Hydrogenationheterogeneous

(catalytic)hydrogenation

g

homogeneous

oxidation state: Rh(I)valence electrons: 16e

Wilkinson’s catalyst catalyst for y yhydrogenation (1966)

Heterogeneous Pd Catalysts for Hydrogenation

大野桂二、佐治木弘尚, Organic Square (Wako) 2008, 22, 2.

Wilkinson’s catalyst RhCl(PPh3)3

R R R R R R

R R

RhCl(PPh3)3(cat )(cat.)

H2

CO2Me CO2Me CO2Me96% 4%

PtO2 or Pd/BaSO4(cat )

>49% 26%

(cat.)H2

Birch, A. J.; Williamson, D. H. Org. React. 1976, 24, 1.

Catalytic Cycle ◆dihydride◆hydrogen-first mechanism

RhL L

Cl LCl

H oxidativeRh

L S

Cl L

H2

H

R

H oxidative addition

reductive

L HH

LH

H

reductive elimination

RhL H

Cl LS

RhL

Cl LS

H

R

RhL H

H

i ti RCl L

R

insertionturnover-limiting step

Crabtree’s catalyst

TOF (h–1) of hydrogenationTOF (h ) of hydrogenation

Crabtree, R. Acc. Chem. Res. 1979, 12, 331.

mechanism: Ir(III) and Ir(V) rather than Ir(I) and Ir(III) ?Hall, M. B.; Burgess, K. Chem. Eur. J. 2005, 11, 6859.

TON = turnover number = moles of product / moles of catalystTOF = turnover frequency = TON / time

Directing EffectsOH, CO2Me, C=O, or OMe

Stork, G.; Kahne, D. E. J. Am. Chem. Soc. 1983, 105, 1072., ; , , ,

Crabtree, R. H.; Davis, M. W. J. Am. Chem. Soc. 1986, 51, 2655.

Catalytic Asymmetric HydrogenationH

Cy

PhCO2H

NHAc

H2RhBF4[((R)-camp)2(cod)] (cat.)

PhCO2H

NHAc (R)-CAMP

PMe

OM88% ee OMe

H2 O PPhPh

CO2H

NHAc

2RhCl[(R,R)-diop] (cat.)

PhCO2H

NHAc85% ee

(R,R)-DIOP

O

O PPh2

PPh2

85% ee

H2

PhCO2H

NHBz

[Rh((R)-binap)(MeOH)2]+ClO4– (cat.)

PhCO2H

NHBz100% ee

PPh2

PPh2

100% ee(R)-BINAP

「演習で学ぶ有機反応機構」化学同人 A019

CyNMe2

Akabori, S. et al. Nature 1956, 178, 323.

CAMP

PMe

OMePh

PMe

Bu

Horner et al (1968)

O

O PPh2

PPh2

DIOP

FePPh2

PPh2

BPPFACAMPKnowles, et al. (1972)

Horner, et al. (1968)Knowles, et al. (1968)

DIOPKagan, et al. (1971)

BPPFAHayashi, Kumada, et al. (1974)

Ph PC6H4-2-OMe

PPh2

PPh2

N

Ph2P

PPh

PPh2

PPh

P

PC6H4-2-OMe

Ph

BINAPNoyori, et al. (1980)

Boc PPh2

BPPMAchiwa (1976)

PPh2

chiraphosBosnich, et al. (1977)

Ph

DIPAMPKnowles, et al. (1975)

Catalytic Cycle◆dihydride P

Rh

Ph B'y

◆olefin-first mechanism RhPO

NRO2C

H

PhCO2R

NHAc PPhA

BP

RhP

SS

NHAc PRh

P ON

CO2R

HH

H2

PhCO2R

NHAc

turnover-limiting step

2

PPhH

P

Ph

CO RH C

D

RhP

O NCO2R

H

HP

RhP O N

CO2RH

S

Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley & Sons: New York, 1994.Cf.) For hydrogen-first mechanism in cationic Rh catalysis: Gridnev, I. D.; Imamoto, T. Acc. Chem. Res. 2004, 37, 633.

Curtin–Hammett Principle

Seeman, J. I. et al. J. Am. Chem. Soc. 1980, 102, 7741.

Enantioselective Isomerization

NEt27 tons

P

R RP

RR

Rh ClO4

P

R RP

RR

4

R = Me

NEt2

99% i ld

6.7 kg

99% yield98.5% eeTON = 8000

OH (–)-menthol

Tani, K.; Yamagata, S.; Akutagawa, S.; Kumobayashi, S.; Takemoto, T.; Takaya, H.; Miyashita, A.; Noyori, R.; Otsuka, S. J. Am. Chem. Soc. 1984, 106, 5208. 芥川進 有合化 1986, 44, 513.

Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley & Sons: New York, 1994.

◆monohydrideCatalytic Cycle

Morris, R. H. In Handbook of Homogeneous Hydrogenation; de Vries, J. G.; Elsevier, C. J., Eds.; Wiley-VCH: Weinheim, 2007.

Hydrogenation of Ketones

Enantioselective Hydrogenation

Kinetic Resolution

Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley & Sons: New York, 1994.

Dynamic Kinetic Resolution (DKR)

100% conversion, dr = 99:1, 92% ee

OMe

OO

OMe

OHO

OMe

OHO

+

major minor

OO OHO OHO

OMe OMe OMe+

Noyori, R. et al. J. Am. Chem. Soc. 1989, 111, 9134.

Route to a Key Intermediate of Carbapenem

O

OMe

O H2Ru(II)-cat.

OH

OMe

O 1) HCl2) NaOH

OH

OH

O

NHBz NHBz NH2

PPh

DKR

PPh3

OTBSTBSClimi.

RuCl3·nH2OAcO2HAcONa

OTBSOAc

NO H

NO H

Shimizu, H. et al. Acc. Chem. Res. 2007, 40, 1385.

BINAP/1,2-Diamine–Ru(II) Complex

OH2 (8 atm)

catalyst (0.2 mol%)

OH catalyst =

R2P Cl H2

N Ph

100% yield

PR2

Ru

Cl NH2

N

Ph

+ KOH

96% eeR = 4-tolyl

OO

H H

P

PRu

H

X N

H2N

P

PRu

X N

HN

X H2H2

X NH2

For mechanistic studies, see: Noyori, R. et al. J. Am. Chem. Soc. 2003, 125, 13490.Bergens, S. H. et al. J. Am. Chem. Soc. 2008, 130, 11979.

Asymmetric Transfer Hydrogenation

T

NPh

Ts

RuO OHN

H2Ph Cl

(0.5 mol %)KOH (0.6 mol%)

O OH

>99% yield97% ee

Noyori, R. et al. J. Am. Chem. Soc. 1997, 119, 8738.

97% ee2-propanol

28 °C

NPh

Ts

R

NH2

Ph

Ru

Cl

(0.1 mol %)HCO H / Et N

O OHHCO2H / Et3N

100% yielddl : meso = 98 6 : 1 4

DMF40 °CO OH

dl : meso = 98.6 : 1.4>99% ee

Ikariya, T. et al. Org. Lett. 1999, 1, 1119.