Construction of Aryliridium Salen Complexesccc.chem.pitt.edu/wipf/Current Literature/Marija_4.pdf · Marija Manojlovic@ Wipf Group Page 6 of 13 7/22/2008. Title Paper – Aryliridium-Salen

Construction of Aryliridium – Salen Complexes:Enantio- and Cis-Selective Cyclopropanation of

Conjugated and Nonconjugated Olefins

Katsuki et al. JACS ASAP.

Marija ManojlovićWipf Group Current Litarature Meeting

7-19-08

Marija Manojlovic@ Wipf Group Page 1 of 13 7/22/2008

Asymmetric CyclopropanationHalometalmethyl mediated Michael Initiated Ring Closure

Transition Metal Catalyzed Other Methods Decomposition of Diazomethane

Ph

Ph

Ph

Ph

O O

TiiPrO O

iPr

OO

Et Et

- Enzyme catalyzed kinetic resolution- Chiral Stoichiometric Carbenes

Chem. Rev. 2003, 103, 977.


Transition Metal Catalyzed Decomposition ofDiazoalkanes

Four main types of diazoalkanes:

Transition metals used:

N2

H (TMS)

H (Ar)

N2

EWG

HN2

EWG1

EWG2N2

EWG

R

- In most cases mechanismis believed to proceedthrough metal carbene.

- Cu, Rh, Ru and Co metalcarbenes react faster withelectron-rich alkenes; Pdcarbenes are optimal forelectron-deficient alkene.

Chem. Rev. 2003, 103, 977.


Transition Metal Catalyzed Asymmetric CarbeneTransfer Cyclopropanation - Overview

R1

R2

R3

Chiralmetal catalyst

N2

EWG

H

R1

R3 R2

EWG

R1

R3 R2

EWG

+

trans cis

R1 = Aryl or vinyl, Metal = Ru, Rh, Co, Cu, Au

The most common carbene sources:

N2

H

N2

CNH

N2

P(OR)2H

N2

SO2RH

N2

NO2H

O

OR

O

Chem. Rev. 2003, 103, 977.



Trans selective catalysts Product scope

PhCO2

tBu

Catalyst 1, 65%t rans : cis 97:3

94% ee

CO2Et

MeO

Catalyst 2, 89%trans : cis 96:4

86% ee

PhCO2BHT


99% ee

1 2

3 4

P(O)OMe2

Ph


85% ee

Cl

O

P(O)OMe2

Ph


86% ee

3

n = 1, R = d-menthyl

5 6

O

O

Catalyst 5, 77%trans : cis > 20:1

80% ee

CO2tBu


96% ee

Cl

CO2tBu


96% ee

CO2tBu

Catalyst 6, 93%trans : cis 47:5399 (93) % ee

Chem. Rev. 2003, 103, 977. ACIE 1992, 31, 430. Org. Lett. 2006, 8, 3437. Bull. Chem. Soc. Jpn. 2001, 74, 2139.



Cis selective catalysts Product scope

Ph CO2Et

Me


90% ee

n-C5H11 CO2Et

Me

Catalyst 1, 64%trans : cis 48:5275 (72) % ee

2

1

3

4

5

Ar = 4-CF3-C6H4

Me

Me

Me

CO2Et


97% ee

Cl

MeO

F

CO2Et


97% ee

Me


91% ee

Ph CO2t-Bu

CO2t -Bu

MeO


95% ee

CO2Et


99% ee

Chem. Rev. 2003, 103, 977. Synlett 1993, 638. Synlett 1999, 1793. Tetrahedron Lett. 2000, 41, 3647. Organometallics 2001, 20, 2120.


Title Paper – Aryliridium-Salen Complexes

Katsuki et al. JACS, ASAP.


