反応例 17.2 エノラートイオンとエノラート等価体による

炭素－炭素結合形成反応

（Michael反応については反応例 18.1を見ること）

アルドール反応 総説： A.T. Nielsen, W.J. Houlihan, Organic Reactions, 16, 1 (1968).

T. Mukaiyama, Organic Reactions, 28, 203 (1982).

H

O

H3C CH3

O

then HCl

O

!"#$%$&'()

aq. NaOH+

Organic Syntheses, Coll. Vol. 1, p.77 (1941).

H

O

H3C CH3

O

NaOH, EtOH20 - 25 °C

O

!"#$%

2 +

Organic Syntheses, Coll. Vol. 2, p.167 (1943).

H

O

H3C

O O

!"#$%

aq. NaOH

EtOH, 0 °C

+

Organic Syntheses, Coll. Vol. 1, p.78 (1941).

H3C CH3

O

!"#$%$""&'aq. NaOH, 10 °C

then HClO O

OO

H +

Organic Syntheses, Coll. Vol. 1, p.283 (1941); Vol. 7, p.42 (1927).

H3C CH3

O

NaOEt, EtOH–5 °C

!"#$%$"&'(

H

O O

+

Organic Syntheses, Coll. Vol. 3, p.747 (1955); Vol. 23, p.78 (1943).

!"#$%

2

H3C CH3

OBa(OH)2

! CH3

O

HO

CH3H3C

Organic Syntheses, Coll. Vol. 1, p.199 (1941); Vol. 1, p.45 (1921).

O

CHO THF, Et2O, reflux

5% aq. KOH

O

!"#$%

Organic Syntheses, Coll. Vol. 8, p.208 (1993); Vol. 67, p.121 (1989).

EtOH, !

!"#$%$"&'(

+ Ph

O

PhKOH

PhPh

Ph Ph

O

PhPh

O O

Organic Syntheses, Coll. Vol. 3, p.806 (1955); Vol. 23, p.92 (1943).

Ac2O, !

!"#$%$#&'(

Ph H

O

Ph

O

+

CO2H

NaOAc O

O

Ph

PhHC

R. Filler, E.J. Piasek, H.A. leipold, Org. Synth., Coll. Vol. 5, 80 (1973).

リチウムエノラート

O

O 1 . LDA , THF , - 78 °C

2 . i-Pr-CHOO

OOH

!"#$%

Organic Syntheses, Coll. Vol. 7, p.190 (1990).

OSiMe3

O 1 . LDA, THF, - 78 °C

2 . i-Pr-CHOOSiMe3

O

!"#$%

Organic Syntheses, Coll. Vol. 7, p.185 (1990).

エノールシリルエーテル（向山法）

OSiMe3

CH3 CH3

OTiCl4, CH2Cl2

Ph Ph

O OH

+

0 ˚C, 15 min

70~74%

T. Mukaiyama, K. Narasaka, Org. Synth., Coll. Vol. 8, 323 (1993).

イミン（アザエノラート）

!"#$%$"&'(+Na2SO4

-H2OC6H11N CHCH3

(i-C3H7)2NLi, (C2H5)2O

-(i-C3H7)2NHC6H11N CHCH2LiC6H11N CHCH3

(C6H5)2CO

(C2H5)2O, 25 °C

N OLiC6H11

H

H2O

N OHC6H11

H

!)&$%$&*'( !")$%$)+'(

NH2

H CH3

O

O

H

H2O

G. Wittig, A. Hesse, Org. Synth., Coll. Vol. 6, 901 (1988).

Mannich 反応

HCl, EtOH, !

!"#$%$&'()Ph CH3

O

N(CH3)2

CH2=O(CH3)2NH2Cl

Ph

O

Organic Syntheses, Coll. Vol. 3, p.305 (1955).

HCl, EtOH, !

!"#$%$&'()

H3C CH3

O

N+ HEt2Cl–

Et2NH+ Cl–,CH2O, MeOH

H3C

ONaOH, H2O

NEt2H3C

O

Organic Syntheses, Coll. Vol. 4, p.281 (1963).

H2O, 25 °C

!"#$%$&'()

+Me2NH CH2=O Me2NCH2NMe2

CF3CO2H

–15 °C

Me2N=CH2 CF3CO2–

+

CF3CO2HMe2N=CH2 CF3CO2

–+

+ H3C

CH3

CH3

O

–10 to 145 °C

H3C

CH3

O

NMe2

Organic Syntheses, Coll. Vol. 6, p.474 (1988).

