nickel and cobalt catalyzed asymmetric codimerisation of alkenes guillaume pelletier litterature...

Nickel and Cobalt catalyzed asymmetric codimerisation of alkenes

Guillaume Pelletier

Litterature meeting October 26th 2010

R1H

Ni, Rh, Pd, Co, Ru

cat. H*

Challenges in asymmetric catalysis

• Activation of stable molecules:Use of abundantly available, preferably neutral, starting materials and prochiral substrates

(Alkynes, alkenes, carbonyl compounds, CO, CO2, HCN, H2, N2)

• Efficiency and selectivity: High turnover frequencies (substrate/catalyst/time) High reagent-based chemo- regio- and stereoselectivities

• Large-scale synthesis: Ambient reaction conditions Post-reaction recovery of products Cost of metal/ligands

An example of a very efficient industrial catalytic process : Ziegler-Natta polymerisation

TiCl Cl

Cl Cl

L

M = Al, Li, Mg, Zn...L is an unspecified ligand

+ M-R' TiCl Cl

Cl

L

R'

"Active-Catalyst"

- M-Cl +R

TiCl Cl

Cl

L

R'

R

Carbo-metallation

TiCl Cl

Cl

L

+R

TiCl Cl

Cl

L

R'

R

R'

R

R

Carbo-metallation

TiCl Cl

Cl

L

R

R'

RRepeat "n"

times

TiCl Cl

Cl

L

R

R'

R

n-H or

reductive termination

Polymers(HDPE + others)

Britovsek, G. J. P.; Gibson, V. C.; Wass, D. F., Angew. Chem., Int. Ed. 1999, 38, 428-447.Corradini, P.; Guerra, G.; Cavallo, L., Acc. Chem. Res. 2004, 37, 231-241.

• “In 2010, the total volume of plastics, elastomers, and rubbers produced from alkenes with these catalysts worldwide exceeds 100 million metric tons. Together, these polymers represent the largest-volume commodity plastics as well as the largest-volume commodity chemicals in the world.”

Industrial ton-scaled cationic Nickel catalyzed process : SHOP (Shell)

Keim, W. Angew. Chem., Int. Ed. 1990, 27, 235. Wilke, W.; Bogdanović, B.; Hardt, P.; Heimbach, P.; Keim, W.; M. Kröner, M.; Oberkirch, W.; Tanaka, K.; Steinrücke, E.; Walter, D.; Zimmermann, H. Angew. Chem., Int. Ed.1966, 5, 151.

"Ni-H"

NiH

Hydrometallation

Ni

H

Ni

H

("Repeat manytimes")

n

Insertion

-olefins

-H elimination

Contemporary C-C bond formation using (asymmetric) catalysis with olefins

Metathesis (Grubbs/Shrock/Chauvin)

R1 R2Ni, W, Re, Ru, Mo

cat.

R1R2

(RCM, CM, ROM, ROMP, ADMET, Enyne)

Transfer Hydrogenation (Krische)

Reductive coupling (Montgomery/ Jamison)

Hydroformylation/Hydrocyanation/Hydrogenation/Cyclopropanation

Hydrovinylation (Wilke, Rajanbabu, Leitner)

R1 R2

H

O

R3

Ni(cod)2

Bu3P, BEt3

Toluene or THFR1

R2

R3

OH

PPh2

R1H

Ni, Rh, Pd, Co, Ru

cat.R1

H

*

*

(+)-NMDPP

R1 O

R2H

OH

R2

or

RuHCl(CO)(PPh3)3(p-anisyl)3P, m-NO2BzOH

Acetone, THF, 95 °C

R1

Me

OH

R2(Also with Ir, Rh + H2)* *

Contemporary C-C bond formation using (asymmetric) catalysis with olefins

Metathesis (Grubbs/Shrock/Chauvin)

R1 R2Ni, W, Re, Ru, Mo

cat.

R1R2

(RCM, CM, ROM, ROMP, ADMET, Enyne)

Transfer Hydrogenation (Krische)

Reductive coupling (Montgomery/ Jamison)

Hydroformylation/Hydrocyanation/Hydrogenation/Cyclopropanation

Hydrovinylation (Wilke, Rajanbabu, Leitner)

R1 R2

H

O

R3

Ni(cod)2Bu3P, BEt3

Toluene or THFR1

R2

R3

OH

PPh2

R1H

Ni, Rh, Pd, Co, Ru

cat.R1

H

*

*

(+)-NMDPP

R1 O

R2H

OH

R2

or

RuHCl(CO)(PPh3)3(p-anisyl)3P, m-NO2BzOH

Acetone, THF, 95 °C

R1

Me

OH

R2(Also with Ir, Rh + H2)* *

Challenges in catalytic hydrovinylation

R1H

Ni, Rh, Pd, Co, Ru

cat. H*

• Activation of stable olefins

• Regiochemical outcome (branched vs linear)

• Chemoselectivity outcome (Lewis basic groups, other olefins)

• Control of oligomerisation and isomerisation

• Enantioselectivity in the branched product

Importance of heterodimerisation reactions

Wilke, G. Angew. Chem., Int. Ed. 1988, 27, 185. RajanBabu, T. V. Chem. Rev. 2003, 103, 2845.RajanBabu, T. V. Synlett 2009, 853.

R1

X

Hydrovinylation

R1

X

*

*

*H

H

Me

Me Me

Me OH

OH

Pseudopterosin A-F

Me

Me O

OH

Me

MeOO

OH

Me

Ibuprofene(Advil , Motrin )

Naproxen(Aleve )

N

N

Me

Me

Me

H

O

O

HN

Me(+)-Phenserine

NH

Me

MeMe

N

NHOH

O

Me

Me

Me

Lyngbyatoxin A

Early studies on propylene homodimerisation(Dimersol)

• TON : 65’000 [Propylene/Ni] (0.0015 mol%)• Reaction proceeds in liquid propylene• With P(t-Bu)3 = HDPE, P(t-Bu)(i-Pr)2 = branched dimerisation,

P(n-Bu)3 = linear hexenes and methylpentenes.

• Catalysis can be stopped by adding NH3

NiBr

BrNi + PR3

EtAlCl2

-70 °CNi

PR3

Me

NiPR3

EtAlCl3

EtAlCl3

Me MeMe + isomers

C6H5Cl or DCM

Bogdanović, B.; Henc, B.; Löser, A.; Meister, B.; Pauling, H.; Wilke, G. Angew. Chem., Int. Ed. 1973, 12, 954.Bogdanović, B.; Spliethoff, B.; Wilke, G. Angew. Chem., Int. Ed. 1980, 19, 622.Wilke, G. Angew. Chem., Int. Ed. 1988, 27, 185.

Early studies on propylene homodimerisation

.Wilke, G. Angew. Chem., Int. Ed. 1988, 27, 185.

Other pioneering systemsPh

(Reactive olefin)

Metal catalyst

ethylene (x atm), Temp.

Ph Ph

C6 olefins

ConditionsSelectivity for

major product (%)Yield (%) Comments

PPh3

Ph3PNi

Br

Ar (6 mol%)

BF3OEt2, >1 atm C2H4 0 °C, DCM

PBn3

Bn3PNi

NCMe

Ar(0.2 mol%)

BF4

25 °C, 1-2 h, 15 atm C2H4

[Ni(MeCN)6]2+ 2BF4- (1 to 0.5 mol%)

10 atm C2H4, Et2AlCl 20 mol%,

PPh3 or dppe 4 mol%, DCM, 25 °C

PdP

O OEt

PhPh

(0.1 mol%)

BF4

15 °C, 1h, DCM, 15 atm C2H5

91 67

94 94

87 98

41 91

Moderate selectivityand yields

Styrene dimerisation

Exothermic ethylenepolymerisation

Tolerant to Cl and MeOgroups

Tolerance to Lewis basicgroups variable on Ni/Al

and order of addition

Selectivity is 9% when100% conversion.

.Kawata, N.; Maruya, K.; Mizoroki, T.; Ozaki, A. Bull. Chem. Soc. Jpn. 1971, 44, 3217.


(Reactive olefin)

Metal catalyst


Ph Ph

C6 olefins



PPh3

Ph3PNi

Br

Ar (6 mol%)


PBn3

Bn3PNi

NCMe

Ar(0.2 mol%)

BF4

25 °C, 1-2 h, 15 atm C2H4

[Ni(MeCN)6]2+ 2BF4- (1 to 0.5 mol%)



PdP

O OEt

PhPh

(0.1 mol%)

BF4

15 °C, 1h, DCM, 15 atm C2H5

91 67

94 94

87 98

41 91








.Muller, G.; Ordinas, J. I. J. Mol. Catal., A : Chem. 1997, 125, 97.


(Reactive olefin)

Metal catalyst


Ph Ph

C6 olefins



PPh3

Ph3PNi

Br

Ar (6 mol%)


PBn3

Bn3PNi

NCMe

Ar(0.2 mol%)

BF4

25 °C, 1-2 h, 15 atm C2H4

[Ni(MeCN)6]2+ 2BF4- (1 to 0.5 mol%)



PdP

O OEt

PhPh

(0.1 mol%)

BF4

15 °C, 1h, DCM, 15 atm C2H5

91 67

94 94

87 98

41 91








.Fassina, V.; Ramminger, C.; Seferin, M.; Monteiro, A. L. Tetrahedron 2000, 56, 7403.


(Reactive olefin)

Metal catalyst


Ph Ph

C6 olefins



PPh3

Ph3PNi

Br

Ar (6 mol%)


PBn3

Bn3PNi

NCMe

Ar(0.2 mol%)

BF4

25 °C, 1-2 h, 15 atm C2H4

[Ni(MeCN)6]2+ 2BF4- (1 to 0.5 mol%)



PdP

O OEt

PhPh

(0.1 mol%)

BF4

15 °C, 1h, DCM, 15 atm C2H5

91 67

94 94

87 98

41 91








.Britovsek, G. J. P.; Keim, W.; Mecking, S.; Sainz, D.; Wagner, T. J. Chem. Soc., Chem. Commun. 1993, 1632

One of the most efficient system : Wilke’s chiral azaphospholane

• Can be applied to 4-Cl-, 4-isobutyl-, 2-methylstyrene, and 2-methoxy-6-vinylnaphtalene.

• Lewis basic functionalities are not tolerated• Only the (R,R)-azaphospholane give high ee values, yields.• Modification of the ligand corresponds to drastic drop of

stereoselectivity.• Et3Al2Cl3 is highly pyroforic.

Wilke, G. Angew. Chem., Int. Ed. 1988, 27, 185. Wilke, G.; Monkiewciz, J.; Kuhn, H., US Patent, 4912274, 1990.

