Copper-catalysed, Stereoconvergent, Cis-diastereoselective Borylative Cyclisation Of ω-methanesulfonate-functionalised α,β-unsaturated Esters And Ketones

Five- and six-membered carbocycles are common motifs in both natural and synthetic compounds that exhibit important biological and pharmaceutical activities. The development of novel methods for the construction of carbocycles via carbon?carbon bond formation is therefore of great importance in synthetic organic chemistry. In such methods, organoboron compounds are important building blocks for the stereoselective preparation of a wide range of organic molecules due to their versatility for derivatization. The reported synthetic route to cycloalkylboron compounds involves the hydroboration of cycloalkene derivatives and the hydrogenation of cycloalkenylboronates. We envisioned that ω-functionalisation of these compounds could provide a novel route to cycloalkylboronates bearing a neighbouring electron-withdrawing group(EWG). β-Boryl-substituted cycloalkane is a potential synthetic intermediate for cyclic β-amino acids. Cyclic β-amino acids exhibit important biological activities, whose stereoconvergent synthetic method has not been reported thus far.In recent years, the diastereoselective intramolecular borylative cyclisation of ω-functionalised α,β-unsaturated aromatic and silyl compounds is being increasingly utilised to synthesise cyclopropyl and cyclobutylboronates. This paper is to synthesize cyclopentyl and cyclohexyl boronic esters through the copper-catalyst borylative cyclisation of ω-methanesulfonate-functionalised α,β-unsaturated esters and ketones. The experiment results are as follows:(1) Cu Cl/phosphine is the effective catalyst in the reaction. This reaction provides a route to cis-β-ester- and carbonyl- substituted five- and six-membered boronic esters.(2) The reaction is highly stereoconvergent. The reaction leads to the formation of cis- or trans- five- and six-membered boron-substituted carbocycles with excellent cis-selectivity(cis:trans > 99:1).(3) The reaction shows good compatibility of ester f unctional group. The substrate can bear a methyl group at the α-position or ω-position. This method was also used to synthesize the nitrogen-heterocycle and oxygen-heterocycle.(4) Four derivatives of five-membered borate ester were obtained.(5) Fifteen substrates of methyl sulfonic acid unsaturated esters have been synthesized in the experiment, among them twelves are un-reported compounds.