S7-3 分子状水素による極性官能基還元のための触媒分子設計

東京工業大学大学院理工学研究科

伊藤 正人

2007年9月25日錯体化学討論会シンポジウム「錯体触媒化学の新展開」

HYDROGENATION OF KETONE WITH Cp*Ru COMPLEXES

Organometallics, 2001, 20, 379.

RuCl

O

2-propanol+

Cp*RuCl(cod)

30 °C, 1 h1 atm

H2 KOHH OH

Ketone : Ru : Ligand: KOH = 100 : 1 : 1 : 1

Ligand

Cp*RuCl(cod)

LigandNH2

NMe2

conv. (%)

NH2

NHMe

NH2

NH2

NH2

N

NH2

PPh2

NMe2

NMe2

>99 98 41 37 16

NHTs

NMe2

OH

NMe2

SH

NMe2

ineffective

Ru+

Me2N NH

H

(OR)–

RuMe2N

NH O

H

H

R

HRu

Me2NN

HHRu

Me2NN

H

H2 ROH

H

OR2

R1

HOR2

R1

HROH

Cp*RuCl(cod)

Me2N NH2

basicROH

ALCOHOL–ASSISTED DIHYDROGEN CLEAVAGE

Organometallics, 2001, 20, 379.Brandt and Andersson J. Am. Chem. Soc., 2005, 127, 15083.

ASYMMETRIC HYDROGENATION WITH CHIRAL Cp*Ru(NN)

Cp*RuCl(NN)

Ru

N N

Cl

Organometallics, 2001, 20, 379.

*R R'

O

R R'2-propanol+

Cp*RuCl(NN)

30 °C, 6–18 h1—20 atm

up to 1170 TOF h-1 (product mols/cat mol)

H2 KOH H OH

Ru : KOH = 1 : 1

O

79% ee

O

81% ee

O

95% ee

O

85% ee

O

79% ee

O

79% ee

M+

LN

HH

(OR)–

ML

NH O

H

H

R

HM

LN

HHM

LN

H

H2 ROH

H

B A

ROHH

ABH

Cp*M(amine) COMPLEXES FOR POLAR HYDROGENATION

aldehyde, ketone, epoxide, imide, ester, amide, carboxylic acid etcB A

FeNCMe

L

NH2

CoI

L

NH2

IrCl

L

NH2

RhCl

L

NH2

RuNCMe

L

NH2

+

+ + +

+

NH2

L

NH2

NMe2

NH2

N

NH2

PPh2

Cp*M(amine) COMPLEXES FOR POLAR HYDROGENATION

PREPARATION OF Cp*RuCl(amine) COMPLEXES

ClRu

NR2

NH2 L

NH2

RuCl

Ar2P

NH2

PAr2

NH2 Cp*RuCl(isoprene)1/4 [Cp*RuCl]4

RuCl

R2N

NH2

Rn RnRuCl

N

NH2

81–99% yield

Et2O CH2Cl2

HYDROGENATION OF EPOXIDE WITH Cp*RuCl(LN) COMPLEXES

n-C6H13 n-C6H132-propanol+

Cp*RuCl(LN)

30 °C, 4 h10 atm

H2 KOt-Bu

Epoxide : Ru : KOt-Bu = 100 : 1 : 1 Cp*RuCl(LN)

LNNH2

NMe2

conv. (%)

NH2

N

NH2

PPh2

<1 <1 >99

OOH

RuCl

L

NH2

NH2

PPh2

87

PPh2

71

NH2

Organometallics, 2003, 22, 4190.

MOLECULAR STRUCTURES OF Cp*RuCl(amine) COMPLEXES

RuCl

H2N

NEt

P212121(#19)R1(wR2)=0.034(0.034)

Ru

N1N2

Cl

Selected bond lengths [Å]

Ru—N1 Ru—N2 Ru—Cl

2.159(5)2.306(5)2.524(2)

P21(#4)R1(wR2)=0.034(0.087)

Ru—N Ru—P Ru—Cl

2.194(5)2.2816(11)2.470(2)

Selected bond lengths [Å]

Ru

N

PCl

Organometallics, 2003, 22, 4190.

RuCl

Ph2P

NH

MOLECULAR STRUCTURES OF [Cp*RhCl(amine)]+ COMPLEXES

P21/n(#14)R1(wR2)=0.036(0.122)

Rh

N1

N2 Cl

Rh

N

P Cl

Selected bond lengths [Å]

Rh—N1 Rh—N2 Rh—Cl

2.124(3)2.182(3)2.4337(8)

P21/n(#14)R1(wR2)=0.035(0.113)

Rh—N Rh—P Ru—Cl

2.124(3)2.3089(8)2.4031(6)

Selected bond lengths [Å]

RhCl

Me2N

NH2

Cl

RhCl

Ph2P

NH2

Cl

PREPARATION OF [Cp*Ru(amine)]OTf COMPLEXES

Organometallics, 2003, 22, 4190.