NiCl

ClNi

(1 atm)

(0.05 mol%)

Et3Al2Cl3 (0.15 mol%)PR3* (0.05 mol%)

-60 °C, 2.5 h, DCM 97% yield, 93% ee

NiCl

ClNi

(1 atm)

(1.2 mol%)

Et3Al2Cl3 (1.2 mol%)PR3* (1.2 mol%)

-70 °C, 2.5 h, DCM 35% yield, 92% ee

P

NMe

H Ph

MeP

NMe

HPhMe

One of the most efficient system : Wilke’s chiral azaphospholane

• Can be applied to 4-Cl-, 4-isobutyl-, 2-methylstyrene, and 2-methoxy-6-vinylnaphtalene.

• Lewis basic functionalities are not tolerated• Only the (R,R)-azaphospholane give high ee values, yields.• Modification of the ligand corresponds to drastic drop of

stereoselectivity.• Et3Al2Cl3 is highly pyroforic.

Wilke, G. Angew. Chem., Int. Ed. 1988, 27, 185. Wilke, G.; Monkiewciz, J.; Kuhn, H., US Patent, 4912274, 1990.

NiCl

ClNi

(1 atm)

(0.05 mol%)

Et3Al2Cl3 (0.15 mol%)PR3* (0.05 mol%)

-60 °C, 2.5 h, DCM 97% yield, 93% ee

NiCl

ClNi

(1 atm)

(1.2 mol%)

Et3Al2Cl3 (1.2 mol%)PR3* (1.2 mol%)

-70 °C, 2.5 h, DCM 35% yield, 92% ee

Facts on Nickel catalyzed hydrovinylation

• Diminished reactivity of electron-deficient vinyl arenes

• The apparent poor reactivity of substrates carrying heteroatoms when R2Al-X Lewis acids are employed that could be the result of coordination of these atoms to aluminium

• The desactivating effect of coordinating solvents (DCM<C6H5F<C6H5Cl<toluene<nitrobenzene<Et2O)

• The isomerisation of the initially formed 3-arylbut-1-ene to

2-arylbut-2-ene

• The total inhibition of the reaction by strong σ-chelating phosphines (or bisphosphines) Kawata, N.; Maruya, K.; Mizoroki, T.; Ozaki, A. Bull. Chem. Soc. Jpn. 1974, 47, 413.

Müller, U.; Keim, W.; Krüger, C.; Betz, P. Angew. Chem., Int. Ed. 1989, 28, 1011.Nomura, N.; Jin, J.; Park, H.; RajanBabu, T. V. J. Am. Chem. Soc. 1998, 120, 459.

(50 atm)

Ni(cod)2 (0.02 mol%)

L (0.02 mol%), Tol., 50 °C

Oligomerization(C4-C30)

OH

PPh2

F3C

F3CL =

Ni(cod)2

OH

PPh2

F3C

F3CPCy3, toluene

10 °C

O

P

F3C

F3C Ni

Ph Ph

PCy3

H

Ni(cod)2

OH

PPh2

F3C

F3C

i) ethylene, toluene-20 °C

ii) PCy3, -20 °C

O

P

F3C

F3C Ni

Ph Ph

PCy3 20 °C

-ethylene

A

A

Possible implication of a nickel hydride intermediate

Müller, U.; Keim, W.; Krüger, C.; Betz, P. Angew. Chem., Int. Ed. 1989, 28, 1011.

Proposed catalytic cycle (Part 1)

NiX

XNi

X = Br, Cl

PR3Ni

X

PR3

16 é complex(no coordination site)

Lewis acidNi

PR3

Y

14 é complex

Y = Lewis acid/Xcomplex

R

NiPR3

RNi

PR3

R

NiPR3

Y YY

H H

NiPR3

H

Y

Active catalyst

Nomura, N.; Jin, J.; Park, H.; RajanBabu, T. V. J. Am. Chem. Soc. 1998, 120, 459.RajanBabu, T. V. Chem. Rev. 2003, 103, 2845.

Proposed catalytic cycle (Part 2)

Nomura, N.; Jin, J.; Park, H.; RajanBabu, T. V. J. Am. Chem. Soc. 1998, 120, 459.RajanBabu, T. V. Chem. Rev. 2003, 103, 2845.

Me NiPR3

Y*NiPR3

Y

Me

Ph

NiPR3

H

Y

Active catalyst

Ph

NiPR3Me

Y

NiPR3

Y

Me

*

Me

*

Me

*

• Vary the ligands (phosphine)

• Replace the highly pyroforic Lewis acid in the previous catalytic cycle

• Use of silver salts or Brønsted acids with dissociated counter-ion

• Solvent effect (Lewis basicity…)

• Alternate metals? (Pd, Rh, Ru, Co…)

New propositions for the improvement of hydrovinylation reactions

PdCl

ClPd

PR3Pd

Cl

PR3

EtMgBr

Et2O

PdMe

PR3

Et2OH+BF4-

PdOEt2

PR3

BF4

DiRenzo, G. M.; White, P. S.; Brookhart, M. J. Am. Chem. Soc. 1996, 118, 6225.Nomura, N.; Jin, J.; Park, H.; RajanBabu, T. V. J. Am. Chem. Soc. 1998, 120, 459.RajanBabu, T. V.; Nomura, N.; Jin, J.; Nandi, M.; Park, H.; Sun, Y. J. Org. Chem. 2003, 68, 8431.

