Diastereoselective zwitterionic aza-Claisen rearrangement: The synthesis of bicyclic tetrahydrofurans and a total synthesis of (+)-dihydrocanadensolide

The zwitterionic Claisen rearrangement of optically-active N-allyl pyrrolidines and various acid chlorides proceeds with high simple diastereoselection (internal asymmetric induction) and high 1,2-asymmetric induction, generating a new C-C bond adjacent to a chiral C-O function. resulting gamma,delta-unsaturated amides were cyclized to the corresponding optically active gamma-butyrolactones, which are useful intermediates in natural product synthesis. On one hand, a diastereoselective iodocyclization of several lactones led to tetrahydrofurans with a substitution pattern representing a key intermediate of an oxa-prostaglandin synthesis. procedure of a Swern oxidation and consecutive Grignard reaction of one gamma-lactone allowed a diastereoselective chain elongation. The final oxidation/cyclization sequence completed a highly efficient synthesis of the (+)-dihydrocanadensclide or its C-3 epimer, respectively.