Studies On The Asymmetric Reductive Oxy-Nazarov Cyclization

The Nazarov cyclization is a classic method in the construction of five-membered carbocycles. With the development of kinds of modified Nazarov reaction, those reactions have been widely used in the total synthesis of natural products. Compared with catalytic asymmetric Nazarov reaction, chiral auxiliary induced asymmetric Nazarov reaction is more environmental friendly with higher atom economy. Reductive oxy-Nazarov reaction(Scheme 1)is a novel 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.On the basis of the previous research, we studied the asymmetric reductive oxyNazarov reaction with C2-symmetric 1'-binaphthalene as chiral auxiliary(Scheme 2). Main experiment results are as follows(1)The absolute configuration of key intermediate(R)-2-49, which was synthesized from commercial available ?-methylnaphthalene, was determined by single-crystal X-ray diffraction. The synthesis process included Fe-catalyzed oxidative homo-coupling reaction and resolution with L-(+)-diethyl tartrate.(2)Aryl- and alkyl-substituted dioxolanone 2-50 were successfully synthesized by means of HWE reactions, and racemic 5-hydoxy cyclopentenones(R)-2-48 were obtained with high yields from the asymmetric reductive oxy-Nazarov reaction of those precursors.In conclusion, chiral dioxolanones(R)-2-50 can be achieved form the resolution of the racemic compound. As indicated from those preliminary results, there has no observable asymmetric induction from the reductive oxy-Nazarov reaction this type of chiral dioxolanones so far.