伊藤肇集中講義（名古屋大学教員+大学院生参加の講演会)

有機ホウ素化合物の合成方法とその反応

北海道大学大学院工学研究院　伊藤　肇

名古屋大学工学部応用化学科　集中講義　 2015年5月15日

伊藤研究室（2010～）の研究

Cu catalysis (2000−)

Ir catalysis (Ishiyama, 2002−)

Si-B/base Chemistry (2012−)

J. Am. Chem. Soc., 2012, 134, 19997.

新規ホウ素化反応の開発

Ishiyama, Miyaura, Hatrwig, et al, J. Am. Chem. Soc. 2002, 124, 390.

Ar H Ar BpinIr cat.

B2pin2

X pinBCu cat.

J. Am. Chem. Soc. 2008, 130, 10044.

Nature Communications 2013, 4, 2009.

Angew. Chem., Int. Ed 2013, 52, 12828, VIP.

発光性金(I)錯体の研究

本日の講演内容

３. BBSホウ素化反応：遷移金属フリーでかつ官能基共存性のある芳香族ホウ素化合物の合成方法

1. 有機ホウ素化学の基礎

２. 銅触媒/ジボロンによるホウ素化反応：光学活性アルキルホウ素化合物の新合成方法

ホウ素－銅触媒反応系の発見（2000年）

Segawa, Y.; Yamashita, M.; Nozaki, K. Science 2006, 314, 113.

NNBBr

iPr

iPr iPr

iPr

NNBLi

iPr

iPr iPr

iPrLi, naphthalene

THF

■ホウ素アニオンは合成が困難であった。

CuCl/KOAc: Takahashi, K.; Ishiyama, T.; Miyaura, N. Chem. Lett. 2000, 982. CuX/PR3: Ito, H.; Yamanaka, H.; Tateiwa, J.; Hosomi, A. Tetrahedron Lett. 2000, 41, 6821.

+

cat. CuX PR3

DMI, rt

H3O+

OO

BB B

O

OO

O

OO

87%

■エノンへのホウ素基の形式的求核付加

CuX

BB

Cu BL

L

ホウ素-銅触媒活性種•求核的な反応特性•選択性のコントロールが可能

銅触媒/ジボロンを用いた有機ホウ素化合物の合成法を詳しく検討

過去に合成できなかった有機ホウ素化合物の新合成方法

early study:Tetrahedron Lett. 2000

BOO

J. Am. Chem. Soc. 2005J. Am. Chem. Soc. 2007

B

OR

OO

Angew. Chem., Int. Ed. 2010

BR OO

J. Am. Chem. Soc. 2010

(rac)-

R

BO

O

Angew. Chem., Int. Ed. 2008J. Am. Chem. Soc. 2010

C C CB

BuMe

H

OO


BO

O


BO

O

or

B

B

O

O

O

OJ. Am. Chem. Soc. 2013

BO

O

Org. Lett. 2012

RB

O

O

Nature Chem. 2010

Bu

BO

O

Angew. Chem., Int. Ed. 2011

B BO

OO

O

LCu X+ LCu B

O

OX B(pin)–

� ��

■

Latitar, D. S.; Tsui, E. Y.; Sadighi, J. P. J. Am. Chem. Soc. 2006, 128, 11036.

O

H1.0 mol % ICyCu(O-t-Bu)

(pin)B−B(pin), toluene

86%

O

B(pin)

B(pin)

Catalytic diboration

(pin)B−B(pin)MeOH, toluene

O

H

1.5 mol %ICyCu(O-t-Bu) OH

B(pin)

crude product

KHF2

MeOH/H2O

OH

BF3K

81%Molander, G. A.; Wisnieski, S. R. J. Am. Chem. Soc. 2012, 134, 16856.

■ Catalytic monoborylation

N N

ICy

カルボニル化合物のホウ素化

Molander, G. A.; Wisnieski, S. R. J. Am. Chem. Soc. 2012, 134, 16856.

For a review of Matteson homologation chemistry: Matteson, D. S. Tetrahedron 1998, 54, 10555.

Matteson homologation chemistry

■Stoichiometric amount of chiral auxiliary■

B O

OPh

Phn-BuLiCH2Cl2

ZnCl2THF

H

B Cl

BnOLi

THFDMSO

H

BnO B OO

Ph

Ph

OO

Ph

Ph

KHF2

MeCN/H2O H

BnO BF3K

>99% ee

75% (4 steps)

B(OH)2

HO OH

Ph Ph

Et2O

Multistep synthesis

不斉補助基を用いたαーアルコキシアルキルホウ素

H

BnO BF3K

H

BnO

N

N+Cl

CsOH•H2O (5.0 equiv)

CPME/H2O (0.5 M)105 °C

NH2PdP OTfBu

Pd catalyst(7.5 mol %)

86%, 99% ee (>99% es)

99% ee

(S)(R)

Molander, G. A.; Wisnieski, S. R. J. Am. Chem. Soc. 2012, 134, 16856.

High yield and excellent stereospecificity (>99% ee)■Various aryl halides can be used. ■

Cross-coupling reaction

鈴木カップリングで立体特異的な誘導が可能

R H

O

R = Alkyl, Ary

B BO

O O

O+

cat. Cu(I) / L*

R H

B(pin)HO

Can be asymmetric catalysis?

O

H

1.5 mol % ICyCuClB2pin2 (1.0 equiv)

3 mol % Na(O-t-Bu)MeOH (2.0 equiv)toluene, rt, 1 h1a

protection

H

B(pin)PO

H

B(pin)BnO

BnBr, NaH, THF

H

B(pin)PhOCO

PhCOOH, EDC, DMAP

H

B(pin)BnMe2SiO

BnMe2SiCl, imidazole

isolated yield (%)rac-3

conditions: conditions:33% 8% 72%

conditions:

K. Kubota

Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2015, 137, 1, 420.