First efficient and «azaphosphalene-free » Ni-catalyzed heterodimerisation with ethylene

0.35 mol%[(allyl)NiBr]2/PPh3/AgOTf

DCM, -56 °C, 2 h(1 atm)

RR

Me

MeO Cl

Br Ph

F

MeO

>95% >95% >95% 81%

>95%

100% Selectivity

>95% 90% 90%

88%

Nomura, N.; Jin, J.; Park, H.; RajanBabu, T. V. J. Am. Chem. Soc. 1998, 120, 459.RajanBabu, T. V.; Nomura, N.; Jin, J.; Nandi, M.; Park, H.; Sun, Y. J. Org. Chem. 2003, 68, 8431.

First efficient and «azaphosphalene-free » Ni-catalyzed heterodimerisation with propene

Me[(allyl)NiBr]2 1.5 mol%

PPh3, AgOTf, DCMTemperature, Time

A B

Entry R Temp (°C) Time (min) Yield (%) Ratio (A:B)

1

2

3

4

5

6

7

8

RR R

i-Bu

OMe

Bz

NTs2

MVN

-15

-15

0

0

-40

10

10

-5

15

60

15

10

30

15

20

60

96

86

94

95

98

94

92

88

3:1

4:1

4:1

4:1

5:1

4:1

2:1

10:1

Cl

Br

OAc

Jin, J.; RajanBabu, T. V. Tetrahedron 2000, 56, 2145.

First efficient and «azaphosphalene-free » Ni-catalyzed heterodimerisation with norbornene

Kumareswaran, R.; Nandi, N.; RajanBabu, T. V. Org. Lett. 2003, 5, 4345.Park, H.; Kumareswaran, R.; RajanBabu, T. V. Tetrahedron 2005, 61, 6352.

"PR3-Ni-H"

+norbornene

+ethylene

Ni

PR3

NiL

PR3

"PR3-Ni-H"

(>99% Yield andSelectivity when

PR3 = PCy3)

Ni

PR3

+ethylene Ni

PR3

NiL

PR3

"PR3-Ni-H"

(>97% Yield andSelectivity when

PR3 = PPh3)

Possible asymmetric version of the heterodimerisation? 0.35 mol%

[(allyl)NiBr]2/AgOTfDiphosphine

DCM, -56 °C, 2 h(1 atm)

No reaction

PPh2Ph2PPPh2

PPh2O

OMe

Me

PPh2

PPh2N

CO2t-Bu

Ph2P

PPh2

BPPM (Achiwa)DIOP (Kagan)BINAP (Noyori)DPPP

PdI

IPd

*PR3Pd

I

*PR3

AgX

X = PF6 or SbF6

Pd*PR3

X

Pt-Bu O(-)-menthylP

Cy Ph

Ph

(10 atm)

[(allyl)PdI]2 0.2 mol%

AgSbF6, P*, 20 mL CH2Cl23 mL EtOAc(20 mL)

Ph *

+

Ph

79% yield84% Selectivity

86% ee

Possible asymmetric version of the heterodimerisation?

Bayersdörfer, R.; Ganter, B.; Englert, U.; Keim, W.; Vogt, D. J. Organomet. Chem. 1998, 552, 187.

0.35 mol%[(allyl)NiBr]2/AgOTf

Diphosphine

DCM, -56 °C, 2 h(1 atm)

No reaction

PPh2Ph2PPPh2

PPh2O

OMe

Me

PPh2

PPh2N

CO2t-Bu

Ph2P

PPh2

BPPM (Achiwa)DIOP (Kagan)BINAP (Noyori)DPPP

PdI

IPd

*PR3Pd

I

*PR3

AgX

X = PF6 or SbF6

Pd*PR3

X

Pt-Bu

PhO(-)-menthylP

CyBn

Ph

Ph

(10 atm)

[(allyl)PdI]2 0.2 mol%

AgSbF6, P*, 20 mL CH2Cl23 mL EtOAc(20 mL)

Ph *

+

Ph

79% yield84% Selectivity

86% ee

Use of hemilabile ligands for the asymmetric version of the heterodimerization

NiX

XNi

X = Br, Cl

NiX

P

16 é complex(no coordination site)

Lewis acidNi

P

16 é complex

Y = Lewis acid/Xcomplex

R

NiP

R

NiP

Y

H H

Active catalyst

P Z

Z

ZY

Z

If Z = PR3

not in equilibrium

ZY

NiP

HZ

Y

Nomura, N.; Jin, J.; Park, H.; RajanBabu, T. V. J. Am. Chem. Soc. 1998, 120, 459.RajanBabu, T. V.; Nomura, N.; Jin, J.; Nandi, M.; Park, H.; Sun, Y. J. Org. Chem. 2003, 68, 8431.


Nomura, N.; Jin, J.; Park, H.; RajanBabu, T. V. J. Am. Chem. Soc. 1998, 120, 459.Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J. Org. Chem. 1993, 58, 1945.RajanBabu, T. V.; Nomura, N.; Jin, J.; Radetich, B.; Park, H.; Nandy, M. Chem. Eur. J. 1999, 5, 1693.

