反応例 10.2 Grignard 反応と関連反応

アルデヒド，ケトンとの反応

ClMg

Et2O

MgClH2C O1)

2) H2SO4/H2O

OH

64~69%

H. Gilman, W.E. Catlin, Org. Synth., Coll. Vol. 1, 188 (1941).

(CH3)2CHBrMg

Et2O(CH3)2CHMgBr

CH3CHO1)

2) H2SO4/H2O

OH

53~54%

N.L. Drake, G.B. Cooke, Org. Synth., Coll. Vol. 2, 408 (1943).

BrClMg

Et2O

MgBrCl CH3CHO1)

2) H2SO4/H2O

ClOH

82.5~88%

C.G. Overberger, J.H. Saunders, R.E. Allen, R. Gander, Org. Synth., Coll. Vol. 3, 200 (1955).

PhCH2MgCl +

Ph Ph

O1) Et2O !

2) H2O

PhOH

Ph Ph

H2SO4/H2O

!

Ph

PhH

Ph

H. Adkins, W. Zartman,

Org. Synth., Coll. Vol. 2, 606 (1943).

54~59%

O

1) PhMgBr/Et2O !

Ac2O

!

Ph

S

Ph

Ph OH

2) HCl/H2O

42~48% 91~94%

250~270 ˚C

30 min

R. Weiss

Org. Synth., Coll. Vol. 3, 729 (1955).

（脱水）

（脱水素）

有機リチウム化合物

SnPh3PhLi/Et2O Li

O

!

OH1)

2) H2O 70~75%

D. Seyferth, M.A. Weiner, Org. Synth., Coll. Vol. 5, 452 (1973).

N CH3

PhLi/ Et2O

NLi

N

OH1) CH3CHO

2) HCl/H2O

44~50%

L.A. Walter, Org. Synth., Coll. Vol. 5, 452 (1973).

NMe2

CH3

BuLiMe2NCH2CH2NMe2

NMe2

CH3

Li

NMe2

CH3

Ph

OH

Ph

hexane, 25 ˚C

1) Ph2C=O

Et2O, 25 ˚C

2) AcOH49~57%

J.V. Hay, T.M. Harris, Org. Synth., Coll. Vol. 6, 478 (1988).

α,β-不飽和カルボニル化合物への 1,2-付加

CH3CH CHCH

O1) CH3MgCl/Et2O !

CH3CH CHCHCH3

OH

2) NH4Cl/H2O 81~86%

E.R. Coburn, Org. Synth., Coll. Vol. 3, 696 (1955).

Br Mg MgBr Et2O

O

!

Et2O

OH1)

2) H2SO4/H2O

J.C.H. Hwa, H. Sims, Org. Synth., Coll. Vol. 5, 608(1973).

57~59%

HC CH

H

H

O

THF

HC C–MgBr

HC C–MgBr

THF

H OH

+ EtMgBr

+

2) NH4Cl/H2O

1)

58~69%

L. Skattebøl, E.R.H. Jones, M.C. Whiting, Org. Synth., Coll. Vol. 4, 792(1963).

エステルとの反応

2 CH3CH2CH2CH2MgBr H OEt

O

(CH3CH2CH2CH2)2CHOH+1) Et2O

2) H2SO4/H2O 83~85%

G.H.Coleman, D. Craig, Org. Synth., Coll. Vol. 2, 179 (1943).

MgBr

CH3 OEt

O

! Ph

Ph

Ph Ph

CH3 OH

+1) Et2O

2) NH4Cl/H2O

20% H2SO4 C.F.H. Allen, S. Converse,

Org. Synth., Coll. Vol. 1, 226 (1941).

67~70%

2

MgBr

CH3 OEt

O

Ph3C–OH+

1) Et2O

benzene, !

2) H2SO4/H2O 89~93%

W.E. Bachmann, H.P. Hetzner, Org. Synth., Coll. Vol. 3, 869 (1955).

2

3 C2H5MgBrEtO OEt

O

(C2H5)3C–OH+1) Et2O

2) NH4Cl/H2O82~88%

W.W. Moyer, C.S. Marvel, Org. Synth., Coll. Vol. 2, 602 (1943).

（脱水）

OOCH3(CH2)4

CH3(CH2)4

OH

OH

CH3 CH31) CH3MgBr/Et2O, !

2) HCl/H2O, benzene

57%

J. Colonge, R. Marey, Org. Synth., Coll. Vol. 4, 601 (1963).

有機アルカリ金属化合物

CH2

CO2Me

CH3

THF

CH2

C

CH3

OH

BuBu

BuBr + 2Li BuLi + LiBr–20 ˚C

2 BuLi +1) THF, –20 ˚C

2) HCl / H2O

80~86%

P.J. Pearce, D.H. Richards, N.F. Scilly, Org. Synth., Coll. Vol. 6, 478 (1988).

CH3CH C

Br

CH3

LiCH3CH C

Li

CH3

CH3 OEt

O

Et2O Et2O

TsOH

Et2O

OH

73~75%

S. Threlkel, J.E. Bercaw, P.F. Seidler, J.M. Stryker,

R.G. Bergman, Org. Synth., Coll. Vol. 8, 505 (1993).

