Sébastien R. Goudreau

R1

R3M

R1 R3

MR2 R2Chiral Reagent

R1R3

M R2

*Aux

R3M

*Aux R3

MR2 R2

Aux*R3

M R2

Sébastien R. Goudreau

Literature Meeting

Enantioselective Carbometallation Enantioselective Carbometallation of Unactivated Olefinsof Unactivated Olefins

September 16th, 2008

2

R1

O

R1R3LG

O

R2

R3

R2

M

R1 R1R3LG

R2

R3

R2

M

R1 X

O

R1 R2

R2M O

R1 X R1 R2

R2M

R1 R2 R1R2

R3

R3M

OO

R1 R2

O

R1

HO

R2

R3R3M

R1 R2 R1R2

R3

R3M

R1 R2 R1

Me

R2

R3R3M

Introduction: Formation of C-C BondsIntroduction: Formation of C-C Bonds

Carbonyl Chemistry Olefines Chemistry

3

BH3

R1 R1 H

BH2

HydroborationR2 R2

R1 H

O EtMgBr

R1

O

Et

MgBrCarbometallation

R1

O

Et

MeIMe

R1 H

EtMgBr

R1 Et

MgBrCarbometallation

R1 Et

MeIMeR2 R2 R2

R1 Et

R1

MgBr

R1 H

Anionic Polymerization (Ziegler)

R2

R2

R2

CarbometallationCarbometallation

RegioselectivityDiastereoselectivityEnantioselectivity

Ziegler et al. Chem. Ber. 1928, 61, 253

4

Enantioslective Carbometallation of Unactivated OlefinesEnantioslective Carbometallation of Unactivated Olefines

Pd and Ni will not be included

Zn, Cu, Mg, Al, Li

Marek Perkin Trans. 1 1999, 535

R1

R3M

R1 R3


R1R3

M R2

*Aux

R3M

*Aux R3

MR2 R2

Aux*R3

M R2

5

I. Marek Technion-Israel Institute of

Technology

J. F. NormantUniversité P. et M. Curie

ZincZinc

E. Nakamura The University of Tokyo

N

R1Me

R2

Me

CO2MeN

R1Me

Me

CO2MeNCO2Me

R2

R3

R1Me

R2

R3 R3

i. 1 equiv LDA, Et2O

iii. H3O+ii. 2 equiv ZnBr2

+

Addition of Zinc EnolateAddition of Zinc Enolate

Marek, Normand et al. JOC 1998, 63, 2442

N

PhMe

Et

Me

CO2Me

69% yielddr = 60:40

N

PhMe

Et

Me Me

CO2Me

65% yielddr > 95:5

N

PhMe

Me

CO2Me

93% yielddr = 98:2

N

cHexMe

Me

CO2Me

60% yielddr = 98:2

N

PhMe

Me

CO2Me

dr = 98:2

H2, Pd/C 10%

87% NH

Me

CO2Me NH

Me

CO2Hsapon.

85%

96% ee

Synthesis of Proline DerivativeSynthesis of Proline Derivative


INR

Me i. t-BuLi (2 equiv)ii. Allyl MgBr (2 equiv)iii. ZnBr2 (2 equiv)

-40 °C, Et2Othen H3O+ Me

NR

Me

INR

Me

LiNR

Me

ZnBr

LiNR

Me

ZnBr

LiNR

Mei. Allyl MgBrii. ZnBr2t-BuLi

Marek, Normand et al. TL 1998, 39, 4821

Allylation of AlkeneAllylation of Alkene

INR

Me i. t-BuLi (2 equiv)ii. Allyl MgBr (2 equiv)iii. ZnBr2 (2 equiv)


NR

Me

Me

NMe

Me

Me

NBn

Me

76% yielddr 96:4

72% yielddr 95:5

Me

NMe

Me

60% yield*dr 80:20*

*starting alkene = E



INMe

Me Ph

LiNMe

Me Ph

ZnBr

LiNMe

Me Ph

ZnBr

LiNMe

Mei. Allyl MgBrii. ZnBr2t-BuLi

OHOLi

Ph

INMe

Me Ph

OLiMeLi OLi

OLi

Me

NR

Me

OH

Ph

H2O

INR

Me

i. MeLi (1 equiv)ii. t-BuLi (2 equiv)iii. Allyl MgBr (2 equiv)iv. ZnBr2 (2 equiv)