不斉反応開発の7は単離方法の開発

Ph

O

1. CuCl / L* (5 mol %) K(O-t-Bu) (10 mol %) MeOH (2.0 equiv) THF, 30 °C, 6 h

2. BnMe2SiCl, imidazole CH2Cl2, 3 h

Ph HH

BnMe2SiO B

(S)NMR yield (%)

B BO

O O

O+

1.0 equiv

OO

O

O

O

O

PP

tBuOMe

tButBu

OMetBu

2

2

(R)-DTBM-SEGPHOS72%, 96% ee

O

O

O

O

PP

Me

MeMe

Me

2

2(R)-DM-SEGPHOS

71%, 32% ee(R)-SEGPHOS74%, 24% ee

O

O

O

O

PP

2

2

steric hinderance enantioselectivity

■ This is the first enantioselective nucleophilic borylation of a C=O double bond

配位子の探索：DTBMーSEGPHOSがベスト

R

O

1. 5 mol % CuCl/ (R)-DTBM-SEGPHOS K(O-t-Bu) (10 mol %) MeOH (2.0 equiv) THF, 30 °C, 6 h

2. R3SiCl, imidazole CH2Cl2, 3 h

HB B

O

O O

O+

1.0 equiv

R H

R3SiO B

(S)isolated yield (%)

OO

Ph

B(pin)BnMe2SiO

H

B(pin)Me3SiO

H

B(pin)Me3SiO

HB(pin)Me3SiO

H

70%, 96% ee 51%, 96% ee 61%, 95% ee 84%, 95% ee

B(pin)HO

H

61%, 96% ee

B(pin)HO

H

61%, 92% ee

B(pin)HO

H

B(pin)HO

HPh

Ph

trace trace

基質適用範囲の確認：フリーで単離できるものもあり

R

O

1. 5 mol % CuCl/ (R)-DTBM-SEGPHOS K(O-t-Bu) (10 mol %) MeOH (2.0 equiv) THF, 30 °C, 6 h

2. R3SiCl, imidazole CH2Cl2, 3 h

HB B

O

O O

O+

1.0 equiv

R H

R3SiO B

(S)isolated yield (%)

OO

B(pin)BnMe2SiO

HN

B(pin)Me3SiO

HNBoc Ts

81%, 95% ee 52%, 91% ee

B(pin)BnMe2SiO

HO

O

66%, 85% ee

B(pin)BnMe2SiO

H

69%, 90% ee

BzO

B(pin)BnMe2SiO

H

69%, 95% ee

BnO

良好な官能基許容性

H

O

H

B(pin)HOCuCl / L* (5 mol %)(pin)B−B(pin) (1.0 equiv)

K(O-t-Bu) (10 mol %)MeOH (2.0 equiv)THF (0.5 M), 30 °C, 6 h

Ph2MeSiClimidazole

CH2Cl2, 3 h

>99% conversionL* = (R)-DTBM-SEGPHOS

H

B(pin)Ph2MeSiO

22% yield99% ee

H

BF3KHOKHF2 (4.0 equiv)

MeOH/H2O, 30 min

71% yield

■ Poor stability of the product toward silica gel column

Good isolated yield (71%) by converting into trifluoroborate■

芳香族アルデヒドの生成物は不安定

CuCl / ligand (5 mol %)(pin)B−B(pin) (1.0 equiv)K(O-t-Bu) (10 mol %)MeOH (2.0 equiv)

solvent, 30 °C, 18 hthen Me3SiClimidazole, 3 h (R,S)

H

O

Me

TBSO

B(pin)

OSiMe3

Me

TBSO

(R,R)

B(pin)

OSiMe3

Me

TBSO

+

(R)

α-Stereocenter

ICy⋅HCl (2 mol %), toluene: 69%, (R,S):(R,R) = 30:70

(R)-DTBM-SEGPHOS, THF: 73%, (R,S):(R,R) = 89:11(S)-DTBM-SEGPHOS, THF: 77%, (R,S):(R,R) = 5:>95

■ Strong catalyst-controlled selectivity over substrate vias

基質の不斉点との干渉少ない：Catalyst Control

For a review of Matteson homologation chemistry: Matteson, D. S. Tetrahedron 1998, 54, 10555.

Sadhu, K. M.; Matteson, D. S. Organometallics 1985, 4, 1687.

Stereospecific Csp3-Csp3 bond formation; One-carbon homologation

Larouche-Gauthier, R.; Elfold, T. G.; Aggarval, V. K. J. Am. Chem. Soc. 2011, 133, 16794.

Ph H

B(pin)BnMe2SiO

96% ee

ClCH2Br n-BuLi

THF−78 °C→rt3 h

Ph H

BnMe2SiO B(pin)

92%, 96% ee

H2O2NaOH Ph H

HO OH

77%, 96% ee

chiral 1,2-diol

chiral 1,2-haloalcohol

Ph H

R3SiO Br

80%, 96% ee3,5-(CF3)2C6H3Lithen NBS, −78 °C

誘導１：Matteson ホモロゲーション

H

(pin)B OSiMe3

95% ee

(S)

Benzofuran (1.2 equiv)n-BuLi (1.2 equiv)

THF, −78 °C, 1 h

NBS (1.2 equiv)

−78 °C, 1 hthen TBAF, 2 hH

Li

H

52%, 95% ee

(pin)B OSiMe3

OOH

O

(R)

Bonet, A.; Odachowski, M.; Leonori, D.; Essafi, S.; Aggarwal, V. K. Nature. Chem. 2014, 6, 584.

Stereospecific Csp3-Csp2 bond formation; Cross-coupling with a heteroaromatic compound

誘導２：Aggarwal アリレーション

coordination

σ-bond metathesis

protonation

insertion

isomerization (racemization?)

Cu B(pin)P

P

CuB(pin)

PP

O CHR

O CCu

R

B(pin)

H

PP

O CH

R

B(pin)

H

Cu ORP

P

O C(pin)B Cu

PP

R = OMe or O-t-Bu

O CHR

(pin)B−B(pin)

MeOH

(pin)B−OR

A

B

C

D

E RH

P

P= (R)-DTBM-SEGPHOS

cf. Zhao, H.; Dang, L.; Marder, T. B.; Lin, Z. J. Am. Chem. Soc. 2008, 130, 5586.

推定反応機構

Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2015, 137, 1, 420.

北海道大学総合化学院

北海道大学大学院総合化学院

工学研究院応用化学部門

理学研究院化学部門

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＞１２０名

２０１４年より実践的計算化学という授業をスタート■ 受講者各自のノートPCに Gasssian 09Wをインストール

■ 教員がプロジェクトに映写しながらソフトの使い方を説明

■ 構造最適化、遷移状態の求め方励起状態計算の基礎を指導

K. KubotaM. Jing

■ 武次徹也教授、長谷川淳也教授伊藤、島田敏宏教授が担当

■ 伊藤研M２以上は Gaussian、量子計算が考察のツールとして使えるようになった。

Cu

B

P PO

HHH

Cu

B

P PO

H

HH

Ph Ph

Ph Ph

Ph

Ph Ph

Ph

Si-face (favored) Re-face (disfavored)

０ kcal/mol +1.04 kcal/mol

<

TS3 ((R)-SEGPHOS) TS4 ((R)-SEGPHOS)

Observed result 24%ee Relative G value

(kcal/mol) at 298 K 1.0 atm, gas phase.

