IMPROVED RUTHENIUM CATALYSTS FOR Z-SELECTIVE OLEFIN METATHESIS

IMPROVED RUTHENIUM CATALYSTS IMPROVED RUTHENIUM CATALYSTS FOR FOR

Z-SELECTIVE OLEFIN METATHESISZ-SELECTIVE OLEFIN METATHESISBenjamin K. Keitz, Koji Endo, Paresma R. Patel, Myles B.

Herbert, and Robert H. Grubbs J. Am. Chem. Soc. 2012, 134, 693–699.

Shawn K. CollinsShawn K. CollinsUniversitUniversitéé de Montr de Montrééalal

Department of ChemistryDepartment of ChemistryCentre for Green Chemistry and CatalysisCentre for Green Chemistry and Catalysis

[email protected]@umontreal.caWeb: http://www.mapageweb.umontreal.ca/collinss/Web: http://www.mapageweb.umontreal.ca/collinss/

CHARETTE/COLLINS LITERATURE MEETINGCHARETTE/COLLINS LITERATURE MEETINGUniversité de Montréal (UdeM)Université de Montréal (UdeM)

October 11October 11thth, 2012, 2012Montréal, QuébecMontréal, Québec

CROSS METATHESIS: GENERALIZED MECH USING GRUBBS II

For a review on catalytic cross-metathesis, see: (a) Blechert, S.; Connon, S. J. Angew. Chem., Int. Ed. 2003, 42, 1900;

(b) Vernall, A. J.; Abell, A. D. Aldrichimica Acta 2003, 36, 93; (c) For industrial applications of cross metathesis, see: Pederson, R. L.; Fellows, I. M.; Ung, T. A.; Ishihara H.; Hajela, S. P. Adv. Synth. Catal. 2002, 344, 728.

First proposed by Chauvin: Herrison, J. L.; Chauvin, Y. Makromol. Chem. 1970, 141, 161. and later expanded upon by Katz: Katz, T. J.; McGinnis, J. L. J. Am. Chem. Soc. 1975, 97, 1592.

MesN NMes

RuR

Cl H

MesN NMes

RuR

MesN NMes

RuCl

MesN NMes

Ru

R1

R2

R1Cl

Cl

ClCl

R1

ClR1

R2Cl

MesN NMes

RuR

Cl

Cl

H MesN NMes

RuR

Cl

Cl

H

R1side-binding model bottom-binding

model

or

or

MesN NMes

RuCl

ClR1

side-binding model

bottom-binding model

MesN NMes

RuR

Cl

Cl

H

PCy3

R1

R2

initiation step

propagation step

R2

R1

R2

R1 Z:EYield of cis-product

(%)

(CH2)5CH3 9:1 56

(CH2)7CH3 8.5:1 72

(CH2)3Br 7.3:1 45

(CH2)2Br 9:1 17.5

(CH2)4OTBS 6.7:1 90

(CH2)3OTBS 5.6:1 68

(CH2)2OTBS 5.3:1 73

CH2TMS 3:1 76

o-MeOC6H4CH2 9:1 72

(CH2)6CH=CH2 8:1 53

(CH2)2C(O)OBn 5.6:1 44

(CH2)3CH(OMe)2 7: 1 79

CH2CMe2CH2CH(OMe)2 3: 1 64

Crowe, W. E.; Goldberg, D. R. J. Am. Chem. Soc. 1995, 117, 5162.

Z-SELECTIVE METATHESIS (PREVIOUS): SUBSTRATE CONTROL

+

(1 equiv.)

CN

MoN

Ph

O

O

F3CCF3

F3C

F3C

(5 mol %)rt, CH2Cl2, 3 h

R1

(1 equiv.)

CN

R1

Schrock


Product Z:E Yield

(%)

Product Z:E Yield

(%)

4:1 88 3:1 76

3:1 81 3:1 79

4:1 91 9:1 83

Randl, S.; Gessler, S.; Wakamatsu, H.; Blechert, S. Synlett 2001, 430.

(5 mol %)CH2Cl2

reflux, 2 h+

(2 equiv.)

Substrate Product

Ru

O

NMesMesN

Cl

Cl

CN

GH2

OH

CN

CHO

CN

CO2H

CN

OCOPh

CN

OO

CO2Me

CNCO2Et

CO2Et

CN

Product E:Z Yield

(%)

Product E:Z Yield

(%)

43:57 79 96:4 80

42:58 78 >98:

2

94

1:99 59 >99:

1

86

83:17 74 93:7 60

Kim, M.; Lee, D. Org. Lett. 2005, 7, 1865.


(5 mol %)

CH2Cl2reflux, 4-6 h

+(2-2.5 equiv.)alkynyl boronate

Ru

PCy3

NMesMesN

Cl

Cl

Ph

alkene

1,3-diene product

R2

BPin

R1R2

R1 BPin

BPin

OBn

OTBDMS

BnO

OTBDMS

OAc

BPin

BPin O

OTBDMS

BPin

BPin

TBDMSO

TMS

BPin

MeO

Br

BPin

Br

BPin

MeO

Jiang, A. J.; Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 16630.