NR

Me

OH

R2R1

OH

R2R1

10

Marek, Normand et al. Seances Acad. Sci., Ser. II 1998, 621


Me

NMe

Me

OH

Ph

Me

NMe

Me

OH

Ph

70% yielddr 88:12

75% yielddr 74:26

Me

N

Me

OH

Ph

55% yielddr 60:40

Me

N

Me

OH

Ph

60% yielddr 98:2

iPrH

INR

Me

i. MeLi (1 equiv)ii. t-BuLi (2 equiv)iii. Allyl MgBr (2 equiv)iv. ZnBr2 (2 equiv)


NR

Me

OH

R2R1

OH

R2R1

Marek, Normand et al. Seances Acad. Sci., Ser. II 1998, 621


I

i. t-BuLi (2 equiv)ii. Allyl MgBr (2 equiv)iii. ZnBr2 (2 equiv)


NN

Ph Me

Ph

Me

NN

Ph Me

Me

Ph

70% yielddr > 95:5

HCl 1%Me

ODiBAL-H

OH

12



OOZnR1R2

R3

OO

HR3

R2

+THF, rt

OO Zn

OO

Me

Me

OO

Zn

R2R3

Me

Me

Me

Me

ax

eq R2

R3

L

R1

R1 L

Allylation of CyclopropeneAllylation of Cyclopropene

Nakamura et al. JACS 1993, 115, 5867

OOZnR1R2

R3

OO

HR3

R2

+THF, rt

OO

HMe

Me

OO

HH

Ph

98% yielddr 97:3

80% yielddr 91:9

D

qenched with D2OR1 = mesityl

qenched with H2OR1 = t-Bu



Zn

OO

R2

R3

N

N

O

O

iPr

iPr

ZnOO

R2R3

NN

OO

iPriPr


OO

OO

HR3

R2

THF, rt

N N

O O

iPr iPrZn

R3R2

+


ent ent

OOH

89% yield> 98% ee

OOH

90% yield93% ee

MeMe

OOH

86% yield56% eedr 73:27

Ph

OOH

94% yield62% eedr 83:17

cHex

OO

OO

HR3

R2

THF, rt

N N

O O

iPr iPrZn

R3R2

+



OO O

O

R2

R5

R4

THF, 0 °CR2

R3

NNR1Zn

OMeN

NMeO

+

O

ONN

MeO

EtEt

H

92% yielddr 78:22

O

ONN

MeO

H

87% yielddr > 98:2

HH

Addition on Cyclopropene: Enders’ HydrazoneAddition on Cyclopropene: Enders’ Hydrazone

Nakamura et al. JOC 1997, 62, 792

THF, 0 °CN

NR1ZnOMe+ N

NMeO

42% yielddr 82:18

Nakamura et al. Angew 1997, 36, 2491

Addition on Alkene: Enders’ HydrazoneAddition on Alkene: Enders’ Hydrazone

19

CopperCopper

E. Nakamura The University of Tokyo

OO

Me

Me

RCu

RR

H

OO

R1

OO

R1

(R2)2CuX

R2THF, -70 °Cthen MeOH

Addition on CyclopropeneAddition on Cyclopropene


OO

Me

Me

R

CuRO

O

Me

Me

ax

eq

OO

HMe

77% yielddr 72:28

Me2CuLi

OO

HBu

85% yielddr 71:29

Bu2CuLi

90% yielddr 65:35

Bu2CuMgBr

OO

HHex

90% yielddr 60:40

Hex2CuLi

OO

H84% yield

dr 96:4trans-1-hexenyl-Cu(CN)(Th)Li2

OO

MeEt

89% yielddr 96:4

Me2CuLi

92% yielddr 90:10

Me2CuMgBr

OO

MePh

65% yielddr 99:1

Me2CuLi

78% yielddr 92:8

Me2CuMgBr

OO

EtPh

90% yielddr 97:3

Et2CuMgBr

OO

BuPh

81% yielddr 97:3

Bu2CuLi



OO

R1

OO

R1

(R2)2CuX

R2THF, -70 °Cthen MeOH

OO

Et

Me2CuLi

THF, -70 °COO

MeEt

CuMeLi

OO

MeEt

CO2Et

OO

MeEt

Ph

O

OO

MeEt

ClCO2Et

H



23

MagnesiumMagnesium

A. H. Hoveyda, Boston College

24

MeN

OH

Ligand*

R

Me

ROH

OH

E

MeMgCl (8 equiv)