B3PW91/cc-PVDZ

DFT計算による遷移状態の構造、比較

M. Jing

K. Kubota

Kubota, K.: Jing, M.; Ito, H. manuscript preparation

Cu

B

P PO

HHH

Cu

B

P PO

H

HH

Ar Ar

Ar Ar

Ar

Ar Ar

Ar

Si-face TS (favored) Re-face TS (disfavored)

Relative G value (kcal/mol) at 298 K, 1.0 atm, gas phase.

０ kcal/mol +1.97 kcal/mol

<observed result

96% ee

B3PW91/cc-PVDZ

DTBMーSEGPHOS: t-Buが効果的

Ph

O

Ph HH

BnMe2SiO B OO

R H

CuCl / L* (5 mol %) K(O-t-Bu) (10 mol %)(pin)B−B(pin) (1.0 equiv)

THF, 30 °CBHO O

OBnMe2SiClimidazole

CH2Cl2, 3 h

unstable

with MeOH: 72%, 96% eewithout MeOH: 34%, 22% ee

L* = (R)-DTBM-SEGPHOS

Mechanism

slow

isomerization

opposite enantiomer

fast protonation

O CCu

R

B(pin)PP

O C(pin)B

R

B(pin)

H

H

(pin)B B(pin)

LCu−B(pin)

O CRH

Cu

B

P P

O C RH(pin)B

Cu

PP

(pin)B B(pin)

O C RH(pin)B

B(pin)

(S)

(R)

MeOHCu OR

P

P+ O CH

R

B(pin)

H(S)

+(S)


プロトンソースがない場合は ee低下

0

I

IICu B(eg)

P

P

OC+

HH

P

P=

P

P

CuP

P

O C

B(eg)

HH

IIICuP

P

O CB(eg)HH

TSA

CuP

P

O CB(eg)

HH

P1+1.4

+6.7

-19.9

B(eg) = BO

O

Free

Ene

rgy

(kca

l/mol

)

B3PW91/cc-PVDZRelative G value (kcal/mol) at 298 K, 1.0 atm, gas phase.

-30.5

P2CuP

P

C OB(eg)

HH

TSB

TSCO

CH H

B(eg)CuP

P

O C

B(eg)

HH

CuP

P

-15.7

-1.4

isomerization step

addition step


プロトンソースなしでは異性化（ラセミ化）が進行する

B(eg) = BO

O P

P=

P

P

P1 major

0 (0)

-5.4 (-14.2)

CuP

P

O CB(eg)

HHH

OMe

IV

-2.9 (-15.0)

TSC

+1.76 (+2.9)

P2

CuO C

B(eg)

HHH

OMe

P P

Cu OMeP

P

O CB(eg)

HHH

+CuP

P

O CB(eg)

HH

MeOH+

MeOH

CuOMe

Free

Ene

rgy

(kca

l/mol

)

V

O

Cu

Me

P P

HO

CH

B(eg)

H

-4.1 (-14.4)

Relative G value (kcal/mol) at 298 K, 1.0 atm, gas phase. Electronic energies are shown in parentheses.

B3PW91/cc-PVDZ

プロトン化の活性化エネルギーは小さい

O

O

O

O

P

PCu

tBu tBuOMe

tBu

tBu

OMe

OMetBu tBu

tBuOMe

tBu

OB(pin)

Me

MeOH

+

O

O

O

O

P

PCu

tBu tBuOMe

tBu

tBu

OMe

OMetBu tBu

tBuOMe

tBu

OMe

HOB(pin)

+

０ kcal/mol -9.0 kcal/molRelative G value (kcal/mol) at 298 K, 1.0 atm, gas phase. B3PW91/cc-PVDZ

protonation

leading to more stable intermediate

熱力学支配によるプロトン化の促進

Kubota, K.: Jing, M.; Ito, H. manuscript preparation

Liu, D.; Zhao, G.; Xiang, L. Eur. J. Org. Chem. 2010, 3975.

chiral indolineindole

Enantioselective dearomatization strategy

chiral catalyst

Zhuo, C.-X.; Zhang, W.; You, S.-L. Angew. Chem. Int. Ed. 2012, 51, 12662.

NPG

R2

R3R1NPG

R4R2

R5R3

R1

NCO2H

O

CH3CH3

CO2Et

strychnine (+)-aspidospermidine pentopril

N O

N

O

HH N

NCH3

H3C

HCH3

O

(−)-physostigmine

NH

N H

H

H

ONCH3

H3C

光学活性インドリン誘導体

Hydrogenation

Electrophilic allylic substitution

Kuwano, R.; Sato, K.; Kurokawa, T.; Karube, D.; Ito, Y. J. Am. Chem. Soc. 2000, 122, 7614.

Trost, B. M.; Quancard, J. J. Am. Chem. Soc. 2006, 128, 6314.

Trost ligand

(S,S)-(R,R)-PhTRAP

FeFe

PPh2PPh2

O NH

HN O

Ph2PPPh2

2.5 mol % Pd2(dba)3CHCl37.5 mol % chiral ligand

9-BBN-C6H13 (1.05 equiv)CH2Cl2, 4 °C

NH

N+

HO

MeO

MeO

3 equiv92%, 85% ee

1.0 mol % [Rh(nbd)2]SbF61.05 mol % PhTRAP10 mol % Cs2CO3

i-PrOH, H2 (5.0 MPa)60 °C, 2 h

NAc

NAc

91%, 91% ee

芳香族のインドールから合成するのは有力な方法

N OR

O

PG R OH

Nucleophilic borylative dearomatization

Electron deficient indole

Consecutive stereogenic centers

*LCu B

N OR

O

PG

B

**

H

K. Kubota K. Hayama Kubota, K.; Hayama, K. Ito, H. Angew. Chem., Int. Ed. 2015, accepted.

世界初の方法：インドールの不斉ホウ素化

N OR

O

PG R OH

*LCu B

N OR

O

PG

B

**

H

N OR

O

PG

OH

**

H

N OR

O

PG

NH2

**

H

Nucleophilic borylative dearomatization

Stereospecific functionalizations

N OR

O

PG

C

**

H

Kubota, K.; Hayama, K. Ito, H. Angew. Chem., Int. Ed. 2015, accepted.K. Kubota K. Hayama

世界初の方法：光学活性インドリン誘導体

10 mol % Cu(O-t-Bu) 10 mol % chiral ligand10 mol % Na(O-t-Bu)

N

O

OMeCbz

N

O

OMeCbz

B(pin)

0.5 mmol

+OB

OB

O

O

2.0 equiv

t-BuOH (2.0 equiv) THF, 30 °C, 18−48 h

NMR yield (%)

PP

Me

Me

Me

Me

Me

Me

Me

Me PP

P

P

MeMe

Me

Me

(R,R)-BenzP*77%, d.r. 91:9

61% ee

(R,R)-Me-Duphos71%, d.r. 97:3

37% ee

P

P

Me

tBu

tBu

MeN

N P

P

Me

tBu

tBu

Me

(R,R)-3,5-xyl-BDPP98%, d.r. 97:3

93% ee

(R,R)-BDPP98%, d.r. 89:11

74% ee

(R,R)-QuinoxP*93%, d.r. 90:10

27% ee

Kubota, K.; Hayama, K. Ito, H. Angew. Chem., Int. Ed. 2015, accepted.