Z-SELECTIVE METATHESIS (PREVIOUS): CATALYST CONTROL

C6D6, 22oC

catalyst(4 mol %)

R1 R1 R1

MoN

Ph

N

OBr

TBSO

Br

WN

Ph

N

Cl

Cl

O

MesTBSO

Mes

WNN

O

i-Pr

i-Pr

i-Pr

i-Pri-Pr

i-Pri-Pr

i-Pr

TMSTMS

3h, 33% conv, 98% Z

PhPh

3h, 62% conv, 93% Z

PhPh

14h, 52% conv, 94% Z


MoN

Ph

N

OBr

TBSO

Br

On-Bu or OPMB

+

R

(1.2 - 5.0 mol%)

C6H6, 22C, 2 hOn-Bu OPMB+

R R

On-Bu

OPMB

C8H17

Bn

76% conv., 68% yield98% Z

71% conv., 57% yield>98% Z

On-Bu

OPMB


74% conv., 70% yield>98% Z

Br( )6

PhO2C

On-Bu

OPMB


66% conv., 59% yield>98% Z

TMSCC( )6

TIPSO

On-Bu

OPMB

Cy

57% conv., 51% yield>98% Z

81% conv., 75% yield>98% Z

PhHN

Meek, S. J.; O'Brien, R. V.; Llaveria, J.; Schrock, R. R.; Hoveyda, A. H. Nature 2011, 471, 461-466.


WNN

O

Cl

Cl

i-Pr

i-Pri-Pr

i-Pri-Pr

i-Pr

(7.5 mol%)C6H6 (1M), 0.02 torr, 22C, 4h

82%, 94% Z

(5 mol%), C6H6 (1 mM), 16 h, 22C

96%, 34% Z

O OO

Me

TBSO

Me

MeMe

Me

N

SMe

TBSO OO

Me

TBSO

Me

MeMe

Me

N

SMe

TBS

Ru

O

NMesMesN

Cl

Cl

WNN

O

Cl

Cl

i-Pr

i-Pri-Pr

i-Pri-Pr

i-Pr

NO

N

H

NO

N

H

(5 mol%)PhMe (1M), 1.0 torr, 22C, 8h

63%, 94% Z

(20 mol%), slow additionCSA (300 mol%)

CH2Cl2 (0.2mM), 3.5 h, 40C62%, 63% Z

Ru

PCy3

NMesMesN

Cl

Cl

Ph

Yu, M.; Wang, C.; Kyle, A. F.; Jakubec, P.; Dixon, D. J.; Schrock, R. R.; Hoveyda, A. H. Nature 2011, 479, 88-93.

Z-SELECTIVE METATHESIS (PREVIOUS): CATALYST SYNTHESIS

Ru

O

NMesN

OO

t-Bu

NMesN

Cl

1. KOCMe2Et, hexanes, rt, 1h

2. hexanes, 60C, 4 h

Ru

PCy3

OCl

Cl92 %

Ru

O

NMesN

Cl

Cl

tBuCOOAg (3 eq.)

THF, 10 min59 %

Ru

O

NMesN

OO

t-Bu

Ru

O

NMesMesN

Cl

Cl

tBuCOOAg (2 eq.)

THF, 2 h41 %

Me

Me

Modification of adamantyl group or mesityl group either destroyed reactivity or

prevented metalation of the adamantyl group…

…current manuscript focuses on modification of the anionic group!


Ru

O

NMesN

OO

t-Bu

Me

Me

Ru

O

NMesN

OO

t-Bu

Ru

O

NMesMesN

Cl

ClEtO2C CO2EtEtO2C CO2Et


Ru

O

NMesN

OO

t-Bu

R R R

catalyst(0.1 mol%)

THF [3M], 35C

Ph

3h, 86% Z, 73%

MeO2C

12h, 90% Z, 13%

( )8 Me

12h, 94% Z, 30%

( )5 HO

12h, 43% Z, 81%

( )3

AcO

4h, 89% Z, 62%

PhHN

2h, 71% Z, 67%

Bpin

4h, 94% Z, 74%

TMS

3h, 95% Z, 54%2 mol% 2 mol% 2 mol% 2 mol%

Z-SELECTIVE METATHESIS (PREVIOUS): OLEFIN BINDING


Bulky ligands caused faster

initiation …strange for Hov-type cats

Ru

O

NMesN

OO

t-Bu

NaITHF65%

Ru

O

NMesN

I

AgNO374%

Ru

O

NMesN

OO

NO

NH4NO382%

Monodentate ligands were essentially non-metathesis active…

Faster initiation did not guarantee better catalysts…

Some changes to aryl group (that did give catalysts) did not affect rate (ie Cl

sub for Me)…


Ru

O

NMesN

OO

t-Bu

R R R

catalyst(0.1 mol%)

THF [3M], 35C

Ph

3h, 86% Z, 73%

MeO2C

12h, 90% Z, 13%

( )8 Me

12h, 94% Z, 30%

( )5 HO

12h, 43% Z, 81%

( )3

AcO

4h, 89% Z, 62%

PhHN

2h, 71% Z, 67%

Bpin

4h, 94% Z, 74%

TMS

3h, 95% Z, 54%2 mol% 2 mol% 2 mol% 2 mol%

Ru

O

NMesN

OO

NO

3h, 92% Z, 91% 12h, 91% Z, 85% 12h, 92% Z, 83% 12h, 81% Z, 67%

12h, 95% Z, 8% 12h, 91% Z, 12% 3h, 95% Z, 36% 9h, 95% Z, 14%

NO2 cat. has little secondary metathesis events

SUMMARY.

1) New C−H activated ruthenium catalysts for Z-selective olefin metathesis. Adjusting the ligand environment around the metal center has yielded significant insight into the initiation behavior, activity, and selectivity.

2) Catalysts are capable of ca. 1000 turnovers in several cross-metathesis reactions with very low loadings and do not require reduced pressures, high temperatures, or rigorous exclusion of protic solvents in order to operate effectively.

3) Secondary metathesis events are also relatively slow for the majority of substrates, meaning that significant reaction optimization should not be required.

IMPROVED RUTHENIUM CATALYSTS FOR Z-SELECTIVE OLEFIN METATHESIS

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