LiCl (3 equiv)THF/toluene, -50 °C

MeOH (1 equiv)Ligand* (3 equiv)

Ph

Me

OHPh

Me

H+ quench73%

93% ee

Ph

Me

OH

I

O

O

Ph

Me

OH

SPh

CO2 quench55%

96% ee

I2 quench64%

98% ee

(PhS)2 quench66%

91% ee

Ph

Me

OH

allyl-Br, cat CuI65%

94% ee

Ph

Me

2-bromoallylbromidecat CuI, 69%

94% ee

Br

Ph

Me

O

OH

DMF quench66%

98% ee

OHTMS

Me

OH

H+ quench81%

91% ee

Si

Me

OH

H+ quench79%

90% ee

Ph

MeMe

Me

OH

H+ quench81%

94% ee

Cl

Addition of Grignard on CyclopropeneAddition of Grignard on Cyclopropene

Fox et al. JACS 2006, 128, 5600

O

Me

HO

H

(EBTHI)ZrCl2(10 mol %)

EtMgCl (5 equiv)

THF, rt

Zr

(EBTHI)ZrCl2

ZrClCl 2 EtMgBr

THF

Zr Zr H

ethylene-1,2-bis(η5-4,5,6,7-tetrahydro-1-indenyl)zirconium dichloride

Mg: Zr CatalysisMg: Zr Catalysis

Hoveyda et al. JACS 1993, 115, 6997

ZrO

ClMg

OClMgO

ClMgO

ClMgO

ZrL* ZrL*EtH

ZrL*H

H

EtMgCl

Zr

O

HH

Zr

O



Zr

H

Me Zr

O

HH

Me

Zr Zr

O

HH

Me Me

OMe

HO

H

HO

H

Me

MeO



O

Me

HO

H

65% yield>97% ee

Me

HO

H

40% yield>95% ee

HO

HMe

2.3:1

Me

N

Me

HN

H

75% yield>95% ee

n-nonyl

n-nonyl

(EBTHI)ZrCl2

ZrClCl

Alkene ProductRMgCl (5 equiv)

THF, rt




O

Me

HO

H

65% yield>97% ee

Me

HO

H

40% yield>95% ee

HO

HMe

2.3:1

Me

N

Me

HN

H

75% yield>95% ee

n-nonyl

n-nonyl


(EBTHI)ZrCl2

ZrClCl


THF, rt



O

MeH

HO

73% yield95% ee

MeH

HO

40% yield98% ee

Me

OO

Me

HO

H

65% yield90% ee

O

MeH

75% yield92% ee

OH


(EBTHI)ZrCl2

ZrClCl


THF, rt



NTs

MeH

NHTs

76% yield>98% ee

NTs

MeH

77% yield>98% ee

NHTs

NTs

MeH

NHTs

72% yield>98% ee


(EBTHI)ZrCl2

ZrClCl


THF, rt



HN

Me

O

O

MeMe

OHO

H2N

Me

OH

Sch 38516(fluvirucin B1)

HN

Me

OH

O

MeMe

OOH

EtEtMgBrZrCp*2 (10 mol %)

O

EtOH

65%, >97% ee

Synthesis of Sch 38516 Aglycon MacrolactamSynthesis of Sch 38516 Aglycon Macrolactam

Hoveyda et al. JACS 1995, 117, 2943Hoveyda et al. JACS 1997, 119, 10302

Me

OH

EtNH2

O

EtOH

Me

OTBS

EtNH

O

EtHN

Me

OTBS

O

MeMe

HN

Me

OH

O

MeMe

+Me

OH1) DCC, HOBT N-methyl morpholine

54%

2) TBSOTf 2,6-lutidine

Grub's I cat(25 mol %)

Benz., 50 °C

60%

1) H2, Pd/C 10% (75%)

2) HF, MeCN (80%)

Synthesis of Sch 38516 Aglycon MacrolactamSynthesis of Sch 38516 Aglycon Macrolactam


OMe OMe

Me

OHOO

O

Me

OTBS OO

Me OTBSMe

60% conv.>99% ee

63% conv.>99% ee

59% conv.>99% ee

60% conv.>41% ee(25 °C)

60% conv.>99% ee

58% conv.>99% ee(20 mol %)

61% conv.>94% ee


EtMgCl (5 equiv)

