AZA-CLAISEN REARRANGEMENT - CONCEPTION AN D EVOLUTION

The Ireland-Claisen rearrangement of the enolates of allyl esters, fre quently used for the stereocontrolled C-C bond formation, is not suite d for the substrate-controlled asymmetric induction. In order to cover the shortcoming, we investigated the thermal rearrangement of amide e nolates and found the 1) the enolate derived from N-(2 E)-butenyl-N-bu tylpropanamide rearranged with excellent internal asymmetric induction (syn:anti = 19 : 1), that 2) the reaction of those containing chiral alkyl groups on the nitrogen proceeded with high selectivity(up to 19 : 1)in relative asymmetric induction, and that 3)the rearrangement can satisfactorily be extended to the acetamides with a heteroatom at the alpha-position. Utilizing the reaction, (-)-verrucarinolactone, D-all o-isoleucine, and (-)-isoiridomyrmecin were synthesized with excellent stereoselectivity in short steps. Through the study, an efficinet, mi ld and versatile method for the hydrolysis of N-monosubstituted carbox amides, and N, N, N', N'-tetramethylazodicarboxamide (TMAD)-Bu(3)P, a new reagent system applicable to the Mitsunobu reaction of Bronsted ac id of pK(a) up to 13.5 were developed. The latter provides an efficien t general method for the preparation of allylic secondary amines.