MeO(1 atm)(MVN)

0.7 mol% [(allyl)NiBr]2

M-X, (S)-MOP, DCMMeO

OMe

PPh2

AgOTf

24% Yield>99% Selectivity

58% ee

OMe

PPh2

NaBARF

>98% Yield>99% Selectivity

62% ee

BARF = -B[(3,5-CF3)C6H3]4

OBn

PPh2

NaBARF


80% ee

PPh2

NaBARF


3% ee


Nomura, N.; Jin, J.; Park, H.; RajanBabu, T. V. J. Am. Chem. Soc. 1998, 120, 459.Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J. Org. Chem. 1993, 58, 1945.RajanBabu, T. V.; Nomura, N.; Jin, J.; Radetich, B.; Park, H.; Nandy, M. Chem. Eur. J. 1999, 5, 1693

MeO(1 atm)(MVN)

0.7 mol% [(allyl)NiBr]2

M-X, (S)-MOP, DCMMeO

OMe

PPh2

AgOTf


58% ee

OMe

PPh2

NaBARF

>98% Yield>99% Selectivity

62% ee

BARF = -B[(3,5-CF3)C6H3]4

OBn

PPh2

NaBARF


80% ee

PPh2

NaBARF


3% ee

A working hypothetical TS for the addition of nickel hydride to the vinyl arene

RajanBabu,T.V .; Nomura, N.; Jin, J.; Nandi, M.; Park, H.; Sun, X. J. Org. Chem. 2003, 68, 8431.Josef, J.; RajanBabu, T. V.; Jemmis, E. D. Organometallics 2009, 28, 3552.

Is the hemilabile ligation hypothesis a viable theory?• Minimalist construction of a hemilable model based

on chiral Me-DuPhos was necessary to probe the reactivity/selectivity of hydrovinylation.

Nandi, M.; Jin, J.; RajanBabu, T. V. J. Am. Chem. Soc. 1999, 121, 9899.Burk, M. J.; Feaster, J. E.; Harlow, R. L. Tetrahedron: Asymmetry 1991, 2, 569.

P

P

(S,S)-MeDuPhos

P

R

R

Size of thegroup

Tunabletether

Hemilabileatom

P NiO

RH

cis-olefin/P-complex

vs P NiO

RH

Ar

H

Effect of additional chiral centers

trans-olefin/P-complex

vs

Ar

HP Ni

OR

HH

Ar

Synthesis of various chiral phospholanes

X

Br

HP(O)(OEt)2, Pd(OAc)2, dppbDIEPA/DMSO

100 °C, 12 h

X

P

O

OEtOEt

X

PH2

LAH, Et2O

3 h, reflux

OOS

O O

KH, THF, 6 h

X

P

Me

Me

P

H

Me

Me

P

OBn

Me

Me

P

Me

Me

P

Me

Me

OBn OMe

Nandi, M.; Jin, J.; RajanBabu, T. V. J. Am. Chem. Soc. 1999, 121, 9899.

Synthesis of various chiral phospholanes


X

Br

HP(O)(OEt)2, Pd(OAc)2, dppbDIEPA/DMSO

100 °C, 12 h

X

P

O

OEtOEt

X

PH2

LAH, Et2O

3 h, reflux

OOS

O O

KH, THF, 6 h

X

P

Me

Me

P

H

Me

Me

P

OBn

Me

Me

P

Me

Me

P

Me

Me

OBn OMe

A B

Effect of counterions and hemilability « potential »


P

H

Me

Me

P

Me

Me

OBn

A B

Ph

[(allyl)NiBr]2 0.75 mol%Phosphine

Additive, CH2Cl2, -45 °C(1 atm) Ph *

vs

Entry AdditiveYield with

A (%)Yield with

B (%)Comments

1

2

3

4

5

AgOTf

AgClO4

AgNTf2

AgSbF6

NaBARF

94

95

<2

<2

<2

<2

<2

48

94

97

37% ee with A

37% ee with A

48% ee with B

50% ee with B

47% ee with B9% isomerisation

Hemilabile ligands containing a chiral 1,3-dioxolane

Zhang, A.; RajanBabu, T. V. Org. Lett. 2004, 6, 1515.


NaBARF, CH2Cl2, -45 °C(1 atm)

*

Ligand Conversion (%) Selectivity (%) ee (%)

P

OBn

R

R

P

St-Bu

Me

Me

P

Me

Me

O

O

R = Et

R = i-Bu

0 0 0

0 0 0

>95 >95 67

>95 >95 85

Hemilabile ligands containing a chiral 1,3-dioxolane



NaBARF, CH2Cl2, -45 °C(1 atm)

*

Ligand Conversion (%) Selectivity (%) ee (%)

P

R

R = Me

R = Et

>99 90 71

83 >95 88

>95 >95 91

>95 >95 90

O

O

P

O

O

P

O

O

Application of the hemilabile ligand in total synthesis


[(allyl)NiBr]2 0.70 mol%NaBARF, CH2Cl2, -55 °C, 2 h

Phosphine(1 atm)

MeMe

P

O

O

>99, 87% ee

1) 9-BBN (1.2 equiv)THF, 0 °C to rt

Pd(PPh3)4, K3PO4, 60 °CTHF/Dioxane, 14 h

Br2)

Me

55% over 2 steps(R)-(-)-Curcumene

Me

87% ee

1) HB(Siam)2, THF0 °C to rt

2) NaOH, H2O2

0 °C to rt Me

OH

Me

O

1) Swern oxidation2) THF, -78 °C to rt

3) Swern oxidation

BrMg

84%31% over 3 steps

(R)-(-)-ar-tumerone

Is the modified chiral MeDuPhos catalyst a better system?


