Redox Neutral Reactions

Wang Chao2011.3.12

Redox Economy and Redox Neutral Reactions:

Angew. Chem. Int. Ed. 2009, 48, 2854 – 2867

R OMe

OLiAlH4

R OHDess-Martin

DIBAL R H

O

RRu cat

H2/CO R

O

H

R

NEt2

R NEt2

(Z)

(E)R NEt2

R NEt2

(S,E)

(Z,E)

(S)-BINAP-Rh(I)

(S)-BINAP-Rh(I)

(R)-BINAP-Rh(I)

Developed by Noyori;Employed by Takasago in total synthesis of Menthol

R OR R OR

R NR2 R NR2

OH

HR

O

R

Redox Isomerization:

R

Br

H

O N-heterocycliccarbene

nucleophileR

Nu

O

H

O

Nu

Osame

R

O

R

OH

H

O

Nu

Osame

R R

Ph

Br

H

O

Ph

Br

O

N N

N

Ph

Ph

Br

OH

N N

N

Ph

Ph

OH

N N

N

Ph

N N

N

Ph

base

Ph

O

N N

N

Ph

PhNH2

Ph NHPh

O

Scheidt: J. AM. CHEM. SOC. 2009, 131, 18028–18029

Ph OAr

NH OP

NNNR Ar1

NHC

OH

ArO

NN

N

R

Ar1

OH

NN

N

R

Ar1

H

H

O

NN

N

R

Ar1

Ph

NHP

ArO

O

Ph

NP

addition;H-migration

eliminationC-C bondformation

acylation

H

ArO

O

H Ph

NP

+ NHC

Ph OAr

NH OP

Hydride Shift Reactions: transition metals, lewis acids, organocatalysis

Akiyama:J. Am. Chem. Soc. 2011, 133, 2424–2426

R3

EWGGWE

R2R1

HH

R1 = alkyl,R2 = H, R3 = alkyl or H

R1 = H,R2 = alkyl, R3 = alkyl

[1,5]-H shift

[1,6]-H shift

H

H

GWE EWG

EWGEWG

R1R3

R2

R3

CHO

N

DPPindole (1 eq.)

N

NH

W, 150oC,15min

Seidel:J. Am. Chem. Soc. 2011, 133, 2100–2103

recent examples:

H

O

Ph

[Rh(dppe)]2(BF4)2

PhOH

PhO

O

Ph

M = Rh

Rh

O

Ph

H M

H

Ph

O

+ PhOH- M

R

R

+O

R

Ru-catalyst R

R

R

O

R

R

+OH

R

Ru-catalyst R

R

R

OH

R

OH

R

O

H

NC ArKOH

RAr

CNR

Ar

CN

[O]

[H][IrCp*Cl2]2

R

OH

+NH2

R'

cat[IrCp*Cl2]2

R NH

R'

Borrowing Hydrogen: reduction and oxidation coupled

Adv. Synth. Catal. 2007, 349, 1555 – 1575

Breit: J. Am. Chem. Soc. 2011, 133, 2386–2389

R1

H[(COD)RhCl]2 / L

R2COOHR1

O

R2

O O

PPh2 PPh2

LCH-OxidationAlkyne Reduction

[Rh]

R2COOHa [Rh] OHa

OR2

R1

Hb

Hc

Hc

Ha

R1

Hb

[Rh]O

OR2

R1 O

O

R2·R1

H Ha/c

Ha/c

R2COOHa

[Rh] OHa/b

OR2

R1

Ha/b

Ha/c

Ha/c

[Rh]O

OR2

R1

Ha/b

Ha/c

Ha/cOO

R2 major product

minor product

R R

RR

RR

++

LnM LnMH2

cata

cata

metathesiscata'

R OH R O

R NR'R NHR'

LnM LnMH2

cata

cata

H2NR'-H2O

Alkane Metathesis Amine Alkylation

Transition metal mediated dehydrogenative activation

Chem. Rev. 2010, 110, 681–703

ROH

dehydrogenation

- 2H22 R

O

H

+ ROH

H

RO

OHR

HB:

-H2OR

OR hydrogenation

+ 2H2 ROH

R

Mechanism of the Guerbet Reaction:

Guerbet alcohols

OHdehydrogenation

- H2O

H

MLn

oxidativeaddition

O

MLnH

migratorydeinsertion

MLn

CO

H

reductiveelimination H

+ MLnCO

deactivated complex

Decarbonylation as a Potential Inhibiting Pathway in Alcohol Activation:

N-Alkylation of Amines by Alcohols:

R OHoxidation

reduction

R O

R NR'

R'NH2

H2O

2H

R NHR'amine

Alkylation of Activated Nucleophiles by Alcohols:

R OHoxidation

reduction

R O

R Nuc

Nuc:

H2O

2H

R Nuc

CNPh PPh3

O

RO NO2R NC

O O

OR

O

RO

N

O

N

O

O

NH

NC

O

O NH

O

Representative Activated Nucleophiles Employed in Alcohol Activation Reactions

OHPh

·

5 mol% Ir cat

5 mol% Cs2CO3

DCE:EtOAc (1:1)75oC, 15h

+

(1eq.)

(4 eq.)

OHPh

90% yield

OHPh 5 mol%[RuHCl(CO)(PPh3)3]

5 mol% dppfTHF, 95oC, 15h

+

OHPh

81% yield1:1 dr

Ph

Ph

Krische: Angew. Chem. Int. Ed. 2009, 48, 34–46 J. Am. Chem. Soc. 2007, 129, 15134. Angew. Chem., Int. Ed. 2008, 47, 5220. J. Am. Chem. Soc. 2008, 130, 14891.

Transfer Hydrogenative C-C Coupling:

OH

+

OAc

Allylation:

2.5 mol% [Ir(cod)Cl]2

5 mol% ligand10 mol% m-NO2BzOH20 mol% Cs2CO3

THF, 100oC, 20h

OH

76% yield86% ee

PPh2

PPh2

Cl

MeO

MeO

Clligand

R OH

R

OH

RO

LnIr

R O

HR

OH

IrH

RO

LnIr

OAc

HOAc

IrLn

R OHRO

H

LnIr

Hydroacylation:

Coupling of Primary Alcohols and Terminal Olefins via Hydroacylation:

MeO

OH

Bu+

5 mol%[Rh(coe)Cl]2

20 mol% P-Ligand100% mol% aminoPy4,4'-dipyridyl,phenol, 150oC, 6h

MeO

O

Bu

92%

COOH

Ph2PP-Ligand

N

H2N

aminoPy

OHR1OR1

oxidation imine formationNR1

N

hydroacylation R2

NR1

NR2

hydrolysisR2 R1

O

2HR2

R2

OH [M] O

alkene reacts withelectrophiles

alkene reacts withnucleophiles

OH

Cyclohexanone (10 mol%)Al(OtBu)3 (10 mol%)CH2Cl2, 100oC, 24h

MeCH(CN)2 (1 eq.)KO-t-Bu (1 eq.)

O

Me

CNNCO

Me

CN

CN

OH

Me

CN

CN

-H2 + H2

E+ Nu

Dihydride Mechanism:

Monohydride Mechanism:

R1 R2

OMLnH

H

-hydride elim.

M-H insertion R1 R2

O+ MLnH2

R3 R4

OMLn

H

R1 R2

OH

H

R3 R4

OH

H

R1 R2

OMLn

H

protontransfer

-hydride elim.

M-H insertion R1 R2

O+ MLnH1

Mechanism of activation of alcohol: