Page 210 - Advanced Organic Chemistry Part B - Reactions & Synthesis

182 2.5.2. Nucleophilic Addition-Cyclization of -Haloesters

CHAPTER 2 The pattern of nucleophilic addition at a carbonyl group followed by
Reactions of Carbon intramolecular nucleophilic displacement of a leaving group present in the nucleophile
Nucleophiles with can also be recognized in a much older synthetic technique, the Darzens reaction. 290
Carbonyl Compounds
The first step in this reaction is addition of the enolate of the -haloester to the
carbonyl compound. The alkoxide oxygen formed in the addition then effects nucle-
ophilic attack, displacing the halide and forming an -epoxy ester (also called a
glycidic ester).
O O –
– O
2 2 5
2 2 5
2
R 2 C CHCO C H R C CHCO C H R C CHCO C H
2
2 2 5
Cl Cl
Scheme 2.22 shows some examples of the Darzens reaction.
Trimethylsilylepoxides can be prepared by an addition-cyclization process.
Reaction of chloromethyltrimethylsilane with sec-butyllithium at very low temperature
gives an -chloro lithium reagent that leads to an epoxide on reaction with an aldehyde
or ketone. 291
s-BuLi
Me SiCH Cl Me 3 SiCHCl
3
2
THF, –78°C
Li
Cl
Me SiCHCl + CH CH CH CHO CH CH CH CH CHSiMe 3 CH 3 CH CH CH CHSiMe 3
3
2
3
2
2
3
2
2
2
Li O – O
Scheme 2.22. Darzens Condensation Reaction
1 a KOC(Me) O
2 2 5
O + ClCH CO C H 3 CO C H
2
2 2 5
H
2 b
KOC(Me) O 83 – 95%
PhCH O + PhCHCO C H 3 H CO C H
2 2 5
2 2 5
Ph Ph 75%
3 c O Cl
C H5
KOC(Me) 3 CH 3 O CO C H Ph O CO 2 2
PhCCH + ClCHCO C H 2 2 5 +
2 2 5
3
Ph H CH 3 H
62%
4 d
(1:1 mixture of isomers)
1) LiHMDS
CH CH CHCO C H O
3
2 2 5
2
O CH 3 CO C H
2 2 5
Br CH
2) CH CCH 3 3 CH 2 CH 3
3
a. R. H. Hunt, L. J. Chinn, and W. S. Johnson, Org. Synth., IV, 459 (1963).
b. H. E. Zimmerman and L. Ahramjian, J. Am. Chem. Soc., 82, 5459 (1960).
c. F. W. Bachelor and R. K. Bansal, J. Org. Chem., 34, 3600 (1969).
d. R. F. Borch, Tetrahedron Lett., 3761 (1972).
290 M. S. Newman and B. J. Magerlein, Org. React., 5, 413 (1951).
291
C. Burford, F. Cooke, E. Ehlinger, and P. D. Magnus, J. Am. Chem. Soc., 99, 4536 (1977).