反応条件、不斉配位子の検討

N

O

OR3Cbz

N

O

OR3Cbz

B(pin)

+OB

OB

O

O

2.0 equiv

10 mol % Cu(O-t-Bu) 10 mol % (R,R)-3,5-xyl-BDPP10 mol % Na(O-t-Bu)

t-BuOH (2.0 equiv) THF, 30 °C, 4−18 h

0.5 mmol

R1

R2

R1

R2

isolated yield (NMR yield)

74% (93%)d.r. 97:3, 95% ee

64% (93%)d.r. 97:3, 95% ee

74% (96%)d.r. 93:7, 92% ee

74% (99%)d.r. 97:3, 97% ee

N

O

OMeCbz

B(pin)

N

O

OMeCbz

B(pin)

N

O

OMeCbz

B(pin)

N

O

OMeCbz

B(pin)F Cl Br MeO

76% (88%)d.r. 94:6, 93% ee

N

O

OMeCbz

B(pin)

62% (99%)d.r. 93:7, 86% ee

N

O

OMeCbz

B(pin)

Br MeO

52% (55%)d.r. 86:14, 95% ee

N

O

OEtCbz

B(pin)

71% (82%)d.r. 83:17, 89% ee

N

O

OMeCbz

B(pin)

Ph

基質の適用範囲

10 mol % Cu(O-t-Bu) 10 mol % (R,R)-3,5-xyl-BDPP10 mol % Na(O-t-Bu)

NMe

CbzN

Me

Cbz

B(pin)

0.5 mmol

+OB

OB

O

O

2.0 equiv

t-BuOH (2.0 equiv) THF, 30 °C, 24 h

not detected

LUMO -1.51 eV

LUMO+1 -0.68 eV

NO

O

Ph

O

O Me

NMe

OO

Ph

DFT analysis (B3PW91/ccpVDZ)

電子吸引基が必要：LUMOの比較

Optically active alcohol was obtained with high stereospecificity.✓

N

O

OMeCbz

B

TBSCl (2.0 equiv)imidazole (3.0 equiv)

N

O

OMeCbz

OHNaBO3•4H2O (4.0 equiv)

d.r. 97:3, 95% ee

N

O

OMeCbz

OTBS

THF/H2O, rt, air, 2 h

CH2Cl2, rt, 4 h

OO

64% yieldd.r. >99:1, 94% ee

F F

F

誘導反応：酸化

Cu BP

P

P

P= (R,R)-3,5-xyl-BDPP

(pin)B−(O-t-Bu)

σ-bondmethathesis

addition

NCbz

OOMe

Cu BPP

NCbz

O

OMeBPP

NCbz

O

OMeB

HO

HO

coordination

Cu(O-t-Bu)P

P

diastereoselectiveprotonation

HO

disfavored

favored

N

BOMe

OCbz

H

Cu

CuPP

(pin)B−B(pin)

N OMe

O

Cbz


反応機構：t-BuOHが鍵

10 mol %Cu(O-t-Bu) / L*(pin)B−B(pin)

Na(O-t-Bu)t-BuOH, THF

N

O

OR3

CbzN

O

OR3

Cbz

B OO

R1

R2

R1

R2

up to 97:3 d.r.up to 99%up to 97% ee

N

O

OMeBoc

N

O

OMeBoc

B(pin)

0.5 mmol 45%, d.r. 54:46

10 mol % Cu(O-t-Bu)10 mol % Xantphos(pin)B−B(pin) (2.0 equiv)

20 mol % K(O-t-Bu)t-BuOH (2.0 equiv) THF, 30 °C, 11 h

N

O

OMeBoc

54%, d.r. 57:432 stereoisomers

OH

Ph

toluene60 °C, 16 h

Ph

O

H(3.0 equiv)

The first enantioselective borylative dearomatization of heteroaromatic compounds has been achieved.

L* = (R,R)-xyl-BDPP

PP

MeMe

MeMe

Me

Me

Me

Me

Current study

インドールの脱芳香族ホウ素化


■ シリルボラン／塩基法　遷移金属フリーのホウ素化

92% yield

(1.5 equiv)KOMe (1.2 equiv)

DME, 30 °C, 1 h

Si BO

O

Br BO

O

Ph

Yamamoto, E.; Izumi, K.; Horita, Y.; Ito, H. J. Am. Chem. Soc. 2012, 134, 19997.

Dr. E. Yamamoto

Y. Horita K. Izumi

■ 有機リチウムやGrignard試薬利用

B

X LiBuLi

BX

官能基許容性に問題あり

■ 宮浦パラジウム触媒法

XPd cat.

B B

B

パラジウム触媒の残存立体障害に弱い、反応が遅い

C(sp２)ーX へのホウ素置換反応

シリルボランの性質シリルボランは塩基による活性化でケイ素求核剤となる

OB

OSiMes

MesOMe Si

Mes

MesOMeLi

BuLi (2 equiv)toluene–78 °C, 1 h

Me3SiCl (2.45 equiv)

SiMes

MesOMeMe3Si

88% yield

Kawachi, A.; Minamimoto, T.; Tamao, K. Chem. Lett. 2001, 1216.

Chiral NHC (10 mol%)

OB

OSi Ph R1

O

R2

1

R1

O

R2

Si

up to 98% yieldup to 98:2 er

R1 = alkyl, aryl, OMe, H

DBU (15 mol%)

Ph

N N

Ph Ph

Ph Ph

Me Me

Chiral NHC

O'Brien, J. M.; Hoveyda, A. H. J. Am. Chem. Soc. 2011, 133, 7712.