THF, 70 °COR

racemic enantio-enriched

n

OR n

Kinetic Resolution of PyransKinetic Resolution of Pyrans


(EBTHI)ZrCl2

ZrClCl

OMe O Me

MeO

OOTBS

O Me O Me

58% conv.>99% ee

58% conv.>99% ee

60% conv.70% ee

63% conv.96% ee

60% conv.60% ee

63% conv.79% ee



(EBTHI)ZrCl2

ZrClCl


EtMgCl (5 equiv)

THF, 70 °COR


n

OR n

ZrO

RHZr

O RH

ClMg

ZrL* ZrL*EtH

ZrL*H

H

OOMgCl

OMgCl

OMgCl

Zr

ORH

Zr HH

OR

EtMgCl



Zr

O R

R

Zr

O

R

Zr

O

H

ClMg

O

H

ClMgO

ClMgO

ClMgO

ZrL* ZrL*EtH

ZrL*H

H

RR

R

R

EtMgCl

Kinetic Resolution of FuransKinetic Resolution of Furans

Hoveyda et al. Tetrahedron 1995, 51, 4383

Zr

O

Zr

O

H

ClMg

O

H

ClMgO

ClMgO

ClMgO

ZrL* ZrL*EtH

ZrL*H

H

R

R

EtMgCl

RR

R

R




A Bsubstrate yield (%) ee (%) yield (%) ee (%) anti:syn

OMe

48 98 48 98 95:5

O 49 96 49 >95 95:5

O Me

Me31 98 33 98 95:5

O 23 >95 26 99 99:1

EtMgCl (5 equiv)

THF, 70 °C

racemic

O RR

OHEt

OH

EtR+

A B


(EBTHI)ZrCl2

ZrClCl


OBnOBn OPh

OPh

Me

OO OBnOBn OPh OPh

65% conv.52% ee

60% conv.81% ee

60% conv.97% ee

55% conv.98% ee

60% conv.82% ee

60% conv.70% ee

56% conv.>99% ee

60% conv.81% ee

EtMgCl (5 equiv)

THF, 70 °C

OR

n

OR

n



Kinetic Resolution of Allylic EthersKinetic Resolution of Allylic Ethers


(EBTHI)ZrCl2

ZrClCl

Zr

ROH

ZrRO

HZr

ORH

n n

n

Favored


EtMgCl (5 equiv)

THF, 70 °C

OR

n

OR

n



(EBTHI)ZrCl2

ZrClCl

Kinetic Resolution of Allylic EthersKinetic Resolution of Allylic Ethers

O

OH

F

Me 1) K2CO3acetone (80%)

2) TBSOTf 2,6-lutidine (93%)

+

O

F

Me

TBSO

ZrCp*2 (10 mol %)EtMgCl (5 equiv)

THF, 70 °C

rac rac

O

F

Me

TBSO44%

(R,R)

O

F

OTBSH

Shrock's cat (4 mol%)ethylene (1 atm)

Benzene, 24 h97% O

FNH2

OTBSH

Synthesis of NebivololSynthesis of Nebivolol


O NH OH

OOH

F F

(S,R,R,R)-nebivolol

O NH OH

OOH

F F

(S,R,R,R)-nebivolol

O

OH

F

Me 1) Pd(PPh3)4THF (84%)

2) TBSOTf 2,6-lutidine (93%)

+

O

F

Me

TBSO

ZrCp*2 (10 mol %)EtMgCl (5 equiv)

THF, 70 °C

rac rac

O

F

Me

TBSO40%

(R,R)

O

F

OTBSH

Shrock's cat (4 mol%)ethylene (1 atm)

Benzene, 24 h97% O

FO

OTBSH



O NH OH

OOH

F F

(S,R,R,R)-nebivololO

FO

OTBSH

O

FNH2

OTBSH 1) NaBH(OAc)3 (1.4 equiv)

1,2-dichloroethane, 2h (91%)

2) 10% HCl MeOH, 30 min (97%)



NPh

H

(MeS)2 quench95%

75% ee

Et

SMe

NPh

Me

Et

SMe(MeS)2 quench

61%52% ee

NEt

OH

Ph

O2 quench37%

52% ee

NEt

OH

PhN

O2 quench50%

42% ee

HO

(H2O quench75%

56% ee

Et

H

Zr

ZrCpL*

Addition on AlkeneAddition on Alkene

Whitby et al. TL 1996, 39, 7139

ZrCpL* (4 mol %)Et2Mg (5 equiv)

