son oga sh ir a cr oss-cou plin g bet ween t r ifloyl oxa zole (4) a n d a lkyn ylm et a l species (5).

超分子化学では骨格をつなぐのに多用される.
Angewandte
Communications
International Edition: DOI: 10.1002/anie.201502735
German Edition:
DOI: 10.1002/ange.201502735

Porphyrin Tubes Very Important Paper

Angewandte

A Molecular Nanotube with Three-Dimensional
Chemie p-Conjugation**
Patrik Neuhaus, Arjen Cnossen, Juliane Q. Gong, Laura M. Herz, and Harry L. Anderson*

Dakin, L. A.; Langille, N. F.; Panek, J. S., J. Org. Chem. 2002, 67, 6812-6815.

A p-conjugated twelve-porphyrin tube is synthesizedm a cr olide 2 Abstract:a n32d% yieldt h eby aC1ʹ-C11ʹ
oxa zole
ch a in 3
intemplate-directed coupling
reaction sidethatˇC
joins iva
togethersix porphyrin
dimers,newtCh(Sch em e 1). Mott ion
for pur suforming
in g twelve
a synesis of 3 a n d
Leu ca sca n dr olide A (1) is a dou bly O-br idged, 18bonds. The nanotube has two bound templates, enclosing anapproximately
UV/Vis/NIR
st r u ct u r a l a n ainternal
loguvolume
es aofr ises
fr om4.5 nm
ou. rItsint er est in leu ca sm em ber ed m a cr olide isola t ed fr om t h e ca lca r eou s spon ge
absorption and fluorescence spectra resemble those of a preca
n
dr
olide
A’s
biologicalprofile.
At
pr
esen
t by
, it is u n der viously
reported
six-porphyrin
ring,
but
are
red-shifted
L eu cascan d ra caveolata obt a in ed fr om t h e n or t h ea st er napproximately
300
cmis, reflecting
increasedconjugation.
st
ood
t
h
a
t
m
a
cr
olide
2
r
espon
sible
for
cyt ot oxicit y,1
coa st of New Ca ledon ia in t h e Cor a l Sea . Th e r ela t ive
Ultrafast fluorescence spectroscopy demonstrates extensive
excited-stateelectronicfor
excitation
wh er ea s t h e sidech adelocalization.
in 3 is r Transfer
esponof sible
it s a n t ifu n ga l
st er eoch em ist r y of 1 wa s det er m in ed by ext en sive t wofrom an initially formed state polarized in the direction of thepr oper t ies. nanotube axis (z axis) to an excited state polarized in the xy
dim en sion a l 1 H NMR exper im en t s. Th e a bsolu t e st er eooccurs within 200 fs, resulting in a negative fluorescence
In a r ecen planet pa
per , we h a ve docu m en t ed a P d(0)ch em ist r y wa s a ssign ed t h r ou gh cor r ela t ion of t h e C5
anisotropy on excitation at 742 nm.
m
edia
t
ed
cr
oss-couplin
g of t r ifloyloxa zoles wit h vin ylst er eocen t er by em ployin g Mosh er ’s m et h od a t t h e C5
The synthesisof p-conjugated belts, barrels, and tubes has
st a n n a n es, whbecome
ich ashows
t h ainterest.
t 3 cou
ld bethe fu
r t h er divided
focus
of intense
Increasing
dimenh ydr oxyl. Leu ca sca n dr olide A exh ibit s h igh in vit r osionality of a p-system is expected to enhance the electronic
in t o t h e a ppr opr
ia t e cou
plin
g pa
r t n ers, t r ifloyloxa
zole 4delocalization,
perhapsleading
to exotic
cooperative
eleccyt ot oxicit y a ga in st h u m a n KB a n d p388 t u m or cell lin es
6 To a llevia
such as 5.
Aharonov–Bohm
oscillations,a n d a lkyn ylmtronic
et aphenomena,l speciest e difficu
lt ies
シリルアセチレンを園頭反応で導入
displa yin g low IC 50’s of 0.05 a n d 0.26 µg/m L, r espect ively.
which occur in single-walled carbon nanotubes (CNTs), buthave
notyetsynbeen tdetectedin ofmolecularmaterials.
Theassocia
t
ed
wit
h
t
h
e
h
esis
a
pot
en
t
ia
lly
u
n
st
a ble
It a lso sh ows pot en t a n t ifu n ga l a ct ivit y a ga in st Can d id a
“total synthesis” of structurally defined CNTs or 脱保護でエチニル基に
a lkyn ylm et a l bottom-up
species,wecould
exa
mmany
in ed
t h e abenefits,
pplica bilit y of aanalogous
structures
bring
technological
albican s, a pa t h ogen ic yea st t h a t a t t a cks AIDS pa t ien t s
7 In a r ecen t
because
CNTsghavedesirable
properSon oga sh ir a cou
plint ohighlyt h esesuoptoelectronic
bst r a t es.
a n d ot h er im m u n ocom pr om ised in dividu a ls.2
ties. However, the current methods for preparing them yield Pdを使った酸化的二量化でジインに
mixturesofspecieswith ndifferentchiralities,
diameters,
and is a via ble
com
m
u
n
ica
t
ion
,
it
wa
s
fou
d
t
h
a
t
t
h
is
in
deed
Recen t r epor t s in dica t e t h a t leu ca sca n dr olide A is n olengths, resulting in broad distributionsof properties.
2
bon
st
s.8
mQ.;
et h odfor t hL.
eseM.;
tefforts
ypes
of sp-sp
A.;ItGong,
Herz,
Anderson,
H.
Int. Ed. 2015, 54, 7344-7348.
Recenttowards
the rational chemical
synthesisof r u ct ionChem.
Scheme 1. Synthesis of porphyrin=
NBSdL.,=conAngew.
lon ger ananotube
va ila ble t-P12·(T6)frNeuhaus,om it s or
iginP.;
a ldibenzylideneacetone,
nCnossen,a t u r a l sou r ce.
h DDQ
a s =J.2,3-dichloro-5,6-dicyanobenzoquinone,
2. dba
3