Si BO

OPh + RO–M+

Si BO

OPhOR

Si BO

OPhOR

Brbase (1.2 equiv)

solvent, 30 oC , 1 h

B(pin)

MeO MeO

SiMe2Ph1

MeO

OB

OSi Ph

(1.5 equiv)

なぜか芳香族ハロゲン化物のホウ素化が進行！

Yamamoto, E.; Izumi, K.; Horita, Y.; Ito, H. J. Am. Chem. Soc. 2012, 134, 19997.

baseLiOMeNaOMeKOMeKOtBuK2CO3

KFDBU

B/Si

80:2095:573:27

total yield (%)0819266000

bSolvent: DME

“tBuO”では選択性・収率低下

ナトリウムでは選択性低下

アルコキシド塩基：カリウムメトキシドがベスト

BBS法と名付けた base promoted borylation with silylborane

山本英治博士

良好な収率で反応が進行する。早い（一時間以内完結)

Yamamoto, E.; Izumi, K.; Horita, Y.; Ito, H. J. Am. Chem. Soc. 2012, 134, 19997–20000.

官能基や立体障害があってもスムーズに反応が進行する

B(pin)

R' = H, 64(85)%

B(pin)

50(84)%OS

B(pin)

63(78)%R'

R' = Ph, 62(87)%

Yamamoto, E., Ukigai, S., Ito, H. Chem. Sci. 2015, 6, 2943 - 2951.

官能基や立体障害があってもスムーズに反応が進行する

B(pin) B(pin)Me Me

72% (isolated) 85% (isolated)

Murata, M.; Smbommatsu, T.; Watanabe, S.; Masuda, Y. Synlett. 2006, 1867.

Br B(pin)H-B(pin) (2.0 equiv)Pd(dba)2, t-Bu-DPEphos (5 mol%)

1,4-dioxane, Et3N (3.0 equiv)100 ºC, 6 h

72% (isolated)

O(t-Bu)2P P(t-Bu)2

t-Bu-DPEphos:

Br B(pin)PMe2Si B(pin) (1.5 equiv)KOMe (1.2 equiv)

DME, 30 ºC, 1 h

92% (NMR)82% (isolated)

BBS法はヘテロ環化合物についても適用可能


(87)% 58(63)%

NNBn

B(pin)

ON

B(pin)

S B(pin) NN

B(pin)N

O

B(pin)

Ph Ph59(68)% 67%c 51d(74)%

52%

B(pin)

S

(77)%74(85)%

OB(pin)N

Et

B(pin)

61(75)%S

B(pin)

N

SEt B(pin) N

N

B(pin)N

N

B(pin) N

N

B(pin)

MeO N46(68)%

not detected(38)% 73%

S. Ukigai

BBS法はヘテロ環化合物についても適用可能


(66)%

N

B(pin)

58%

N

B(pin)

N(1.0 equiv) 3w 20% isolated yield

KOMe (1.2 equiv)

DME, 30 oC, 1 h

PhMe2Si–B(pin) (1.5 equiv)

N SiMe2Ph

N SiMe2PhR

work-upborylationconditions

■ シリル付加が収率を下げるケースもある。

アルケニルハライドは立体特異的に変換される


Si-B equiv base solvent yield of B (%) Z/E B/Si

1.5 KOMe DME 53 92:8 95:5

1.5 NaOMe DME 72 96:4 96:4

1.5 NaOEt DME 79 97:3 96:4

2.0 NaOEt DME 89 97:3 96:4

2.0 NaOEt 1,4-dioxane 81 98:2 99:1

2.0 NaOEt CH2Cl2 2

2.0 NaOEt toluene 0

PhMe2Si–B(pin)Base (1.2 equiv)

solvent, 30 ˚C, 1 h

CyI

CyB(pin)

CySiMe2Ph

Z/E = 98:2



DME, 30 ˚C, 1 hAlkenyl X

NaOEt (1.2 equiv)Alkenyl B(pin)

X = Br, I

PhMe2Si–B(pin) (2 equiv)

B(pin)Cy

B(pin)

B(pin)Ph

B(pin)

OMOM

B(pin)

B(pin)B(pin)

B(pin)O 5

B(pin)O

B(pin)

Ph

Ph

O

OBuO

B(pin)

Cy

(E)-6a, X = I, 68% (Z)-6b, X = I, 72% (Z)-6c, X = I, 64%

(Z)-6g, X = I, 51(70)% (Z)-6h, X = I, 74%

6d, X = Br, 43%

(E)-6e, X = I, 64% 6f, X = Br, (60)%

6j, X = Br, 68%6i, X = B, 58%r 6k, X = Br, 53%

OPh

O

5

アルケニルハライドは立体特異的に変換されるi) 1 (1.5 equiv)

KOMe (1.2 equiv)DME, 30 ˚C, 1 h

2 4Ar–B(pin)Ar–Br

3

Pd(PPh3)4 (5 mol %)

K2CO3 (2 equiv)solvent, temp.

Ar'–I (2 equiv)Ar–Ar'

ii) TBAF treatment

NO2NC

4x, 36%b

4l, 74%c

N

NN

4t, 78%d

O

NO2

4h, 84%b

NO2S

N4u, 64%d

N4v, 58%d


1 (1.5 equiv)KOMe (1.2 equiv)

DME, 30 ˚C, 1 h

3y, 61(51)%a

NN

Br

NBoc

NN

B(pin)

NBoc

2yN

NHN

NNH2

OCl

Cl F

Crizotinib(anti-cancer drug)

N

NNBocN Br

1 (1.5 equiv)KOMe (1.2 equiv)DME, 30 ˚C, 1 h

N

NNBocN OH

2z

ii) oxidation

3z, 71%a

N

NNBocN B(pin)

N

NNBocN O

SO

O

GPR119 agonist

■ Key Features of Boron Element

NN

PtOO

B

Wang, Suning et al. Chem. Commun. 2011.

■ Triarylboron-‐‑‒Containing Materials

N B N BB

BS

SB

n

Shirota, Y et al. J. Am. Chem. Soc. 1998.

Doty, J. C.; Babb, B.; Grisdale, P. J.; Glogowski, M.; Williams, J. L. R. J. Organomet. Chem. 1972, 38, 229.