THF, rtX X

then E+ quench

Et

E

46

AluminiumAluminium

Ei-ichi NegishiPerdue University

47

R OHR

i. Me3AlCl2ZrCp2* (8 mol %)

ii. O2

Cl2ZrCp2*

ZrCl Cl

R ZrCp2*RCl2ZrCp2* (8 mol %)

Me3Al

AlMe2RAlMe3 O2

OHR

Methylation of AlkeneMethylation of Alkene

Negishi et al. JACS 1995, 117, 10771

48

OH OH OHOH

OH

Si OHHO

OH H2N OH

88%72% ee

92%74% ee

80%65% ee

7%70% ee

30%85% ee

81%74% ee

79%75% ee

68%71% ee

R OHR

i. Me3AlCl2ZrCp2* (8 mol %)

ii. O2

Si

Cl2ZrCp2*

ZrCl Cl



49

n-BuOH

Et

Si

Et

OH

H2N OHEt

n-OctOH

Et

i-BuOH

EtOH

EtPh

n-OctOH

n-Pr

n-PrOH

n-Oct

74%93% ee

64%92% ee

77%90% ee

69%93% ee

56%95% ee

66%96% ee

62%91% ee

59%85% ee

R1 OHR1

R2

i. (R2)3AlCl2ZrCp2* (8 mol %)

ii. O2


Si

Cl2ZrCp2*

ZrCl Cl


51

LithiumLithium

I. Marek Technion-Israel Institute of

Technology

J. F. NormantUniversité P. et M. Curie

52

N N

(–)-sparteine

Ph OHn-Bu

Ph Ot-Bun-Bu

Ph NMe2

n-BuPh NHMe

n-BuPh NMeBn

n-Bu

Phn-Bu

OH Ph OHEt

Ph OHs-Bu

Ph OHt-Bu

Ph OHBn

SPh

Ph OHn-Bu

SPh

Ph OHn-Bu

Me

Phn-Bu

OH

82%80% ee

71%80% ee

70%82% ee

62%66% ee

64%84% ee

72%70% ee

68%85% ee

65%72% ee

40%0% ee

67%0% ee

(PhS)2 quench

61%83% ee

(PhS)2 quench

63%82% ee

MeI quench

72%70% ee

Marek, Normand et al. JACS 1995, 117, 8853Marek, Normand et al. TL 1997, 38, 7523

Ph XR

R1Li(–)-sparteine

cumene, 0 °CPh XR

R1

then H2O

Li: Marek & NormandLi: Marek & Normand

53

Ph On-Bu

OMe Ph OHex

OMe Ph Os-Bu

OMe Ph OHept

OMe

1 equiv: 72%, 95% ee 1 equiv: 70%, 94% ee 1 equiv: 80%, 90% ee 1 equiv: 50%, 90% ee

0.1 equiv: 67%, 92% ee 0.1 equiv: 65%, 92% ee 0.1 equiv: 77%, 92% ee0.01 equiv: 50%, 85% ee



N N

(–)-sparteine

R1Li(–)-sparteine

cumene, -50 °Cthen H2O

Ph O Ph OR1

OMe OMe

54

R1Li(–)-sparteine

cumene, -50 °Cthen H2O

Ph O Ph OR1

OMe OMe

Ph

Li O

OMe

R1

Li

OR1

OMePhR1PhHH

H2OPh O

R1OMe

R1Li(–)-sparteine

cumene, -50 °CPh O OMe

H

E+ Ph OR1

OMe

E

20 °C

Marek, Normand et al. JOC 1997, 62, 4898Marek, Normand et al. Synlett 2002, 3, 423

N N

(–)-sparteine


55

Ph

n-Bu

61%92% ee

Ph

s-Bu

66%92% ee

Ph

Hex

59%92% ee

R1Li(–)-sparteine (10 mol %)

hexane, -10 °CPh O OMe

Ph

R1

Marek, Normand et al. JOC 1997, 62, 4898Marek, Normand et al. Synlett 2002, 3, 423

