2-Hydroxyindolizidine synthesis

Most of the oxoindolizidines have been prepared by Dieckmann reaction or related condensations. Thus (188) was used to prepare (189), which is a precursor for the synthesis of 2-methyl-1-hydroxyindolizidine (190) (70AP812). Ipalbidine (191a), which is one of the Ipomea group of alkaloids, was prepared as outlined in Scheme 26 (71HCA513). 

The intramolecular ene reaction has been utilized by Overman et al. in a synthesis of 6-alkylidene-8-hydroxyindolizidines (298). Treatment of the ketone precursors (297) with AlCl under the conditions shown gave the products (298) as an isomeric mixture about the double bond. Other Lewis acids were ineffective (e. g. BF2.0Et2) gave complex product mixtures (e.g. 

Batey has reported the first example of the reaction of alkenyl boronic acids and esters with activated N-acyliminium ion precursors under Lewis-acid catalysis giving 2-func-tionalized heterocydes in good yields [110]. This methodology has been further extended for the synthesis of fungal metabolite (lR, -8al )-l-hydroxyindolizidine (136) by concomitant deprotection and tosylation of the adduct followed by hydrogenation and cyclization in the presence of a palladium catalyst (Scheme 3.72). 

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