A three-step procedure for the synthesis of multifunctionalized
heterocycles from a pyroglutamic
acid derivative,
glycidyl components and anilines by nucleophilic substitution and cobalt catalysis is presented.
Recently we investigated the formation of 5- and 6-membered heterocycles from ethyl acetoacetate and glycidyl derivatives such as epichlorohydrin.<1> We found that the selectivity of this reaction was strongly influenced by the solvent and by the base applied, and especially by the nature of the leaving group at the glycidyl derivative. Despite the preparative potential of analogous cyclization reactions with other
ambident nucleophiles, reports on this subject are surprisingly rare.<2>
For instance,
amino acids and their derivatives 1 should be suitable as ambident nucleophiles. In principle the reaction with glycidyl derivatives 2 should lead to morpholinones 3 as depicted in Scheme 1, a class of heterocycles that are interesting as a crucial moiety of drugs for the treatment of various inflammatory and other diseases.<3-5>.
Beilstein Journal of Organic Chemistry 2007, 3:28
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