アザクライゼン転位とその周辺

発想と展開

抄録

The Ireland-Claisen rearrangement of the enolates of allyl esters, frequently used for the stereocontrolled C-C bond formation, is not suited for the substrate-controlled asymmetric induction. In order to cover the shortcoming, we investigated the thermal rearrangement of amide enolates and found the 1) the enolate derived from N- (2 E) -butenyl-N-butylpropanamide rearranged with excellent internal asymmetric induction (syn : anti= 199 : 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 a-position. Utilyzing the reaction, (-) -verrucarinolactone, D-allo-isoleucine, and (-) -isoiridomyrmecin were synthesized with excellent stereoselectivity in short steps. Through the study, an efficinet, mild and versatile method for the hydrolysis of N-monosubstituted carboxamides, and N, N, N′, N′-tetramethylazodicarboxamide (TMAD) -Bu₃P, a new reagent system applicable to the Mitsunobu reaction of Brønsted acid of pK_α up to 13.5 were developed. The latter provides an efficient general method for the preparation of allylic secondary amines.