Title Paper – Cyclopropanation of ConjugatedAlkenes

Ar2 (1 mol %)

N2CHCO2t-Bu (1.0 eq)THF, -78 °C

Ar

CO2t-Bu

H

R1R1

R2

R3

R2R3

R1

CO2t-Bu

H

ArR3

R2

+

cis-isomer trans-isomer(1-10 eq)

( 2-MeO)C6H4

CO2t- Bu

H

H

90%c is : t r ans 97:3

99% ee

(2-Cl) C6H4

CO2t-Bu

H

H

90%cis : tr ans 99:1

98% ee

(4- Br) C6H4

CO2t-Bu

H

H


93% ee

(4-CF3)C6H4

CO2t-Bu

H

H


97% ee

(4-Me)C6H4

CO2t-Bu

H

H

>99%cis : tr ans 95:5

95% ee

CO2t-Bu

H

Me

51%

c is : t r ans 91:9

98% ee

CO2t- Bu

H

H

trace

MeH

80%

c is : tr ans > 99:1

97% ee

H

H

CO2t -Bu

76%


99% ee

O

H

H

CO2t -Bu

42%


99% ee

O

Me

H

CO 2t -Bu



Title Paper – Cyclopropanation of Dienes andEneynes

CO2Et

H

H

84%

cis : t rans 93:7

95% ee

CO2t-Bu

H

H

90%

cis : t rans 95:5

93% ee

CO2Et

H

H

99%

cis : trans 79:21

94% ee

CO2t-Bu

H

H

> 99%

cis : trans 75:25

97% ee

Ph Ph

Ph Ph

Ph

9:1 E/Z m ixture

2 (1 mol %)

N2CHCO2Et (1.0 eq)THF, -78 °C

Ph

CO2E t

H

H

74% yieldTerm inal : In ternal > 99:1

c is : t rans = 90 :10

Pd/C, H2

MeOH, rt, 9hPh

CO2E t

H

H

> 99% yie ld , 96% ee

R

2 (1 mol %)

N2CHCO2t-Bu (1.0 eq)THF, -78 °C

R

CO2t-Bu

H

H

H

CO2t-Bu

H

R

+

cis-isomer trans-isomer

(5-10 eq)

2 (1 mol %)

N2CHCO2Et (1.0 eq)THF, -78 °C CO2Et

H

H

90% yieldTerminal : Internal > 99:1

cis : trans = 91 :996% ee

5 5



Title Paper – Cyclopropanation of Nonactivated Alkenes

2 (1 mol %)

N2CHCO2Et (1.0 eq)THF, -78 °C CO2Et

H

R1R1

CO2Et

H

R1

+

cis-isomer trans-isomer

AlkylAlkyl Alkyl

(10 eq)

CO2t- Bu

H

H

90%

c is : t r ans 95:5

98% ee

Ph

CO2t-Bu

H

H

95%

cis : tr ans 95:5

97% ee

CO2E t

H

H

62%

c is : t r ans 98:2

98% ee

BnO BzO

CO2Et

H

H

87%

c is : t r ans 96:4

94% ee

CO2E t

H

H

trace

PhO

O CO2E t

H

H

46%

cis : tr ans 96:4

98% ee

CO2E t

H

Me

87%

cis : tr ans 70:30

83% ee

Ph

CO2Et

H

Me

65%

c is : tr ans 56:44

99% ee



Synthesis of 8-[(1R,2S)-2-hexylcyclopropyl]octanoate

- Cyclopropyl fatty acid ester, isolated from Ecsherichia coli

2 (1 mol %)

N2CHCO2Et (1.0 eq)THF, -78 °C CO2E t

H

H

cis : tr ans 98:268%, 98% ee

LAH, THF

0 °C to rt, 2h99 %

H

H

OH

1-pheny l-1H -te trazo le-5-thio lDEAD, PPh3, THF, 0 °C

then H2O, E tO H, (NH4)6Mo7O24 4H2O90%

H HS

O

O N N

NN

Ph

LiHMDS , THF, -78 °C

then MeO2C(CH2)5CHO-78 °C to r t, 73%

H H

OMe

O KO2CCN=NCCO 2K , A cOH

MeOH, reflux, 8h, 88%

H H

OMe

O



Title Paper – Mechanistic Considerations

-Crystal structure of the catalyst 4



Conclusions

• First stable Ir(III) salen complexes that carry apical arylligand were synthesized

• Two of these complexes are shown to be unique andpotent catalysts for cis-selective asymmetriccyclopropanation

• More than 30 different cis-cyclopropyl esters were madein excellent yields and selectivities strating from bothconjugated and unactivated alkenes

• This cyclopropanation was applied to the synthesis ofnatural cyclopropyl fatty acid ester


Documents

Construction of Aryliridium Salen Complexesccc.chem.pitt.edu/wipf/Current Literature/Marija_4.pdf · Marija Manojlovic@ Wipf Group Page 6 of 13 7/22/2008. Title Paper – Aryliridium-Salen