含ホウ素有機電子材料：トリアリールボラン

K. IzumiDr. E. Yamamoto

BBS法をトリアリールボランに適用

base solvent temp. (℃) yield (%) B/Si

KOMe DME 30 28 39:61

NaOMe 1,4-dioxane 50 76 77:23

Na(O-t-Bu) 1,4-dioxane 50 78 87:13

Na(O-t-Bu) 1,4-dioxane/hexane (1:1) 50 80 90:10

Si B

Et Brbase (1.2 equiv), 24 h

BEt SiEt+

含ホウ素有機電子材料：トリアリールボラン

manuscript under preparation

MeO BMes

Mes

94% yield (90% purity)B:Si=88:12 (NMR)61% isolated yield

B

Me

Mes

Mes

90% yield (NMR)B:Si=92:8 (NMR)66% isolated yield

F3C BMes

Mes


B

Me

Mes

Mes

46% yieldB:Si=67:33 (NMR)20% isolated yield

N BMes

Mes


NMe B

Mes

Mes89% yield (NMR)B:Si=93:7 (NMR)62% isolated yield

Cl BMes

Mes


BMes

Mes


BSS Mes

Mes


Me

Br BMes

Mes


Me

Br

BMes

Mes


安定なシリルボラン：スーパーシリルボラン

manuscript under preparation

■ 最大の欠点：空気に不安定

PMe2Si B(pin) PMe2Si OB(pin)Air

R. Shishido


R1: 0.096�GOF: 1.06 �

Space Group P21/c (#14)�

ホウ素化で同等以上の性能

BBS法の反応機構は？

■ なぜ (形式的)求核的芳香族置換反応が進行するのか？

■ なぜケイ素でなくホウ素へ置換されるのか？

■ 官能基許容性はなぜ生じるのか？

■ なぜ立体障害に強いのか？

反応機構、四つの可能性

1. 遷移金属のコンタミネーション

Ph Br

Si–B

base

２. アニオンラジカル経由

３. 中性ラジカル経由

４. アニオン経由

Ph B(pin)

Br

遷移金属の触媒作用ではないPd, Cu, Fe, Ni, Rh, Ag, Co, Pt, Ru, Ir　の添加による加速効果は見られず

KOMe 試薬のICP発光分析遷移金属は検出限界以下

Yamamoto, E.; Izumi, K.; Horita, Y.; Ito, H. J. Am. Chem. Soc. 2012, 134, 19997–20000.

反応機構に関する実験：遷移金属コンタミネーション？

このような反応は、どのような遷移金属の触媒反応においても、知られていない

一電子移動＆アニオンラジカル経由の機構

I+

K(O-t-Bu) (3 equiv)EtOH (cat)

DMF, 80 °C, 2 h73%

Shirakawa, E.; Zhang, X.; Hayashi, T. Angew. Chem., Int., Ed. 2011, 50, 4671.

X+

IO-t-Bu

I

Php-Tol Ph

RO– M+

Si BO

OPh

OBO

OR

SiPh

M X X

Si BO

OPh OR Si B

O

OPh RO

? ?

反応速度の比較で電子移動を考察：関与ない？

Br

KOMe (1.2 equiv)

DME, 30 ˚C, 15 min

F3C

PhMe2Si–B(pin)(1.5 equiv)

Br

Ph

B(pin)

F3C

B(pin)

Ph3d, 7% yield

3a', 52% yield

reduction potential: lower

reduction potential: higher

electrophilicity of C1: lower

electrophilicity of C1: higher

1

1

2d (1.0 equiv)

2a' (1.0 equiv)

3d:3a' = 15:85


別のラジカル経由のパスがあるかもしれない。

ラジカル反応の可能性は？：関与の可能性は低い

ラジカル反応の可能性は？：関与の可能性は低い

CyI

CyB(pin)

Cy

(Z)-6a (E)-6a

Cy H CyH

fast

B(pin)

(Z)-5a

silylborane/alkoxy baseborylation with

反応機構、四つの可能性

1. 遷移金属のコンタミネーション

Ph Br

Si–B

base

２. アニオンラジカル経由

３. 中性ラジカル経由

４. アニオン経由

Ph B(pin)

Br

AFIR自動反応経路探索: 北海道大学前田・武次先生

Ref: 前田理、畑中美穂、植松遼平、武次徹也、諸熊奎治人工力誘起反応法による化学反応経路の自動探索: 有機合成化学への応用と展望有機合成化学協会誌, 2014, 5, 567.

Dr. S. Maeda Pro. T. Taketsugu

RO– M+

Si BO

OPh X

R. Uematsu（天然物合成経験あり）

M06-L/6-311+G(2d,p), 303.15K, 1.0 atm

Uematsu, R., Yamamoto, E., Maeda, S., Ito, H., Taketsugu, T. J. Am. Chem. Soc. 2015, 137, 4090.

ハロゲンへのアタックとアリールアニオン生成が鍵

なぜケイ素でなくホウ素へ置換されるのか？官能基許容性はなぜ生じるのか？なぜ立体障害に強いのか？


RO– M+

Si BO

OPh

OBO

OR

SiPh

M

BrAr

Si BrPh

OBO

OR

Ar

MB

O

OAr

– MBr

B OO

O

R

M

Ar

BrSi

MeMePh

– ROSiMe2Ph

R = Me, EtM = K, Na

ArBr

OBO

RO

SiPh

M

M06-L/6-311+G(2d,p), 303.15K, 1.0 atm

なぜケイ素でなくホウ素に置換されるのか？

ArBr

OBO

RO

SiPh

M B OO

O

R

M

Ar

BrSi

MeMePh

Ar

HBr

OBO

RO

SiPh

M

ΔG‡: 18.4 kcal/mol0 kcal/molΔG: -11.7 kcal/mol

B OO

O

R

M

Ar

BrSi

MeMePh

BO

OAr

ΔG‡: 1.0 kcal/mol

B OO

O

R

M Ar

Br Si MeMe

Ph

Ar SiMe2Ph


■ この活性化エネルギーが非常に小さい ”アリルカリウム”が迅速に消費される。＝官能基許容性が高い

M06-L/6-311+G(2d,p), 303.15K, 1.0 atm


なぜ立体障害に強いのか？

ArBr

OBO

RO

SiPh

M B OO

O

R

M

Ar

BrSi

MeMePh

Ar

HBr

OBO

RO

SiPh

M

ΔG‡: 18.4 kcal/mol0 kcal/molΔG: -11.7 kcal/mol

B OO

O

R

M

Ar

BrSi

MeMePh

BO

OAr


B OO

O

R

M Ar

Br Si MeMe

Ph

Ar SiMe2Ph


■ ハロゲンアタックが律速段階

profiles provided several points that can be beneficial for furtheroptimization of the BBS method.At first, the activation energy in the halogenophilic attack on

sterically hindered 2,4,6-triisopropylbromobenzene (3e) was inves-tigated and found to be reasonably low (ΔΔG⧧ = 1.9 kcal/mol,Figure 4). TS(B2′/B3) was slightly lower than TS(B3/B4) for 3e

as shown in Figure S5-1, and the reaction thus is expected toproceed smoothly with 3e. This is consistent with the highreactivity of the BBS method toward sterically hinderedsubstrates.2

