1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal...

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Metal Hydrides Many different routes to metal hydrides: L n M H (H) L n M X M 2 H + transmetallation (M 2 = Sn, B, Si) L n M + H 2 oxidative addition protonation L n M + H + β-elimination ML n H β-elimination O L n M H O L n M H O HO L n M C O (insertion) Transition metal hydrides are important intermediates and show up in many different processes, such as hydrogenation, hydroformylation, and hydrometallation. Because of their facile generation (see below) they can often be a bit of a nuisance. Their reactivity can vary from hydride donors to strong protic acids.

Transcript of 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal...

Page 1: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Metal Hydrides

Many different routes to metal hydrides:

LnM H(H)

LnM X M2 H+

transmetallation(M2 = Sn, B, Si)

LnM + H2

oxidative addition

protonationLnM + H+

β-elimination

MLnH

β-elimination

OLnM

H

OLnMH

O

HO–

LnM C O

(insertion)

Transition metal hydrides are important intermediates and show up in many different processes, such as hydrogenation, hydroformylation, and hydrometallation. Because of their facile generation (see below) they can often be a bit of a nuisance. Their reactivity can vary from hydride donors to strong protic acids.

Page 2: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Common Homogeneous Hydrogenation Catalysts

Two classes of hydrogenation catalysts–monohydride and dihydride. Each have different mechanisms and different selectivities.

Homogeneous hydrogenation are usually carried out with catalysts based on Rh, Ru, and Ir. These complexes are more sensitive than heterogeneous catalysts (Pd/C), but are more selective. Also the presence of ligands around the metal allows for asymmetric hydrogenation.

Rh(H)(PPh3)3(CO): monohydride catalyst, specific for terminal alkenes, double bond isomerization competes, little used

Rh PPh3

H

COPh3PPh3P H2R+ RH

HR+

does not react with catalyst

The monohydride pathway is also important with Ru(II) asymmetric hydrogenations

RhCl(PPh3)3–Wilkinson's catalyst: dihydride catalyst, predictable olefin selectivities, no isomerization with neutral conditions

Cl Rh PPh3

PPh3

PPh3

H2R+ RHH

R≈ >

RR>

R

R

>R

R

>R R

R

R

R

R

R

Rdo not react

Page 3: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Ir

Common Homogeneous Hydrogenation Catalysts

Ir(cod)(PCy3)(Pyr)PF6–Crabtree's catalyst: at least 100 times more active than Wilkinson's catalyst, typically used with nopolar, noncoordinating solvents (CH2Cl2), dihydride mechanism

PCy3

NPF6

d8, 16e–

H2

CH2Cl2" Ir(PCy3)(pyr)(CH2Cl2) " = L2Ir(I)

d8, 12e–

(very unsaturated)

In the presence of H2, the cod ligand suffers hydrogenation, while the solvent may be loosely associated with the metal, it can be replaced by just about any olefin, including tri- and tetrasubstituted.

Cationic Rh catalysts are used as well and have a similar mechanism

Crabtree's cat.

Wilkinson's cat.

6400

650

4500

700

4000

0turnover frequency (h-1)

Page 4: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Homogeneous Hydrogenation ExamplesMe

OBz

O

Me

H

MeMe

OBz

O

Me

H

MeH2

RhCl(PPh3)3

90% yield

Org. Lett. 2000, 2, 2125.

O

Br Br

O

Br Br

4 mol%Crabtree cat.

94% yield

Tetrahedron Lett. 1981, 22, 303.

O

OMe

MeOTr

O

OMe

MeOTr

Me

H

H2RhCl(PPh3)3

80% yieldCan. J. Chem. 1978, 56, 2700.

R1 R

R2

OH

0,1Me

R1 R

R2

OH

0,1

H2 (1-3 atm)RhCl(PPh3)3

90% yieldR1 = H, Me 76-96% yield

>95:5 selectivityJ. Am. Chem. Soc. 2004, 126, 4130.