[(allyl)NiBr]2 0.70 mol%NaBARF, CH2Cl2, -55 °C, 2 h

Phosphine(1 atm)

P

O

O

R

R

>100% Selectivity>95% yield

88% ee 87% ee 71% ee

73% ee 73% ee

MeOMeO

Me Br

Sugar phosphinite ligands used in hydrovinylation

[(allyl)NiBr]2 0.7 mol%NaBAr4, DCM

-50 °C or -70 °C

Diarylphosphinite L*(1 atm)

*

OPAr2

O

O

O

O

O

Ar2PO

OO

OPh

OMeNHAc

OAr2P

OO

OPh

OBnNH

OAc

Ar2P

OO

OPh

OBnNH

OTFA

Ar2P

OO

OPh

OBnNH

OBz

Ar2P

98% Conversion86% Yield

86% Selectivity<5% ee


99% Selectivity29% ee









Ar = 3,5-(CF3)2C6H3 Ar = 3,5-(CF3)2C6H3 Ar = 3,5-Me2C6H3

Ar = 3,5-Me2C6H3Ar = 3,5-Me2C6H3Ar = 3,5-Me2C6H3

Park, H.; RajanBabu, T. V. J. Am. Chem. Soc. 2002, 124, 734.Park, H.; Kumareswaran, R.; RajanBabu, T. V. Tetrahedron 2005, 6352.

Sugar phosphinite ligands used in hydrovinylation


[(allyl)NiBr]2 0.7 mol%NaBAr4, DCM

-50 °C or -70 °C


*

OPAr2

O

O

O

O

O

Ar2PO

OO

OPh

OMeNHAc

OAr2P

OO

OPh

OBnNH

OAc

Ar2P

OO

OPh

OBnNH

OTFA

Ar2P

OO

OPh

OBnNH

OBz

Ar2P


86% Selectivity<5% ee











Ar = 3,5-(CF3)2C6H3 Ar = 3,5-(CF3)2C6H3 Ar = 3,5-Me2C6H3

Ar = 3,5-Me2C6H3Ar = 3,5-Me2C6H3Ar = 3,5-Me2C6H3

Synthesis of enantioenriched (R)-Ibuprofene


[(allyl)NiBr]2 (0.7 mol%)AgSbF6, DCM, -70 °C


OO

OPh

OBnNH

OAc

Ar2P

Ar = 3,5-Me2C6H3

Br


89% ee

Br

NiCl2(dppp) (1.6 mol%)

i-BuMgCl

95%

O

O3, MeOHthen DMS

96%

OHO

KMnO4, Acetone

(R)-Ibuprofene66%

(-)-mentholDCC, DMAP

O(-)-menthyl-O

89% ee byGC analysis

Leitner’s study with Feringa phosphoramidite ligands

Franciό, G.; Faraone, F.; Leitner, W. J. Am. Chem. Soc. 2002, 124, 736.Hölscher, M.; Franciό, G.; Leitner, W. Organometallics 2004, 23, 5606.

Br

Cl

28.4% Conv.28.4% Selectivity

67.7% ee

83.4% Conv.98.8% Selectivity

91.9% ee

100% Conv.81.2% Selectivity

90.8% ee

(variable pressure)

[(allyl)NiCl]2NaBARF, DCM

TemperatureLigand

*

LigandQty Ligand

(mol%)Temp. (°C)

Selectivity (%) ee (%)Conv. (%)

N

Bu

PO

O

MeO

N

Bu

PO

O

Cl

N

Bu

PO

O

Cl

MeN

Ph

PO

O

Ph

Me

0.35

0.33

0.33

0.160.0210.00750.075

-30

-32

-32

-70-650

-50

13

100

33

1008910099.5

93.3

0%

96.2

84.910078.199.1

56.4

0% (Polym.)

87.2

94.891.176.289.7

Phosphoramidite screening and scope expansion done by RajanBabu

Smith, C. R.; RajanBabu, T. V. Org. Lett. 2008, 10, 1657.

O

O

P N

Ph

Ph

O

O

P N

Ph

Ph

O

O

P N

Ph

MeO (1 atm)

[(allyl)NiBr]2 0.7 mol%NaBF4, CH2Cl2, -78 °C

PhosphoramiditeMeO

*

O

O

P N

Ph

O

O

P N

Ph

Ph O

O

P N

Ph

PhO

O

P N

1-naphthyl

Ph

>99% Conv.>99% Selec.

94% ee


94% eeNo reaction

21% Conv.>99% Selec.

90% ee

14% Conv.>99% Selec.

16% ee

2% Conv.>99% Selec.

86% ee


98% ee

Phosphoramidite screening and scope expansion done by RajanBabu

Smith, C. R.; RajanBabu, T. V. Org. Lett. 2008, 10, 1657.Smith, C. R.; RajanBabu, T. V. J. Org. Chem. 2009, 74, 3066.

(1 atm)[(allyl)NiBr]2 0.7 mol%NaBF4, CH2Cl2, -78 °C

*

O

OP N

Ph

1-naphthyl

R R

MeO i-Bu Ph

MeO

F

PhO


97% ee


96% ee


97% ee


99% ee


97% ee

• DCM was added to a purged Schlenk flask with N2, and put in the glove-box.

• Mix [(allyl)NiBr]2, phosphoramidite and NaBARF in Schlenk. Stir for 2 hrs at rt.

• Suspension is filtered on a celite pad and transferred to another Schlenk flask and tanken out of glove-box.

• To another flamed dried flask, add DCM and transfer pre-catalyst dropwise at rt. Cool this solution at -70 °C.

