Three‐Component Difunctionalization of Cyclohexenyl Triflates: Direct Access to Versatile Cyclohexenes via Cyclohexynes

Abstract

Difunctionalization of strained cyclic alkynes presents a powerful strategy to build richly functionalized cyclic alkenes in an expedient fashion. Herein we disclose an efficient and flexible approach to achieve carbohalogenation, dicarbofunctionalization, aminohalogenation and aminocarbonation of readily available cyclohexenyl triflates. We have demonstrated the novel use of zincate base/nucleophile system for effective formation of key cyclohexyne intermediates and selective addition of various carbon and nitrogen nucleophiles. Importantly, leveraging the resulting organozincates enables the incorporation of a broad range of electrophilic partners to deliver structurally diverse cyclohexene motifs. The importance and utility of this method is also exemplified by the modularity of this approach and the ease in which even highly complex polycyclic scaffolds can be accessed in one step.

The Stannum–Ene Reactions of Benzyne and Cyclohexyne with Superb Chemoselectivity for Cyclohexyne

“…Very recently, Wang et al. developed a convenient approach to access substituted cycloalkenes from cyclohexenyl triflates [3o] . These achievements greatly promote the advance of cyclohexyne chemistry, making it an attractive building block with useful potential applications.…”

Catalytic Asymmetric Synthesis of Zinc Metallacycles

“…The zinc metallacycles generated in this reaction serve as versatile intermediates for the synthesis of allylic amines containing trisubstituted alkenes (Figure ). For example, quenching of the reaction with I 2 or N -bromosuccinimide (NBS) instead of HCl­(aq) yielded halogenated products 36 and 37 , respectively. Related chalcogenation reactions were carried out with PhSeSePh or PhSSPh (products 38 and 39 ).…”