Page 5: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Directed HydrogenationsLewis basic groups (typically alcohols) in the allylic or homoallylic position can be used to direct the delivery of the hydrogenation from the same side, oftern with high diastereoselectivity. Cationic catalysts are usually employed.

Typical catalysts: [Ir(COD)pyr(PCy3)]PF6 [Rh(nbd)(dppe)]BF4 [Ir(COD)(dppb)]BF4

OH

ML

L H2

solventM

s

L s

L ML

O

L

R

HR

RH

OH

RR

R

OH

RR

L2M(COD)BF4

H2

Utility is in setting new stereocenters diastereoselectively

ML

O

L

R

H

HR

vs.

H2

MLL

R

H

OHH

RH

ML

O

LMe

R

H

RH

H

Me

OH

RR

Me H

Other Lewis basic sites can direct as well.

Page 6: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Directed Hydrogenation Examples

MeMe

MeO

MeMe

MeO

H2Crabtree's cat

99% yield

Me

HO i-Pr

Me

HO i-Pr

Me

HO i-Pr

CrabtreePd/C

>99.9%20%

<0.1%80%

O

CO2MeMe

H2Crabtree's cat

OMe

CO2MeMe

OH

Me

i-PrOH

Me

i-Pr

[Rh(nbd)(dppe)]BF4H2 (800 psi)

H70:1

NH

N

Me

O

O

NH

N

Me

O

OH2

Crabtree's cat

>99:1

Page 7: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Asymmetric HydrogenationsAsymmetric hydrogenation has matured into an incredibly imporant technique for bench chemists as well as industrial chemists. Very clean reactions, essentially no background reaction to introduce racemic material, often very low catalyst loading can be used with modern ligands.

PPh2

PPh2

RuCl2

OH

O

CO2H

Me

OH

O

CO2H

Mecat.H2 (X psi)

Et3N

MeOH (13.4L)

3.92 kg, 18.8 mol) 3.32 kg, 86% yield)97.3% ee

cat.76.4 g, 0.096 mol

0.005 mol%Org. Proc. Res. Dev. 2009, 13, 525–534.

Editorial: If a process chemist can make a chiral center by hydrogenation that will likely become the preferred route.

2001 Nobel Prize in Chemistry: 1/4 William S. Knowles, 1/4 Ryoji Noyori both for asymmetric hydrogenation technology

Where does current innovation take us? Many substrate types can be considered to be "solved problems", though others are still challenging. Many times this problem is "nothing more" than screening ligands.

Page 8: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Asymmetric Hydrogenations-Ligand SurveySome of the more commonly used phosphine ligands:

O

O

MeMe

PPh2

PPh2

(R,R)-DIOP

PPh2

PPh2

(R)-BINAP

PPh2

PPh2

(R)-H8-BINAP

PPh2

PPh2

(R)-SegPHOS

PPh2

PPh2

MeOMeO

(R)-MeO-BIPHEP

O

O

O

O

PP

Me

MeMe

Me

(R,R)-Me-DUPHOS

P P

Me

Me

Me

Me(R,R)-Me-BPE

Me

Me

PPh2

PPh2

(R,R)-CHIRAPHOS

PPh2

PPh2

(S)-PHANEPHOS

PPh2

PPh2

O

OO

O

(R)-SYNPHOS

PPt-But-Bu

H

H

(S,S,R,R)-TANGPHOS

Ph2PP(t-Bu)2

MeH

Fe

Josiphos-type

PPh2 N

O

t-Bu

(R)-t-BuPHOX

O

O

(R)-MonoPhos-type

P NR

R

Page 9: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Asymmetric Hydrogenations–The First Highly Selective ResultsThe first highly selective hydrogenation results:

CO2H

NHAc

MeO

AcO

CO2H

NH2

HO

HO

1) 0.05 mol% Rh(COD)(R,R-DIPAMP)BF4 3.5 atm H2, 88% i-PrOH, 50 ºC

2) HBr, H2OL-DOPAfirst step: 94% ee

R,R-DIPAMP:

P P PhPh

MeO

OMeKnowles (Monsanto): J. Am. Chem. Soc. 1975, 97, 2567 J. Am. Chem. Soc. 1977, 99, 5946

CO2H

NHAc

CO2H

NH2

cat. Rh(COD)(R,R-DIOP)ClH2, Et3N, benzene:EtOH (1:2)

95% yield, 72% optical purity

O

O

MeMe

PPh2

PPh2

R,R-DIOP: Kagan: J. Chem. Soc., Chem. Commun. 1971, 481

Page 10: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Asymmetric Hydrogenations–The First Highly Selective ResultsMechanism of acetamidopropenoates is best studied and illustrates the issues associated with selectivity. All other mechanisms we have discussed still hold. The chiral ligand means diastereomeric complexes can be formed, each with their own set of rate constants

NH

Ms

L s

L

ML

O

L

MeMeO2C

ML

O

L

OPh

+

Me Me

Ph Ph

NH

NH CO2MeMeO2C

diastereomers

H2

k1k-1 k'-1

k'1

k2 k'2H2(fast) (very slow)

minor (< 5%) major (> 95%)

ML

H

L

NH

MeO2CO

Me

PhH

ML

H

L

NH

CO2MeO

Me

PhH

MeO2C NHAc

Ph

CO2MeAcHN

Ph

(R) > 98% (S) < 2%

rapid equillibration of diastereomeric complexes

one diastereomerreacts much quicker with H2 than the other(Curtin-Hammett)

Page 11: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Asymmetric Hydrogenations-Some examples

NHAc

CO2Me

NHAc

CO2Me

Rh(cod)2BF4H2 (10 atm)

CH2Cl2100% conv.

99% eesubst:cat:L(100:1:2)

J. Am. Chem. Soc. 2002, 124, 14552.

O

OP N

Bn

Me

CN

CO2– tBuNH3+

Rh(cod)(ligand)BF4H2 (50 psi)

MeOH, rt, 40 h

CN

CO2– tBuNH3+

(S/C: 27000:1)

PPMe

(S)-trichickenfootphosJ. Am. Chem. Soc. 2004, 126, 5966.

Too many examples to make a representative list - best to search for similar system. Many cases need functional group to bind to metal

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Asymmetric Hydrogenations-Some examplesIridium is becoming important for isolated olefins

N

O

(COD)IrN

N

i-Pr

i-PrPhPh

Me

PhPh

Me

cat. I

0.6 mol% cat. IH2 (50 atm)

25 ºC, CH2Cl2

J. Am. Chem. Soc. 2003, 125, 113.98% ee

MeO

MeMe

MeO

MeMe

*

1 mol% [IrL1(cod)]BArF50 bar H2

CH2Cl2, 23 ºC

MeMe

MeMe

*

1 mol% [IrL2(cod)]BArF50 bar H2

CH2Cl2, 23 ºC92% ee

93% ee

NO

(o-Tol)2P

Ph

N

O(t-Bu)2P

PhL1 L2Science 2006, 311, 642.

Page 13: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Ru-Catalyzed Asymmetric HydrogenationsRuthenium catalysts are also quite useful, but proceed through a different mechanism. Useful for unsatruated acids, but other coordinating groups work as well. Thought to proceed through a "monohydride mechanism"

R2

R1

CO2H

R3

R2

R1

CO2H

R3

* *

Ru(OAc)2(binap)H2

MeOH

Ru

O

OO

OP

P

R

Ru

H

OO

SP

P

R3

R1

R2 R3 R2

R1

+ H2+ S

– RCO2HRu

S

O

SP

P R2

O

R3

H

R1

A

+ RCO2HA

Mechanism of olefin hydrogenation by LnRu(OAc)2

+ S

Insertion

Ruthenium remains in +2 oxidation state throughout the mechanism.

Page 14: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Noyori Asymmetric HydrogenationMost hydrogenation catalysts are selective for olefins over other potentially reduceable functional groups (ketones, aldehydes, esters, etc.). But halogen- or methallyl-containing Ru(+2) catalysts can reduce ketones, as long as there is a heteroatom in the α-, β-, or γ-position.

