The intramolecular aldol condensation route to fused bi- and tricyclic beta-lactams

被引:30
作者
Alcaide, B
Polanco, C
Saez, E
Sierra, MA
机构
[1] Depto. de Quim. Orgánica I, Facultad de Química, Universidad Complutense
关键词
D O I
10.1021/jo960904w
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Staudinger cycloaddition of activated acid chlorides to 1,3-ketoaldimines, prepared in quantitative yields from 1,3-ketoaldehydes and amino esters, gave in excellent yields cis-a-azetidinones, 6-8, having the adequate functionality to obtain fused bi- and tricyclic beta-lactams. Reaction of compounds 6 with LHMDS at low temperature gave a single diastereomer of fused bicyclic compounds with a carbapenam or carbacefam skeleton. Treatment of diastereomeric cis-2-azetidinones, 7/8, in analogous conditions resulted either in the exclusive cyclization of one of the two diastereomers to form tricyclic [4.n.m] (n = 5, 6; m = 5, 6) compounds, or in the cyclization of both diastereomers to form tricyclic [4.n.7] (n = 5, 6) 2-azetidinones. In all cases the cyclization step was totally stereoselective. Alternatively, trans-carbapenams and one example of a tricyclic system having a trans-2-azetidinone ring have been obtained by using longer reaction times and higher temperatures. Epimerization at C3 of the 2-azetidinone nucleus occurs in these reaction conditions to obtain a single diastereomer of the final products. This approach to fused policyclic 2-azetidinones is one of the scarce syntheses of this kind of compound making use of the aldol condensation.
引用
收藏
页码:7125 / 7132
页数:8
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