Second, the halide effect [PhBr (3b) vs PhCl (3f) vs PhI(3g)] and substitution effect of para position [PhBr (3b) vsp-MeO−C6H4Br (3h) vs p-F−C6H4Br (3i)] were investi-gated experimentally and theoretically (see the SupportingInformation: S11 for experimental data and Figures S5-2, S5-4,S6-2, and S6-3 for theoretical energy profiles.) Experimentally,it was shown that the reactivity increases as 3g > 3b > 3f and3i > 3b > 3h.26 These experiments also showed that reactionsof different substrates are in competition when two substratesare combined together. Consistently, ΔG⧧ values at the rate-determining TS(B2′/B3) are very close to each other for thesesubstrates; ΔG⧧ values at TS(B2′/B3) are 7.5, 8.7, 7.3, 6.9, and7.2 kcal/mol for 3b, 3f, 3g, 3h, and 3i, respectively, in our bestestimate with inclusion of the solvent effect by C-PCM. Thesevalues reproduce the experimental reactivity trends qualita-tively; only the ΔG⧧ for 3h showed deviation from theexperimental trend. Nevertheless, these <1 kcal/mol energydifferences are too small to be discussed with the presentcomputational level. Moreover, the computational trendchanged by inclusion of the solvent effect with C-PCM (seeSupporting Information). Treatment with more accurate abinitio theory and explicit consideration of movements ofsurrounding solvent molecules are required for furtherquantitative predictions.Third, the impact of the base is investigated. We reported

that KOMe (2a) gave the borylation and minor silylationproducts of p-MeO−C6H4Br (3h) in 92% yield with high B/Siratio (95:5). The reaction with NaOMe (2c) resulted in 81%yield (5b + 6b) with a B/Si ratio of 80:20. We also foundthat the borylation of PhBr (3b) with K(O-t-Bu) (2d) andLi(O-t-Bu) (2e) as the base gave moderate to high yield andB/Si selectivity [66% yield (5b + 6b), B/Si = 73:27; 94% yield(5b + 6b), B/Si = 85:15, respectively] under previouslyreported reaction conditions.2 Theoretical results showed thatall of the bases shown in Scheme 4 provide ΔΔG⧧ values thatare low enough to promote the borylation reaction. However, itis difficult to fully elucidate the reactivity and selectivity trends

of the experimental results. This is probably because of thesolubility difference of the bases (for details, see Figure S10 inthe Supporting Information). KOMe (2a), LiOMe (2b), andNaOMe (2c) are only partially soluble in dimethoxyethane,whereas K(O-t-Bu) (2d) and Li(O-t-Bu) (2e) are fairly solublein the solvent. It is noteworthy that the reaction of LiOMe (2b)afforded no borylation/silylation products in the experiment,although the theoretical results for LiOMe indicate its moderatereactivity. This inconsistency is attributable to the very slowSi−B bond cleavage in the real LiOMe reaction system becauseof the extremely low solubility of LiOMe in the reactionmedium and relatively higher ΔΔG⧧ value at the Si−B bondcleavage step (B2′ → B3) (for details, see the SupportingInformation). Furthermore, in this study, we optimized TSsobtained for the reaction with 2a after substituting thecorresponding metal atom without further conformationalanalysis. The B/Si selectivity would be determined by a subtleenergy gap between the silylation TS and the borylation TS,and its quantitative prediction further requires an extensiveconformational sampling. Such an analysis for quantitativediscussions of the B/Si selectivity will be a future subject.

■ DISCUSSIONThe pathways computed in the current study for the case-A andcase-B reactions provide adequate explanations of many of thecharacteristic features of the BBS method. The BBS methodwas initially highlighted for its good functional groupcompatibility and high reactivity toward sterically hinderedsubstrates.2 In the reaction profiles shown in Figures 1 and 3,the step involving the cleavage of the Si−B bond throughTS(AorB2′/AorB3) was identified as the rate-determining step.The reaction proceeded rapidly beyond this point, withunstable intermediates such as the silyl anion and carbanionspecies being immediately consumed with very low energybarriers (see the steps from AorB3 to AorB5 in Figures 1 and 3).This result indicated that all of these intermediates almostexclusively underwent the borylation reaction, even when theycontained other reactive functional groups. Furthermore, thestructures of the TSs involved in these steps provide somerationale for the high borylation reactivity observed in theBBS method toward sterically hindered aryl bromides. TheTS(B3/B4) structure shows that the steric hindrance providedby the substrate would be too far removed from the reactiveσ*(C−Br) orbital to have a noticeable impact on the reactivity,whereas catalysts usually interact with the carbon and bromoatoms in the C−Br bond directly in the transition metal-catalyzed boryl substitution of aryl bromides. Actually, a bulkysubstrate 3e showed a reasonable potential profile with lowbarriers.The BBS method proceeded to give a product with a

counterintuitive borylation reaction as well as a small amount ofthe silylation product (5−10%).2 This distribution of productssuggests that these two channels are competing with each otherand that the energy barrier for the borylation reaction must beslightly lower than that of the silylation reaction by a fewkcal/mol. This feature of the BBS method was effectivelyreproduced in the current reaction profiles. Furthermore, theresults of simple thermodynamic analyses on the basis of theirfree energy barriers and Boltzmann distributions predictedborylation/silylation ratios of the case-A and case-B reactions tobe 97:3 and 92:8, respectively. These ratios were qualitativelyconsistent with the experimental ratios of 91:9 and 94:6. Theenergy profiles for these reactions showed that all of the

Figure 4. TS structures, free energies (ΔG⧧) relative to the reactants(1, 2a, and 3b/3e), and activation free energies (ΔΔG⧧) for the halo-genophilic attack reaction steps. Free energy values (303.15 K, 1.0 atm)based on M06-L/6-311+G(2d,p) calculations are given in kcal/mol.

Journal of the American Chemical Society Article

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改めてアリールアニオン種発生の確認

the detachment/attachment coordinate of 3b at B2′ was−20.9 kcal/mol. This is much lower than TS(B2′/B3). Theprofile shown in Figure 2 thus is the best path concerning exis-tence or nonexistence of 3b. Details of this analysis are de-scribed in Supporting Information Figures S4, S6-1, and S6-2.Decomposition of reaction complexes with dissociation of

species that do not directly participate in the reaction can be afavored process. However, this is not the case in the reactionsteps from B3 to B5 and B7 of the present reaction. This isbecause activation free energies required in these steps are allvery low. In other words, these steps proceed rapidly beforedissociation of such species. In order to confirm this, we calcu-lated free energy values along dissociation coordinates of thesespecies. For example, for reaction complex B4, the distanceRK−B between the K atom and the B atom in (pin)B−OMe waschosen as the dissociation coordinate of (pin)B−OMe. Then,we performed a constrained optimization, fixing the distanceat RK−B = 8 Å and the normal-mode analysis for the pro-jected Hessian. This gave an estimate of the free energy of−27.0 kcal/mol at RK−B = 8 Å. This is much higher than theTSs for the forward reactions: −35.3 kcal/mol for borylationand −33.9 kcal/mol for silylation. Thus, the reaction proceedsbefore dissociation of (pin)B−OMe. In this way, we confirmedthat the reaction proceeds with the path from B3 to B5 and B7shown in Figure 3 without dissociation of any species. Details ofthis analysis are described in Supporting Information Figure S6-1.The possibility of radical reaction pathways was checked