RuCO

Ph2P

NH2

RuCO

Me2N

NH2

IR (νC≡O) 1931 cm-1 1938 cm-1 1948 cm-1

RuCO

N

NH2

13C NMR (C5Me5) 93.0 ppm91.7 ppm 95.5 ppmelectron density on Ru center decrease

NCMeMeCN

MeCNRu

NCMeRu

L

NH2L

NH2

L2

L2Ru

L

NH2

92–99% yield86–93% yield

CH2Cl2 CH2Cl2

L2: COCNXyPPh3

+ + +

Me2N

RuCl

Ph2P

NH2

aldehydeketone

esterlactonecarboxamidecarboxylic acid

epoxideimide

Cp*Ru(NN) Cp*Ru(PN)

H2

XX

O

X

OXX

X

XX

O

X

OOO

X

PH2 = 1 –30 atm, catalyst = Ru + base (1:1)[substrate] = 0.02 –0.6 M in 2-propanol30 –80 °C

RuCl

N

NH2

RuClN

H2

REDUCING ABILITY FOR POLAR FUNCTIONAL GROUPS

Chem. Commun. (Feature Article), 2007, in press

HYDROGENATION OF IMIDE WITH Cp*Ru(PN) CATALYSTS

PPh2

NH2

PPh2

NH2

+ H2 2-propanol80 ºC, 2 h

Cp*Ru(PN)KOt-Bu

imide:Ru:KOt-Bu = 100:1:1, [imide] = 0.33 M in 2-propanol

10 atm

PPh2

NH2

67>99% conv. 64

NCH2Ph

O

O

NCH2Ph

CH2

O

OH

RuX

P

N

Cp*Ru(PN)

(X = Cl, MeCN +)

H

PPh2

NMeH

21

J. Am. Chem. Soc., 2007, 129, 290.

APPLICABLE IMIDES

+ H2 2-propanol80 ºC, 1–18 h

Cp*RuCl(PN)KOt-Bu

Ru:KOt-Bu = 1:1 (1 –5 mol%)[imide] = 0.02 –0.20 M

30 atmRu

Cl

Ph2P

NH2

Cp*RuCl(PN)

N

O

O

R NHR

O

OH

NR

O

O

NCH2Ph

O

O

EtMe

CH2PhPh

>99>99>99>99

R yield, %

NR

O

O

NCH2Ph

O

O

PhCH2Ph

4-NO2C6H4

4-MeOC6H4

>9988

>99>99

R yield, %

PhMe

3,4-Cl2C6H3

4-FC6H4

>99

>99>99

R yield, %

R

>99

n

10

32

>99>99>99>99

n yield, %

4 >99J. Am. Chem. Soc., 2007, 129, 290.

DEPROTECTION OF N-Phthaloyl AMINO ACID ESTER

N

O

O

CO2Me

R

Cp*RuCl(PN)KOt-Bu2-propanol80 °C, 2 h

Cl•H3N CO2Me

R

>99% yield

HCl

+ H2

10 atmHN

O

HO

CO2Me

R

1,4-dioxane30 °C, 1 h

O

O

+

>99% yield

J. Am. Chem. Soc., 2007, 129, 290.

+ H2 2-propanol80 ºC, 24 h

Cp*RuCl(PN)KOt-Bu

30 atm

NRAr

O

O

NHRAr

OH

O

Cp*RuCl(PN)

NAr

O

O

NAr

O

O

NAr

O

O64% ee 75% ee 85% ee

NAr

O

O3,4-: 88% ee2,4-: 88% ee

(OMe)2NAr

O

O2-: 89% ee4-: 91% ee

OMeNAr

O

OX = CH2: 90% eeX = O : 99% ee

X

X

Ru:KOt-Bu = 1:1 (10 mol%), [imide] = 0.20 MAr = 4-FC6H4

>99% yield

ASYMMETRIC HYDROGENATION WITH CHIRAL PN LIGAND

J. Am. Chem. Soc., 2007, 129, 290.

ASYMMETRIC SYNTHESIS OF PAROXETINE

J. Am. Chem. Soc., 2007, 129, 290.

NHAr4-FC6H4

OH

O

1) CBr4, PPh3NAr4-FC6H4

O

NH2Cl4-FC6H4

Ar = 3,4-(OCH2O)C6H3

Paroxetine (SSRI)

2) NaH

>99% ee

CO2Et

CO2Et

[RhCl(cod)]2NEt3dioxane aq.

4-FC6H4B(OH)2

CO2Et

CO2Et4-FC6H4 4-FC6H4

steps

O

O

NAr

2-propanol

H2 / Cp*RuCl(PN)

NH4-FC6H4

O

CAN

O

O

O

steps

R

APPLICABLE sym-CYCLIC IMIDES

+ H2 2-propanol80 ºC, 24 h

Cp*RuCl(PN)KOt-Bu

30 atm

Cp*RuCl(PN)Ru:KOt-Bu = 1:1 (10 mol%), [imide] = 0.20 MAr = (3,4-OCH2O)C6H3

NAr

O

O

NHAr

O

OH

Rn Rn

NAr

O

O91% ee

Cl

Cl

NAr

O

O96% ee

NAr

O

O94% ee

NAr

O

O94% ee

NAr

O

O97% ee

RuCl

Ph2P

NH

n

n = 1,2

92% ee

NAr

O

O91% ee

NAr

O

O

*

MOLECULAR STRUCTURES OF N-3,4-(OCH2O)C6H3 DERIVATIVES

FO

O

O

O

N

FO

O

O

N

P21(#4)R1(wR2)=0.048(0.121)

P212121(#19)R1(wR2)=0.043(0.123)

dihedral angle = 67.8 °

Co–workers

JSPS Kakenhi

Financial Support

Mr. Makoto HirakawaDr. Akihide Osaku Ms. Ayaka SakaguchiMs. Miho AshiaraiMr. Akira ShiibashiMr. Yuji ShibataMs. Chika KobayashiMr. Kentaro Yamaguchi

Kawakami Memorial Foundation

Ms. Mariko SugizawaDr. Sachiko Kitahara Mr. Kensuke YamamotoMs. Hiroko KomatsuMr. Yoshinori EndoMr. Masahiro YamamuraMs. Noriko Tejima

Taisho Pharmaceutical Co. Ltd

Prof. Shigeki Kuwata Prof. Takao Ikariya

ACKNOWLEDGEMENT

The Asahi Glass Foundation