| William H. Pearson, Berry & Associates, Inc, 2434 Bishop Circle East, Dexter, MI 48130, Patrick Stoy, Department of Chemistry, University of Michigan, 930 North University Ave, Ann Arbor, MI 48109-1055, and Yuan Mi, Genomics Institute, Novartis Research Foundation, 10675 John J. Hopkins Dr, San Diego, CA 92121. |
The 1-aza[n.3.0]bicycloalkane motif, including the pyrrolizidines and indolizidines, is broadly distributed among alkaloidal natural products. We have found that such structures can be rapidly formed via a one-pot, three- component reaction cascade of 1, 2 and dipolarophile 3 proceeding through nonstabilized azomethine ylides. When R2 is an alkyl group, cycloadducts containing a 2,5-trans-disubstituted pyrrolidine ring (e.g. 4) are favored. This method tolerates enolizable hydrogens on 1 and marks the first time the 1-aza[5.3.0]bicyclodecane (n=3) ring system has been constructed using an azomethine ylide cycloaddition. When the tributylstannyl group in 2 is replaced by a trimethylsilyl group, enolizable hydrogens on 1 are not tolerated. |