ˇ1

[1–4]

[5]

[6, 7][8]溝呂木・Heck反応
最初の報告
HgCl
+

Li2PdCl4 2 mol%
CuCl2, NaCl
O2, HClO
OMeO
OMe 最初は有機水銀を

MeOH
RT, 24 h試薬として使用
銅共触媒を添加して触媒化

60%

Heck, R. F., J. Am. Chem. Soc. 1968, 90, 5518-5526.
Heck, R. F., J. Am. Chem. Soc. 1968, 90, 5538-5542.
PdCl2 1 mol%I
CH3COOK 1.2 equiv.
+
CH3OH
120 °C, 2 h90%Tsutomu, M.; Kunio, M.; Atsumu, O., Bull. Chem. Soc. Jpn. 1971, 44, 581-581.

Richard F. Heck
Nobel Prize 2010

Pd(OAc)2 1 mol%nBu N 1 equiv.
3

I
+

neat

ハロゲン化アリールを使うと75%
Heck, R. F.; Nolley, J. P., J. Org. Chem. 1972, 37, 2320-2322. Hgを使わなくても良い

反応機構

base·H+
base

Ar X
酸化的付加
Ar
LnPd
X

LnPd(0)

H
LnPd
X

Ar

解離

R

Ar
R

R

アルカロイド合成への応用
O
I

O

O

Bn
N

Bn
N
O

I

Bn N

O

LnPd

8 steps

LnPd

Ar

X

X
R L Pd
n

X

90%
H
N

N
Me

Overman, L. E.; Paone, D. V.; Stearns, B. A.
J. Am. Chem. Soc. 1999, 121, 7702-7703.

N
O

Ar

R

O

Pd(PPh3)2Cl2

MeN

H

O

NH
(+)-calycanthineBnカルボニル化合物のα-アリール化(温和な条件の)最初の報告
Pd2(dba)3 1.5 mol%
Tol-BINAP 3.6 mol%
NaOtBu 1.3 equiv.
Br +

O
O

Ph

Br +

93%

Pd(dba)2 7.5 mol%
DPTF 9 mol%
KN(SiMe3)2 2.2 equiv.

PhFe
P(o-tol)2
DTPF

O
94%

O

P(o-tol)2P(4-tol)2P(4-tol)2

Stephen L.
Buchwald

John F.
Hartwig

Tol-BINAP

Palucki, M.; Buchwald, S. L., J. Am. Chem. Soc. 1997, 119, 11108-11109.
Hamann, B. C.; Hartwig, J. F., J. Am. Chem. Soc. 1997, 119, 12382-12383.

エナンチオ選択的な反応への展開
Br+

Pd2(dba)3 1 mol%(S)-BINAP 2.5 mol%
NaOtBu 2.0 equiv.

O

O

N Ph

PPh2
PPh2

N Ph
85%, 94% ee

配位子を不斉配位子に変更(S)-BINAP

Spielvogel, D. J.; Buchwald, S. L., J. Am. Chem. Soc. 2002, 124, 3500-3501.
Hamada, T.; Chieffi, A.; Åhman, J.; Buchwald, S. L., J. Am. Chem. Soc. 2002, 124, 1261-1268.

全合成への応用O+

N Pd(dba) 10 mol%2
Ph (R)-Difluorophos 12 mol%
NaOtBu 2 equiv.
OMe

O

N F
Ph F

O

O
MeO

toluene, 80 °C
MeO

F
F

OMe

80% yield
94% ee

OH

O
Br

O

PPh2
PPh2

O
(R)-Difluorophos

O
H

HO

HO

O
(–)-taiwaniaquinone H

OH(–)-taiwaniaquinol B

Liao, X.; Stanley, L. M.; Hartwig, J. F.
J. Am. Chem. Soc. 2011, 133, 2088-2091.

Pd(II)からPd(0)の発生
有機金属反応剤による還元反応
X

M R

X

substitution

LnPd

R

reductive
elimination

R

–R R

LnPd

LnPd(0)

例えば園頭カップリングではジインが観測される(右図)
LnPd

LnPd
X

R2N CH2R’substitution

R2
N
LnPd
X

H

R’
X

LnPd
X

PR3
substitution

β-hydrideeliminationH

reductive
elimination

LnPd

外圏機構(outer sphere mechanism)Nu
reductive
elimination

PR3

LnPd(0) + Nu PR3
X

X

LnPd
X

LnPd(0)

X

R
R’
– N
R X

ホスフィンによる還元反応

X

+R
R

アミン類による還元反応
XR
reductive
elimination LnPd(0)

Nu

PR3
LnPd

reductive
elimination

Nu X

内圏機構(inner sphere mechanism)

LnPd(0) + Nu PR3
XR