Decarboxylative Photocyclization:  Synthesis of Benzopyrrolizidines and Macrocyclic Lactones

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