Claisen 縮合

総説： C.R. Hauser, B.E. Hudson, Jr., Organic Reactions, 1, 266 (1942).

(Dieckmann反応)：Schaefer, Bloomfield, Organic Reactions, 15, 1 (1967).

CH3COC2H5

ONa

CH3C CHCO2C2H5

ONaAcOH

CH3CCH2CO2C2H5

O

2

28~29%

J.K.H. Inglis, K.C. Roberts, Org. Synth., Coll. Vol. 1, 235 (1941).

CH3OEt

O

EtO C

O

C

O

OEt EtO2C OEt

O

CH3

O

+ 1) Na, EtOH, Et2O

2) AcOH. H2O

60~70%

R.F.B. Cox, S.M. McElvain, Org. Synth., Coll. Vol. 2, 272 (1943).

OEt

O

Ph EtO2C-CO2Et

–CO

O

OEtPh

O OEt

O

OEtPh

O CO2Et

+

1) Na, EtOH 60°C

2) H2SO4, H2O

(85%)

175 ˚C

P.A. Levene, G. M. Meyer. Org. Synth., Coll. Vol. 2, 288 (1943).

O

OEt

EtO2C-CO2Et

H2SO4

O

O

O

CO2Et

CO2EtO

+NaOEt

EtOH, Et2O

(73~81%)

E.B. Hershberg, L.F. Fieser, Org. Synth., Coll. Vol. 2, 194 (1943).

EtO2CCO2Et EtO C

O

C

O

OEtKOEt. Et2O

!

HO2C CO2H

O

!

EtO2C CO2Et

O

CO2Et

+

82~83%

HCl, H2O

75~77%

L. Friedman, E. Kosower,

Org. Synth., Coll. Vol. 3, 510 (1955).

!"#$%&'()*$%+,Org. Synth. Coll. Vol., 5, 687 (1973) -.#/

MeO

MeO

CO2Et

MeO

MeO

CO2Et

NaOEtMeO

MeO

CO2Et

O–

MeO

MeO

CO2H

+ HCO2Et–10 ˚C

H2SO4, H3PO4 1) NaOH

2) HCl

H.L. Holmes, L.W. Trevoy, Org. Synth., Coll. Vol. 3, 300 (1955).

40~43%

CH3

CO2Et

O

CH3

CO2Et

O– Na

+

!

PhCO2Et

O– Na

+

PhCO2Et

O

PhCO2Et

PhCO2Et

O– Na

+

Na, EtOH

+ CH3CO2Et

H2SO4, H2O

50~55%

S.M. McElvain, K.H. Weber,

Org. Synth., Coll. Vol. 3, 379 (1955).

2. H2SO4, H2O

!"#$%$"&'(

CO2Et

CO2Et

2

1. NaOEt EtOH, !

O

O

CO2Et

EtO2C

185 - 195 °C

H2O

O

O

A.T. Nielsen, W.R. Carpenter, Org. Synth., Coll. Vol. 5, 288 (1973).

CO2Et

CO2Et

O

CO2Et

1) Na, toluene 100~115 ˚C

2) AcOH, H2O 74~81%

P.S. Pinkney, Org. Synth., Coll. Vol. 2, 116 (1943).

N

CO2Et

CH2CO2EtHCl

NO

1) KOEt, EtOH

toluene, !

2) HCl, H2O, 0 ̊ C

H.U. Daeniker, C.A. Grob, Org. Synth., Coll. Vol. 5, 989 (1973).

CH3

O

OEt

ONaHCO3

!

O

O

CH3

O

OCH3

EtO

O

CH3

O

OCH3

O

EtO

O

CH3

O

O

–O

H3C

F. Arndt,

Org. Synth., Coll. Vol. 3, 231 (1955).

53%

H

O

H3C OEt

O

Na, EtOH (cat.)0 - 5 °C

O

OEt

!"#$%$&'()

+

C.S. Marvel, W.B. King, Org. Synth., Coll. Vol. 1, 252 (1941).

アルキル化

2) CH3Br (g)H2C(CO2CH2CH3)

1) CH3CH2ONa, EtOHCH3H(CO2CH2CH3) + NaBr

79-83%

Organic Syntheses, Coll. Vol. 2, 279.

CH3COCH2COCH3 + CH3I!"#$%&'

K2CO3CH3COCH(CH3)COCH3

75-77%

Organic Syntheses, Coll. Vol. 5, 785.

NaCH(CO2CH3)2CH3C(O)O Cl

!"#$#%&'(80 °CCH3C(O)O CH(CO2CH3)2

86-90%

Organic Syntheses, Coll. Vol. 8, 5.

