Decarboxylative Photocyclization: Synthesis of Benzopyrrolizidines and Macrocyclic Lactones.

Abstract

The benzopyrrolizidines 2, 6a, and 6b were synthesized from the enantiomerically pure γ-amino acid derivatives 1, 5a, and 5b by decarboxylative photocyclization of the corresponding potassium salts in aqueous acetone. The diastereoselectivity of the radical coupling step was low (dr = 60:40) for the N-phthaloylglutamic acid methyl ester 1, whereas the α-benzyl- and the α-methyl-substituted γ-phthalimido butyric acid derivatives 5a,b cyclized with high cis diastereoselectivity (dr = 91:9 and 97:3, respectively). Acid-catalyzed epimerization of the cis/trans-2 mixture gave exclusively cis-2. The benzopyrrolizidines cis/trans-2 mixture was transformed with high stereoselectivity (dr = 93:7, ee >98%) into the cis methyl ether 3 via the corresponding acyliminium cation and subsequently into the allyl derivative 4 (dr = 86:14) with trimethylallylsilane catalyzed by titanium tetrachloride. The structures of the benzopyrrolizidines rac-3, (+)-3, rac-4, and 6a were determined by X-ray structure analyses. The macrocyclic lactones 8a,b were formed in high yields from the precursors 7a,b. The diastereoselectivity for the valine-derived substrate (in contrast to the reactions of 5a and 5b) was only moderate (dr = 64:36). The structure of the macrolide 9a (from 8a) was determined by X-ray structure analysis.