Decarboxylative Photocyclization: Synthesis of Benzopyrrolizidines and Macrocyclic Lactones

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.