• Purge with ethylene. Add the styrene derivative dropwise in DCM. Re-purge with ethylene and react for 4-6 hrs.

• Quench by adding to pentane and filter on silica gel plug.

Typical procedure for the hydrovinylation of styrene derivatives

Smith, C. R.; Zhang, A.; Mans, D.; RajanBabu, T. V. Org. Synth. 2008, 85, 238.

Enantioselective formation of quaternary carbon centers by hydrovinylation

Zhang, A.; RajanBabu, T. V. J. Am. Chem. Soc. 2006, 126, 5620.Shi, W.-J.; Zhang, Q.; Xie, J.-H.; Zhu, S.-F.; Hou, G.-H.; Zhou, Q.-L. J. Am. Chem. Soc. 2006, 2780.Smith, C. R.; Lim, H. J.; Zhang, A.; RajanBabu, T. V. Synthesis 2009, 2089.

OO

P

NPh

Ph

Yields 76% to 96%Selectivity 84% to 89%

ee 70% to 99%

(1 atm)[(allyl)NiBr]2 1.0 mol%NaBF4, CH2Cl2, -70 °C

O

OP N

Ph

Ph

R R

Me


95% ee

R'

Me

R'

Me


90% ee

Me

Me

90% Yield95% Selectivity

90% ee

Cl

Me


95% ee

Me


50% ee

Me


93% ee

Me

70% Yield71% Selectivity

95% ee

In comparison…

Takemoto, T.; Sodeoka, M.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1994, 115, 8477Hulme, A. N.; Henry, S. S.; Meyers, A. I. J. Org. Chem. 1995, 60, 1265.Fadel, A.; Azrel, P. Tetrahedron: Asymmetry 1997, 8, 371.

HON Me

Me

H

(+)-eptacozine

HOMe

H

N Me

(+)-aphanorphine

MeO

Shibasaki

Meyers

Me

MeO OTf

Me

OTBDPSAsymmetric Heck reaction

(93% ee)

MeO

NO

i-Pr

Stoichiometric oxazoline alkylation(99% ee)

Enzyme mediated desymmetrisation of chiral malonate (97% ee)

MeOMe

CO2Me

CO2Me

Catalytic hydrovinylation of 1,3-dienes

Zhang, A.; RajanBabu, T. V. J. Am. Chem. Soc. 2006, 128, 54.Buono, G.; Siv, C.; Peiffer, G.; Triantaphylides, C.; Denis, P.; Mortreux, A.; Petit, F. J. Org. Chem. 1985, 50, 1781.RajanBabu, T. V. Synlett 2009, 853.

t-Bu[(allyl)NiBr]2 7.0 mol%

PPh3, AgOTf

-56 °C, DCM(1 atm)

no reaction(~20% Conv. at rt)

t-Bu[(allyl)NiBr]2 0.14 mol%

NaBARF, L*

-70 °C, DCM(1 atm) PPh2

OBnn

t-Bu t-Bu

With n = 099% Yield

98% Regioselectivity2:1 dr

0.45 mol%Ni(cod)2, Et2AlCl, P*

0 °C, toluene

OPPh2

OPPh2

NPPh2Me

AMPPQuant. 93% ee

? Selectivity

Catalytic hydrovinylation of 1,3-dienes

Zhang, A.; RajanBabu, T. V. J. Am. Chem. Soc. 2006, 128, 54.RajanBabu, T. V. Synlett 2009, 853.

[(allyl)NiBr]2 0.14 mol%NaBARF, L*

-70 °C, DCM(1 atm)

PPh2

OBn

BnO

OBn

OPh MeO2C

94% Conversion>99% Regioselect.

>99% Conversion68% Regioselect.


>99% Conversion>99% Regioselect.


97% Conversion>99% Regioselect.



Asymmetric calatysis : comparison with the previous MeDuPhos chiral hemilabile system

O

Ph

Substrate

P

O

O

O

OP N

Ph

Ph

Conv.(%) Select. (%) ee (%) Conv.(%) Select. (%) ee (%)

>99

>99

>99

88

>99

97

>99

>99

85

93

38

<5

>99

>99

>99

0

>99

>99

>99

0

96

99

95

0

Zhang, A.; RajanBabu, T. V. J. Am. Chem. Soc. 2006, 128, 54.RajanBabu, T. V. Synlett 2009, 853.

Is the Feringa’s ligand the way to catalyze hydrovinylation with every substrate?

Bu Many products

Ph

(1 atm)

[(allyl)NiBr]2 1 mol%

NaBARF, DCM, -70 °CPh

Me

99%, 80% ee

O

OP N

Ph

Ph

(1 atm)

[(allyl)NiBr]2 1 mol%

NaBARF, DCM, -70 °C

O

OP N

Ph

Ph

Smith, C. R.; RajanBabu, T. V. Org. Lett. 2008, 10, 1657.Smith, C. R.; RajanBabu, T. V. J. Org. Chem. 2009, 74, 3066.

Colbalt-catalyzed hydrovinylation of unactivated dienes

Sharma, R. K.; RajanBabu, T. V. J. Am. Chem. Soc. 2010, 132, 3295.Grutters, M. M. P.; Müller, C.; Vogt, D. J. Am. Chem. Soc. 2006, 128, 7414.