R

O

CnX

n = 1–3X = OH, OMe, NMe2, Br, COSMe, CONMe2, PO(OMe)2, SArCn = sp2, sp3

Ru(II)-BINAPH2

R

OH

CnX

*

reduction of β-ketoesters is illustrative of overall mechanism

+ H2

– HClA

(BINAP)RuCl2S2 (BINAP)RuHClS2R OR

O O

R

OR

O

ORuBINAPCl

Hinsertion+ H+

R

OR

O

ORuBINAPCl

HH

+ Sn

R OR

OH O

(BINAP)RuClSn

+ H2– H+

Page 15: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Noyori Asymmetric HydrogenationThe stereoselectivity can be rationalized by a "quadrant" model. This is a fairly general model that can be used in many metal-catalyzed reactions.

P Ru P

simplified X-raystructure of catalyst

Ru(OAc)2[(S)-BINAP] =

equitorial forward

axial back

only two quatrants are available for the ligand (substrate)

to occupy

PRu

P

O O

Cl

ORR

H

(R)-BINAP

R OR

OH O

PRu

P

OO

Cl

RO R

H

(S)-BINAP

R OR

OH O

(R)-β-hydroxy ester (S)-β-hydroxy ester

R-group in open quadrant

R-group in open quadrant

Page 16: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Noyori Asymmetric Hydrogenation-Examples

(R)-BINAP (S)-BINAPO

OEt

OBnO

H2 (4 atm)7.0 g [RuCl2(C6H6)]2

18.0 g (R)-BINAP

DMF/EtOH100 ºC, 12 hrs10.0 kg (42.3 mol)

OH

OEt

OBnO

9.7 kg96% yield, 97.1% ee

Synthesis 1995, 1014

in situ catalyst preparation

C5H11

O

OMe

OH2 (1 atm)

2 mol% Ru(methallyl)2(cod)2 mol% (S)-MeO-BIPHEP

acetone/aq. HBr then MeOH50 ºC, 5 hrs

C5H11

OH

OEt

O

100% yield97% ee

Tetrahedron Lett. 1995, 36, 4801

methallyl precursor allows for use of 1 atm H2

other binding groups possible as well. In this case a kinetic resolution.

Me

OOH

PhMe

OHOH

PhMe

OOH

Ph

H2 (100 atm)RuCl2[(R)-BINAP]

EtOH+

50.5%92% ee

49.5%92% ee

Page 17: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Noyori Dynamic Kinetic Asymmetric Hydrogenation

Racemic β-ketoesters – If the initial stereocenter present in the starting material can undergo rapid epimerization under the reaction conditions, a single diastereomer will be formed and with high ee.

Me

O

NHAc

O

OMe

H2 (100 atm)0.4 mol% RuBr2(R)-BINAP

CH2Cl2, 15 ºC, 50 hMe

OH

NHAc

O

OMe

99%, 98% eekS,R

kinv kinv

Me

O

NHAc

O

OMe

H2 (100 atm)0.4 mol% RuBr2(R)-BINAP

CH2Cl2, 15 ºC, 50 hMe

OH

NHAc

O

OMe

1%, >90% eekR,R

The stereoisomer of the alcohol is dependent on the ligand, but the configuration of the α-position is substrate dependent.

kinv > kS,R and kR,R

Page 18: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Noyori Dynamic Kinetic Asymmetric Hydrogenation

Me

O

Me

O

OEt

H2 (100 atm)RuBr2(R)-BINAP

Me

OH

Me

O

OEt Me

OH

Me

O

OEt

kinv < kS,R and kR,R

+

1 : 1

H2 (100 atm)RuCl2(R)-BINAP•C6H6

CH2Cl2, 50 ºCOMe

OO

OMe

OOH

OMe

OOH

H Hanti syn99:1

93% ee (R,R)

H2 (100 atm)RuCl2(R)-BINAP•C6H6

CH2Cl2, 50 ºCOMe

O O

OMe

OH O

OMe

OH O

syn anti99:1

J. Am. Chem. Soc. 1989, 111, 9134.J. Am. Chem. Soc. 1993, 115, 144.

Page 19: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Hydrogenation of "Unfunctionalized" KetonesBy combining a chiral diamine ligand with a chiral phosphine, the asymmetric hydrogenation of "unfunctionalized" (ketones without a second binding group) ketones can be acheived.

