A versatile approach to functionalized cyclic ketones bearing quaternary carbon stereocenters via organocatalytic asymmetric conjugate addition of nitroalkanes to cyclic β-substituted α,β-Enones

A versatile organocatalytic asymmetric conjugate addition of nitroalkanes to beta-substituted cyclic alpha,beta-enones to yield cyclic ketones bearing all-carbon quaternary stereogenic centers at beta-C has been developed. This is an extension of the method that we developed during the total synthesis of (-)-haliclonin A, which features the employment of structurally relatively simple, cheap and easily available primary amine-thiourea derived from (R,R)-1,2-diaminocyclohexane as the chiral catalyst. The method shows wide substrate scope, good functional group tolerance, which allows a quick access to multi-functionalized chiral compounds. The synthetic potential of the method was demonstrated by one-step transformations of the nitro-ketone adducts to four other classes of compounds. The absolute configurations of adducts were determined by comparison of both the retention time of chiral HPLC analysis and sense of specific optical rotation with those of a known compound. The enantioselective control mechanism was rationalized based on the DFT computational studies. (c) 2021 Elsevier Ltd. All rights reserved.

Automated summary

A versatile organocatalytic asymmetric conjugate addition of nitroalkanes to beta-substituted cyclic alpha,beta-enones has been developed, yielding cyclic ketones with all-carbon quaternary stereogenic centers. The method shows wide substrate scope and good functional group tolerance, allowing quick access to multi-functionalized chiral compounds. The synthetic potential of the method was demonstrated by one-step transformations of the nitro-ketone adducts to other classes of compounds.