R

CoCl2 (5 mol%)dppb (5 mol%),

Me3Al (15 mol%)

DCM:toluene (4:1), Temp (°C)(1 atm)

R R

RR

PPh2Ph2P

A B

C D

R Temp. (°C) P PA (%) B (%) C (%) D (%)

n-Pentyl

n-Pentyl

n-Pentyl

n-Pentyl

n-Pentyl

n-Hexyl

n-Heptyl

n-Octyl

n-Methyl

BnO(CH2)2

-10

-20

-10

-20

-10

-10

-10

-10

-10

0

dppb

dppm

dppe

dppp

2 PPh3

dppb

dppb

dppb

dppb

dppb

93

<2

70

75

0

93

95

95

95

78

7

30

0

0

0

7

0

0

1

0

0

67

0

0

0

0

0

0

0

0

0

<2

10

14

0

0

<2

<2

0

0

Catalytic cycle (Part 1)

Sharma, R. K.; RajanBabu, T. V. J. Am. Chem. Soc. 2010, 132, 3295.

CoCl

Cl

R

R

Active catalyst

CoP

HP

Me2AlCl2

P

P

Me3Al Me2AlCl

CoCl

Me

P

P

Me2AlCl Me2AlCl2

Co MeP

P

Me2AlCl2

CoMeP

P

R

Me2AlCl2

CoP

P

Me2AlCl2R

MeMe

Catalytic cycle (Part 2)


Active catalyst

CoP

HP

Me2AlCl2R

CoP

PH

R

CoP

P

R

CoP

P

R

CoP

P

R

Me

R

Me

A

Asymmetric version using Kagan’s DIOPV (or BDPP)


O

O

PPh2

PPh2

(R,R)-DIOP

PPh2

PPh2

(S,S)-BDPP

R

CoCl2 (5 mol%)dppb (5 mol%),

Me3Al (15 mol%)

DCM:toluene (4:1) -45 °C, 6 h

(1 atm) R

R P P yield (%) ee (%)

n-Pentyl

n-Pentyl

n-Hexyl

n-Heptyl

n-Octyl

Methyl

BnO(CH2)2

BnO(CH2)2

(R,R)-DIOP

(S,S)-BDPP

(R,R)-DIOP

(R,R)-DIOP

(R,R)-DIOP

(R,R)-DIOP

(R,R)-DIOP

(S,S)-DIOP

95

96

96

98

95

90

40

40

95

97

95

95

96

90

99

96

Ph

Me(S,S)-BDPP 99 <5%

Recent developpements in heterodimerisation reactions : Iron catalyzed reaction (T. Ritter)

Moreau, B.; Wu, J. Y.; Ritter, T. Org. Lett. 2009, 11, 337.

R1

R2

R3+ R1

R2

R3

Me

NN Ph

X

2 mol%Pyridine + FeCl2

Mg (4 mol%), Et2O

Me

Me

Me

t-BuMe

Me

Me

AcO

X = Me or CH2TMS

Me

Me

F

Both alkenes are (E)at >99:1

Me

MeO

Me

MePh

Me

Me

Me

Ph

Me

92% 85%74%

91:9 Regioselectivity

51%96:4 Regioselectivity

77%98:2 Regioselectivity

79%

Recent developpements in heterodimerisation reactions : Iron catalyzed reaction (T. Ritter)

Moreau, B.; Wu, J. Y.; Ritter, T. Org. Lett. 2009, 11, 337.

NFe

Cl

Cl

N

Me

Mg(0) NFe

N

Me

PhHE

Hz NFe

N

Me

Ph

FePh

HzHE

Me

NN

H

PhFe

Hz

HE

Me NN

Ph Me

HE

FeHZ

N N

Me

Ph Me

HE

Hz

Recent developpements in heterodimerisation reactions : branched-branched coupling

Ho, C.-Y.; He, L. Angew. Chem., Int Ed. 2010, 49, ASAP.Ho, C.-Y.; Jamison, T. F. Angew. Chem., Int. Ed. 2007, 46, 782

Ar R

N N

Ni i-Pr

i-Pr

i-Pr

i-Pr

HTfO

Toluene, rt

"generated in situ"

5 mol%

ArR

In situ conditions:

5 mol% Ni(cod)25 mol% IPr

1-octeneTESOTf, Et3N

MeO

O ONi

Arn-hexyl

H

TfOIPrTES

Arn-hexyl

OTES

N N

Ni i-Pr

i-Pr

i-Pr

i-Pr

HTfO



Ar R

N N

Ni i-Pr

i-Pr

i-Pr

i-Pr

HTfO

Toluene, rt

"generated in situ"

5 mol%

ArR

Me Me MeMe

MeOAcO

Me Me Me

Ph

Me

Ph

Et

MeO

91%86% Hetero.

92%89% Hetero.

90%88% Hetero.

68%94% Hetero.

72%69% Hetero.

90%87% Hetero.

81%87% Hetero.

92%95% Hetero.

77%>99% Hetero.

5555



IPr

NiTfO H

IPr

NiTfO

Ar

Ar

R

IPr

NiTfO

HAr

R

IPr

NiTfO

HAr

R

vs

IPr

NiTfO

H

R

Ar

ArR

• New chemistry for the incorportation of an « ethylene » unit on activated and non-activated olefins Highly catalytic reaction amenable to asymmetric

synthesis

• These methodologies are now ready to be applied to the synthesis of more complex natural molecules

• Broadly applicable control elements to improve selectivity of useful organic transformations Tunable hemilabile ligands Counter-ion effects Acyclic stereocontrol in diene chemistry

Conclusions

Don’t let ethylene ripen your fruits!

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