using several calculations. Strohmann et al.14a suggested theexistence of a radical-mediated pathway in the reaction of silylanions with organic halides, which is mechanistically relatedto the BBS method,14a and TS(B3/B4), which involves thehalogenophilic attack step, that could possess some radicalcharacter. The results of a CIS-based MO stability check22 atthe UM06-L/6-311+G(2d,p) level, however, indicated thatTS(B3/B4) was closed-shell at the electronic ground state.Furthermore, TDDFT-based electronic excitation energycalculations for the complex composed of B2 and PhBrrevealed that the closed-shell electronic ground state was wellseparated from the first electronic excited state by 103.6 and122.2 kcal/mol at the CAM-B3LYP23/6-311+G(2d,p) andLC-BLYP24/6-311+G(2d,p) levels, respectively. These resultstherefore excluded the possibility of an open-shell radicalspecies being involved in this reaction.A significant difference was found between the case-A and

case-B pathways in terms of the complexes containing theanionic intermediates PhCH2CH2

− and Ph− (A4′ and B4). Inthe case-B reaction, cleavage of the C−Br bond resulted inthe formation of the stable intermediate B4 bearing a K−Cbond. The interaction between the terminal C atom of thePhCH2CH2

− anion and the potassium cation in A4′ wasweakened, however, by the strong interaction between thepotassium cation and the Ph group, which separated thepotassium cation from the terminal C atom. The relativelystrong interaction between the potassium cation and the Phgroup of the PhCH2CH2

− anion could explain why themetastable intermediate A4′ was identified as a local potentialenergy minimum in the case-A reaction.In a similar manner to the case-A reaction, the case-B

reaction also involved two reaction pathways at B4 (i.e.,borylation and silylation reactions). Experimental resultsshowed that the borylation reaction occurred in preference tothe silylation reaction. This preference can be understood interms of the difference in the free energy values of TS(B4/B5)

and TS(B4/B7), with the former being 1.4 kcal/mol lower inenergy than the latter. This energy difference was very similarto the corresponding energy gap of 1.5 kcal/mol in the case-Areaction. Taken together, these results indicated that theborylation reaction was kinetically favored over the silylationreaction. On the basis of this free energy gap and theBoltzmann distribution, the B/Si branching ratio of the case-Breaction was estimated to be 92:8, and this ratio was consistentwith the experimental borylation/silylation ratio of 94:6 fromthe BBS method.

Experimental Results. The validity of the proposed arylanion-mediated mechanism was supported by the results of anexperiment involving the borylation of an aryl halide (3c) bearinga TBS ether group next to its bromine atom (Scheme 3a). The

reaction of 3c with silylborane 1 in the presence of potassiummethoxide proceeded as an intramolecular silyl substitutionreaction instead of a boryl substitution reaction to give TBS-substituted product 12c in moderate yield (53% isolated yield),without detection of borylation product 5c. This resultsuggested that the corresponding aryl anion species wasgenerated in situ and that this species subsequently attackedthe silicon atom of the proximal TBS group at a greater ratethan the boron or phenyldimethylsilyl electrophile derived fromthe silylborane. It is noteworthy that Hudrlik et al.25 recentlyreported an intramolecular retro-Brook rearrangement, whichproceeded via a similar mechanism (Scheme 3b).

Substrate and Base Dependence. We now have themajor reaction path for the BBS method. Thus, it would beinteresting to look at energy profiles of this path for differentsubstrates and bases. In practice, five aryl halides, 3e−3i, andfour bases, 2b−2e, listed in Scheme 4 were considered. In the

Supporting Information, all computed energy profiles arecompared in Figure 3. Some trends seen in these energy

Scheme 3. Intramolecular Retro-Brook Rearrangement of aSilylborane Species in the Presence of an Alkoxy Base

Scheme 4. Aryl Halides and Bases Used in Discussions onthe Reactivity of the BBS Method

Journal of the American Chemical Society Article

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MeO

SiMe2Ph8d', 51% GC yieldSi LiPh

p-MeOC6H4Br(1 equiv)

THF, 30 ˚C, 1 h

Si LiPh Br OMe Si BrPh OMeLi

AFIR/DFTによる反応機構解析

■ なぜ (形式的)求核的芳香族置換反応が進行するのか？

● アリールアニオン種の生成

■ なぜケイ素でなくホウ素へ置換されるのか？

● アリールアニオン種のホウ素中心への攻撃のほうが速い

■ 官能基許容性はなぜ生じるのか？

● アリールアニオン種の寿命が短い

■ なぜ立体障害に強いのか？

● 律速段階のハロゲンへの攻撃が立体障害から離れている

最新設備：フロンティア応用科学研究棟

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ご協力いただいた先生方への謝辞

1. ホウ素化反応（銅触媒、BBS法）

２. メカノ応答性をもつ発光性金錯体

澤村正也教授　鈴木孝紀教授武次徹也教授

前田理准教授谷野圭司教授

北海道大学

喜多村曻教授石坂昌司准教授（現広島大学）日夏幸雄教授分島亮准教授朝倉清高教授佐々木陽一名誉教授

加藤昌子教授柘植清志教授（現富山大学)　稲辺保教授小西克明教授長谷川靖哉教授　

榊茂好京都大学名誉教授中尾嘉秀准教授(京都大学）矢貝史樹准教授（千葉大学）

関修平教授（大阪大学）オラフカートハウス教授（千歳科技大）

北海道大学

細見彰筑波大学名誉教授　　　　今本恒雄千葉大学名誉教授

謝辞

￥研究資金￥科学研究費補助金　基盤研究(B) 特定領域研究(元素相乗系の化学)

挑戦的萌芽研究 JST さきがけ(物質と光作用) 最先端・次世代研究開発プログラム

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仲　崇民佐々木　悠祐大倉　拓真國井　峻堀田　優子榑沼　紗也佳宮　貴紀室本　麻衣久保田　浩司

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伊藤肇 集中講義（名古屋大学 教員+大学院生参加の講演会)

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Transcript of 伊藤肇 集中講義（名古屋大学 教員+大学院生参加の講演会)

伊藤肇集中講義（名古屋大学教員+大学院生参加の講演会)

Transcript of 伊藤肇集中講義（名古屋大学教員+大学院生参加の講演会)