BrCH2CH2CH2Br H2C(CO2CH2CH3)2+

CO2CH2CH3

CO2CH2CH3

CH3CH2ONa

!"#$%

60-65 °C

Organic Syntheses, Coll. Vol. 3, 213.

CH2(CO2CH2CH3)2+BrCH2CH2CH2Cl2 CH3CH2ONa

!"#$%&80°C

CO2CH2CH3

CO2CH2CH3

53-55%

NaBr+ NaCl+

Organic Syntheses, Coll. Vol. 4, 288.

Na, EtOH

!"#$%$"&'(

Ph Cl+

CO2Et

CO2Et!

Ph

CO2Et

CO2Et

Organic Syntheses, Coll. Vol. 3, p.705 (1955).

EtOH, !

!"#$%$"&'(

NaOEtCO2Et

CO2Et

+

CO2Et

CO2Et

Br

Organic Syntheses, Coll. Vol. 3, p.495 (1955).

CO2Et

CO2Et

+Br

Br

NaOH, 25 °C CO2H

CO2H !""#$%&'

Organic Syntheses, Coll. Vol. 7, p.411 (1990).

リチウムエノラート

H3C

O

H3C1. LDA, DME

-40 to 0 °C

!"#$%$"&'(

CH2Ph

O

2. PhCH2Br

Organic Syntheses, Coll. Vol. 6, p.121 (1988).

O

EtO

1 . LDA , THF , 78 °C

2 . CH3I , - 78 to 25 °C

O

CH3

EtO

!"#$%$"&'(

Organic Syntheses, Coll. Vol. 7, p. 208 (1990).

!"#$%

O

N Ph

O O

N

1. LDA THF, -78 °C

2. PhCOCl

Organic Syntheses, Coll. Vol. 8, p.326 (1993).

n-C8H17CH2CO2Et1. LDA, THF, -78 °C

2. Ph2MeSiCl

CH CO2Et

SiMePh2

n-C8H17 !"#$%$"&'(

Organic Syntheses, Coll. Vol. 8, p.474 (1993).

エナミンとイミン（アザエノラート）

O

NH

N O

CH2CH=CH21) CH2=CHCH2Br

2) H2O

66% G. Stork, A. Brizzolara, H. Landesman, J. Szmuszkovicz, R. Terrell,

J. Am. Chem. Soc., 85, 207 (1963).

O

CH3 NH

N

CH3

ICH2CH=CCH3

CO2C(CH3)3 CH3

O

CH2CH=CCH3

CO2H2) H3O+ / H2O

1)

52% P.L. Stotter, K.A. Hill, J. Am. Chem. Soc., 96, 6524 (1974).

(CH3)2CHCH OK2CO3

t-BuNH2

CH NC(CH3)3(CH3)2C

CH2Ph

(CH3)2CHCH N–t-BuTHF

EtMgBr

CH O(CH3)2C

CH2Ph

(CH3)2C CH N

t-Bu

MgBr

1) PhCH2Cl

2) H2O63~66%

10% HCl / H2O

G. Stork, S.R. Dowd, Org. Synth., Coll. Vol. 6, 526 (1988).

O

Me2N–N

Na

TsOH

H2N–NMe2

Me2N–N

O

(CH2)3CH3

NaH

(Me2N)3PO

1) CH3(CH2)3Br

benzene, refluxtoluene, reflux

2) AcOH, NaoAc, H2O

65~72% G. Stork, S.R. Dowd, Org. Synth., Coll. Vol. 6, 242 (1988).

O

N

OMe

NH2

NN

HOMe

SAMP

O

NN

HOMe

O3

+1) LDA, Et2O, 0 ˚C

2) CH3CH2CH2I, –110 ˚C

CH2Cl2, –78 ̊ C56~58% yield (97% ee)

D. Enders, H. Kipphardt, P. Fey, Org. Synth., Coll. Vol. 8, 403 (1993).

エノールシリルエーテル

O OSiMe3

Cl

TiCl4, CH2Cl2

OMe3SiCl, Et3N

DMF, reflux

17 h 60~62% –50 ˚C, 2.5 h60~62%

M.T. Reetz, I. Chatziiosifidis, F. Hübner, H. Heimbach, Org. Synth., Coll. Vol. 7, 424 (1990). ニトリルの縮合反応

S. A. DiBiase, J. R. Beadle, G. W. Gokel, Org. Synth., Vol. 62, 179 (1984).

80-83%

reflux, 2 h

CH3CN

KOHO

CN

PhCHO

reflux

CH3CN

KOHPh

CN 31-45%