R1 R2

ORuCl2(S)-BINAP / dpen or daipen

H2, KOH or KOt-Bu, i-PrOH

R1 R2

OH Ph

NH2

NH2

Ph

(R,R)-dpenH2N

H2N

(R)-daipen

OMe

OMe

RuCl

Cl

NN

PP

H2–HCl

H H

H H

RuH

Cl

NN

PP

H H

H H

R1 R2

O

RuH

Cl

NN

PP

H H

H H

OR2

R1

activates C=O

Ru(II), 18 e–

RuCl

NN

PP

H

H H

Ru(II), 16 e–

H2RuCl

NN

PP

H

H H

HH

basic

nucleophilic

electrophilic

J. Am. Chem. Soc. 1998, 120, 13529.

J. Am. Chem. Soc. 2003, 125, 13490.

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Hydrogenation of "Unfunctionalized" Ketones

O RuCl2[(S)-xyl-BINAP][(S)-daipen]H2 (8 atm), K2CO3, i-PrOH, 96%

OH

95% ee

O trans-RuH(η1-BH4)[(S)-xyl-BINAP][(S,S)-dpen]H2 (8 atm), i-PrOH, no base

OH

95%, 99% eeJ. Am. Chem. Soc. 2002, 124, 6508.

RuCl2[(R)-BINAP][(S,S)-dpen]H2 (8 atm), KOH, i-PrOH

97%, 90% ee

OMe

Me Me

OHMe

Me Me

cyclopropanesurvives

C=C survives

RuCl2[(S)-BINAP][(R,R)-dpen]H2 (4 atm), KOH, i-PrOH

syn:anti 99.8:0.2, 93% ee

O OH

Page 21: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Asymmetric Transfer HydrogenationIn all previous examples, H2 served as the terminal reductant. The elements of H2 can come from other sources as well (isopropanol and formic acid).Meerwein-Ponndorf-Verley Reduction

R1 R2

O Al(Oi-Pr)3

i-PrOHO

H

OAl

i-PrO Oi-Pr

MeMe

R1R2

R1 R2

OH

Me Me

O+

Metal-catalyzed transfer hyrdogenation – Two mechanisms are possible

M(n)

RCH2O M(n)RCH2OH

HX

RCHO

H M(n)

O M(n)

HR

R

RCH2O M(n+2)

H

H M(n+2)

H

RCHO

O M(n+2)

HR

RH

H+

R

O

RR

O

R

B.E.

insertion

O.A.

X M(n)

RCH2OH

B.E.

insertion R.E.

Page 22: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Me

i-Pr

Asymmetric Transfer HydrogenationNoyori CATHy catalysts – Catalytic Asymmetric Transfer Hydrogenation

N

N

Ph

Ph

Ts

RuCl

Me

i-Pr

H Hcatalyst precursor

N

NH

Ph

Ph

Ts

Ru

amido complex(active catalyst)

KOH

CH2Cl2H2O

both complexes easy to prepare and are reasonably stable

HNH2N

PhPh

Ts(S,S)-TsDPEN ($$)

[RuCl2(η6-p-cymene)]2($$)

+

Et3N

i-PrOH80 ºC

Me

i-Pr

N

NH

Ph

Ph

Ts

Rui-PrOH

15 min

N

N

Ph

Ph

Ts

RuH

Me

i-Pr

H H

isolable, one diastereomer consistently forms, X-ray

active reducing agent for ketones

Angew. Chem. Int. Ed. 1997, 36, 285

Page 23: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Asymmetric Transfer Hydrogenation

N

N

Ph

Ph

Ts

RuH

Me

i-Pr

H H

NTsRu

N

Ph

Ph

i-Pr

Me

H

H

H

C

ORS

Ar RS

O

Ar RS

OHH

possible CH/π interaction

Chem. Asian J. 2006, 1-2, 102.

