Studies On The Asymmetric Reductive Oxy-nazarov Cyclization Induced By A Novel Chiral Auxiliary

Reductive oxy-Nazarov(RON)reaction is a facile variant of the classic Nazarov cyclization developed in our laboratory previously,which represents a useful new synthetic method for the synthesis of 5-hydroxyl cyclopentenone scaffold in natural product synthesis.Based on the systematical research,a general protocol of an asymmetric RON reaction was designed and developed with the introduction of C2-symmetric diol as chiral auxiliary(Scheme 1).Scheme 1 Asymmetric RON cyclization reactionTo further understand the nature,expand the applicability,as well as enrich the method of the RON cyclization reaction,we studied herein the asymmetric reductive oxy-Nazarov reaction with C2-symmetric diol as chiral auxiliary(Scheme 2).The results show that the E-precursors with chiral 2,4-pentanediol can efficiently and rapidly undergo the reductive cyclization to afford the separable spiro ketal intermediate with a good dr.Moreover,the optically pure 5-hydroxy 2-cyclopentenone product can be obtained by subsequent hydrolysis reaction.2-352-48 Scheme 2 Asymmetric RON cyclization reaction induced by a novel chiral auxiliaryMeanwhile an effective approach to 1,4-dioxocan-2-one bearing binaphthalene skeleton was reported(Scheme 3).The synthetic process,including mono-esterification of BINOL?diazo-reaction and Cu(II)-catalyzed O-H insertion reaction,provided a facile and convenient route to synthesize compound 2-60.Moreover,the synthesis of chiral Horner-Wadsworth-Emmons reagent(R)-2-60 has been achieved from(R)-BINOL,which could be used as a novel chiral auxiliary for the asymmetric reductive oxy-Nazarov reaction.Scheme.3 Retrosynthetic anlysis of compound(R)-2-60...