Page 78 - Advanced Organic Chemistry Part B - Reactions & Synthesis

50 MgBr
(CH 3 ) 2 CHCH NC(CH 3 ) 3 EtMgBr (CH 3 ) 2 C CH N PhCH 2 Cl (CH 3 ) 2 C CH NC(CH 3 ) 3
CHAPTER 1 H 2 O
C(CH3)3
CH 2 Ph
Alkylation of Enolates
and Other Carbon H 3 O +
Nucleophiles
(CH 3 ) 2 CCH O
CH 2 Ph
80% overall yield
Ref. 112

CH CH C CH O
3
1) LDA
CH CH CH CH N
3
CH CH 2 CH 2 O CH 3
2) 3 O CH 3
ICH CH 2 O CH 3 CH 3 O CH 3
2
3) H O
2
Ref. 113
Ketone imine anions can also be alkylated. The prediction of the regioselectivity
of lithioenamine formation is somewhat more complex than for the case of kinetic
ketone enolate formation. One of the complicating factors is that there are two imine
stereoisomers, each of which can give rise to two regioisomeric imine anions. The
isomers in which the nitrogen substituent R’ is syn to the double bond are the more
stable. 114
R' R'
N N
C C
CH 2 R CH 2 R
CH 3 CH 3
R' R'
R' R'
–
Li + – N – +1 N Li + Li + – N
or N Li or
C C C C
HC CH 2 R CH 3 CH HC CH 2 R CH 3 CH
H R H R
For methyl ketimines good regiochemical control in favor of methyl deproton-

ation, regardless of imine stereochemistry, is observed using LDA at −78 C. With

larger N-substituents, deprotonation at 25 C occurs anti to the nitrogen substituent. 115
R' R' R' R'
–
N N Li + N Li + – N
LDA LDA
RCH CCH 3 RCH C CH 2 RCH 2 CCH R" RCH CCH R"
2
2
2
2
–78°C 0°C
112
G. Stork and S. R. Dowd, J. Am. Chem. Soc., 85, 2178 (1963).
113
T. Kametani, Y. Suzuki, H. Furuyama, and T. Honda, J. Org. Chem., 48, 31 (1983).
114 K. N. Houk, R. W. Stozier, N. G. Rondan, R. R. Frazier, and N. Chauqui-Ottermans, J. Am. Chem.
Soc., 102, 1426 (1980).
115
J. K. Smith, M. Newcomb, D. E. Bergbreiter, D. R. Williams, and A. I. Meyer, Tetrahedron Lett., 24,
3559 (1983); J. K. Smith, D. E. Bergbreiter, and M. Newcomb, J. Am. Chem. Soc., 105, 4396 (1983);
A. Hosomi, Y. Araki, and H. Sakurai, J. Am. Chem. Soc., 104, 2081 (1982).