Cl

EtO OEt

O

COH3 +reflux, 2 h

EtOH, H2O

1)

2)

Na, benzene

3

A.A. Morton, J.R. Myles, W.S. Emerson, Org. Synth., Coll. Vol. 3, 831 (1955).

35~40%

二酸化炭素との反応

R–XMg

R–MgXEt2O

Cl

Cl

(CH3)3C–Cl

Br

R–CO2H

Cl

Br

1) CO2

2) H2SO4/H2O

R–X = !"#72~73%

!"#76~78%

!"#85%

!"#80~85%

H. Gilman, R.H. Kirby, Org. Synth., Coll. Vol. 1, 361 (1941).

R–X = !"#69~70%

S.V. Puntambeker, E.A. Zoellner, Org. Synth., Coll. Vol. 1, 524 (1941).

R–X = !"#68~70%

H. Gilman, N.B.St. John, F. Schlze, Org. Synth., Coll. Vol. 2, 425 (1943).

有機アルカリ金属化合物

N CH3

PhLi

N CH2LiEt2O N CH2CO2Et

1) CO2

2) HCl/EtOH

3) K2CO3/H2O

R.B. Woodward, E.C. Komfeld, Org. Synth., Coll. Vol. 3, 413 (1955).

35~40%

CH3 C C H CH3 C C Na CH3 C C CO2HNa, NH3 1) CO2, THF, Et2O

2) HCl/H2O 50~59%

J.C. Kauer, M. Brown, Org. Synth., Coll. Vol. 5, 1043 (1973).

アミドとの反応

PhCH2CH2ClMg

PhCH2CH2MgCl

NH

O

THFPhCH2CH2CHO

1)

2) HCl/H2O 66~76%

G.A. Olah, M. Arvanaghi, Org. Synth., Coll. Vol. 7, 451 (1990).

ニトリルとの反応

MeOCH2C NEt2O

PhOMe

NMgBr

! PhOMe

O

PhMgBr +H2SO4/H2O

71~78%

R.B. Moffett, R.L. Shriner, Org. Synth., Coll. Vol. 3, 567 (1955).

C

N

CH3MgI

NMgI

CH3

!

O

CH3

Et2O, !

HCl/H2O

52~59%

J.E. Callen, C.A. Donfeld, G.H. Coleman, Org. Synth., Coll. Vol. 3, 26 (1955).

PhCNEt2O

NMgBr

Ph

Ph MeOH

!NH

Ph

Ph

PhMgBr +

P.L. Pickard, T.L. Tolbert, Org. Synth., Coll. Vol. 5, 520 (1973).

61~81%

イミンとの反応

O CH3NH2

H2O

NHCH3

NCH3

Et2O

PhCH2MgCl

NCH3 MgCl

benzene

87~97%

91~96%

R.B. Moffett,

Org. Synth., Coll. Vol. 4, 605 (1963).

エポキシドとの反応

CH3(CH2)3MgBrO Et2O

CH3(CH2)5OH+H2SO4/H2O

1)

2)60~62%

E.E. Dreger, Org. Synth., Coll. Vol. 1, 306 (1941).

BrMg

MgBr

O

Et2O

OH

78~90%

1)

2) NH4Cl/H2O

L.S. Hegedus, M.S. Holden, J.M. McKearin, Org. Synth., Coll. Vol. 7, 501 (1990).

PhMgBr O

OH

Ph

+ 1) CuCl/THF, –30 ̊ C

2) (NH4)2SO4/H2O

80%

A. Schwartz, P. Madan, J.K. Whitesell, R.M. Lawrence, Org. Synth., Coll. Vol. 8, 516 (1993).

オルトエステルとの反応：アセタールとアルデヒドの合成

CH3(CH2)4MgBr + HC(OEt)3

CH3(CH2)4CHO

!

Et2OCH3(CH2)4CH(OEt)2

!"#$%

H2SO4/H2O

45~50%

G.B. Bachman, Org. Synth., Coll. Vol. 2, 323 (1943).

Br

!

!

CHO

MgBr

!

HC(OEt)3

CH(OEt)2

Mg/Et2O

H2SO4/H2O

40~42%

C.A. Dornfeld, G.H. Coleman,

Org. Synth., Coll. Vol. 3, 701 (1955).

Reformatsky 反応

H

O

Ph PhCO2Et

OH

+ BrCH2CO2Et1) Zn, Et2O, benzene, !

2) H2SO4/H2O

61~64%

C.R. Hauser, D.S. Breslow, Org. Synth., Coll. Vol. 3, 408 (1955).

H

O

CH3CHCO2Et

BrOH

CO2Et+1) Zn, benzene, !

2) H2SO4/H2O

K.L. Rinehart, E.G. Perkins, Org. Synth., Coll. Vol. 4, 444 (1963).

CH3CHCO2-s-Bu

Br

CH3(CH2)4 O-s-Bu

OO

CH3

CH3(CH2)4CN +1) Zn, benzene, !

2) H2SO4/H2O50~58%

K.L. Rinehart, Org. Synth., Coll. Vol. 4, 120 (1963).