Ar R

O 0.5 mol% RuCl complex

5:2 HCO2H–Et3N

0.5 mol% [RuCl2(mesitylene)]21 mol% (S,S)-TsDPEN

2.5 mol% KOH, i-PrOHAr R

OH

72-98% eeJ. Am. Chem. Soc. 1995, 117, 7562.

Ar R

OH

90-99% eeJ. Am. Chem. Soc. 1996, 118, 2521.

Ar

OH

R

0. 2 mol% amido complex

acetoneracemic

Ar

OH

R Ar

O

R+

43-51% recovery93-98% ee

Angew. Chem. Int. Ed. 1997, 36, 288

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Asymmetric Transfer Hydrogenationsome other reductions

OH

RR

90-99% eeJ. Am. Chem. Soc. 1997, 119, 8738.

NHR

R77-95% ee

J. Am. Chem. Soc. 1996, 118, 4916.

(from imine)

O

Ph

Me

NHCbz98% ee

(R,R)-catalystOH

Ph

Me

NHCbz>99% ee

(S,S)-catalystOH

Ph

Me

NHCbz>99% ee

J. Am. Chem. Soc. 1997, 119, 8738.

Ar OEt

O O

NHBocracemic

[RuCl2(benzene)]2(S,S)-BnDPAE

HCO2H:Et3N (5:2) Ar OEt

OH O

NHBoc

69-95% yield32-98% ee

1 diastereomerPh

PhOH

NHBn(S,S)-BnDPAE

Org. Lett. 2010, 12, 5274.

Page 25: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Enone Reductions With Copper HydridesMuch like the selective reaction of alkyl cuprates with enones, copper hydrides with reduce enones through a 1,4-addition pathway.

Stryker's reagent – [(Ph3P)CuH]6: reduces double bond of conjugated ketones, aldehydes, esters, nitriles, and nitro compounds. stoichiometric reagent. E-enones reduced faster than Z-enones.

J. Am. Chem. Soc. 1988, 110, 291.

H

MeH

H

MOMO

O

H

MeH

H

MOMO

O

0.32 equiv[(Ph3P)CuH]6

C6H6, H2O

O

MeO 0.16 equiv

[(Ph3P)CuH]6

C6H6O

MeO

H

82% yield

85% yield16:1 dr

0.32 equiv[(Ph3P)CuH]6

TMSClC6H6

95% yield18:1 dr

Ph Me

TMSO

Ph Me

O

Page 26: 1-Metal Hydrides Introduction · PDF fileMetal Hydrides Many different routes to metal hydrides: L nMH (H) L nMX+M2H transmetallation (M2 = Sn, B, Si) L nM+ H 2 oxidative addition

Enone Reductions With Copper HydridesCatalytic methods have also been developed to address the atom economy of the process and to introduce asymmetry.

cat. [(Ph3P)CuH]6Bu3SnH or PhSiH3

PhCH3 (H2O), rt

O O

Tetrahedron Lett. 1998, 39, 4627.

5 mol% CuCl10 mol% (S)-p-tol-BINAP

5 mol% NaOt-Bu

4 equiv PMHS

Me

OEt

O

Me Me

Me

OEt

O

Me Me90% yield, 85% ee

Si O SiH

O Si

n

PMHS = polymethylhydrosiloxane

J. Am. Chem. Soc. 1999, 121, 9473.

0.1 mol% Ligand1 mol% Cu(OAc)2•H2O

PMHS, t-BuOH

PhCH3, rt

Org. Lett. 2008, 10, 289

EWG

R

EWG

RPPh2

PPh2Ligand

has been extened to other substrates