N N

(–)-sparteine


56

n-Bu

70%72% ee

n-Hex

61%50% ee

n-Bu

53%83% ee

Ph

n-Hex

45%73% ee

Ph

n-Bu

60%55% ee

TMS

n-Hex

52%52% ee

TMS

n-Bu

60%54% ee

i-Pr

n-Hex

50%50% ee

i-Pr

R1Li(–)-sparteine (10 mol %)

hexane, -10 °CO OMeR2

R1

R2

Marek, Normand et al. Synlett 2002, 3, 423

N N

(–)-sparteine


57

R1Li(–)-sparteine (1 equiv)

hexane, -15 °Cthen H2O

PhMe Ph

Me

R1

PhMe

n-BuPh

Me

HexPh

Me

Pr

83%85% ee

88%84% ee

92%76% ee

Marek, Normand et al. TL 1997, 38, 7523Marek, Normand et al. TL 2000, 41, 6575

N N

(–)-sparteine


58

n-BuLi(–)-sparteine (2 equiv)

then E+

PhPh

n-BuE

Et2O, -78°C

76%24% ee

Phn-Bu

CO2H

Phn-Bu

SMe

Phn-Bu

CONMe2

Phn-Bu

CS2H

73%24% ee(-65 °C)

66%11% ee

72%0% ee

Taylor et al. Tet. Ass. 1997, 8, 665

N N

(–)-sparteine


59

n-BuLi(–)-sparteine (2 equiv)

then CO2

n-BuCO2H

Et2O, -78°C

R R

72%58% ee

(Cumene, -95 °C)

n-BuCO2HOMe

n-BuCO2HO

OMe

n-BuCO2HO

n-BuCO2HOBn

n-BuCO2HSMe

n-BuCO2H

MeO

n-BuCO2H

Me2N

n-BuCO2H

HO

n-BuCO2HHO2C

n-BuCO2HPh

50%67% ee

(Cumene, -94 °C)

67%50% ee

(Cumene, -94 °C)

70%31% ee

(Hexane, -78 °C)

75%10% ee

(Et2O, -78 °C)

68%7% ee

(Cumene, -94 °C)

80%0% ee

(Hexane, -78 °C)

63%5% ee

(Cumene, -78 °C)

19%15% ee

(Hexane-Cumene, -78 °C)

80%41% ee

(Cumene, -78 °C)

Li: TaylorLi: Taylor

Taylor et al. Tet. Ass. 1997, 8, 665

N N

(–)-sparteine

60

NBn

Br

NBn

E

toluene, -90 °C

t-BuLi(–)-sparteine (1.5 equiv)

then MeOH or Br(CH2)2Br

R R

NBn

Br

NBn

BnO

NBn

BrBnO

NBnBnO

NBn

Br

BnO

NBn

Me

NBn

BrMe

NBn

F

NBn

BrF

70%85% ee

80%87% ee(78 °C)

68%85% ee(-78 °C)

86%88% ee(-78 °C)

78%82% ee(-78 °C)

90%89% ee

80%87% ee

80%90% ee

65%88% ee

NBn

85%87% ee

Li: Groth & BaileyLi: Groth & Bailey

Bailey et al. JACS 2000, 122, 6787Groth et al. JACS 2000, 122, 6789

N N

(–)-sparteine

61

toluene, -80 °C

t-BuLi(–)-sparteine (1.5 equiv)

then MeOHNBn

Br

NBnR

R

34%93% ee

NH

OH

NH

OMe

NH

OTHP

NH

OTIPS

NH

OMe

NH

SPh

NH

SMe

NH

NMe2

NH

NH

Ph

57%60% ee(25 °C)

30%72% ee(25 °C)

69%80% ee(25 °C)

0%(25 °C)

33%30% ee

81%88% ee

75%87% ee

81%91% ee

83%85% ee

Groth et al. Synlett 2008, 1301

N N

(–)-sparteine


62

hexane, -78 °C to rt

t-BuLi(–)-sparteine (3 equiv)

O

Br

TMSX

OX

TMS

t-BuLi

OO

Br

TMS

OLi

TMS

X

X

X

TMSLi

O

Li

TMSX

OH

TMS

X

MeOH

Barluenga et al. OL 2002, 4, 2225

N N

(–)-sparteine


63

hexane, -78 °C to rt

t-BuLi(–)-sparteine (3 equiv)

O

Br

TMS OH

TMS

X X

74%71% ee

OH

Me

TMS

OH

Cl

TMS

OH

F

TMS

OH

MeO

TMS

OH

TMS

F

76%80% ee

79%76% ee

64%78% ee

60%57% ee

Barluenga et al. OL 2002, 4, 2225

N N

(–)-sparteine


64

ConclusionConclusion

Zn, Cu, Mg, Al, Li

R1

R3M

R1 R3


R1R3

M R2

*Aux

R3M

*Aux R3

MR2 R2

Aux*R3

M R2

65

ThanksThanks

Documents

Sébastien R. Goudreau