Towards improving enantioselectivity of γ- alkylated linear α,β-unsaturated aldehydes

Abstract

Selectively alkylating an alpha beta unsaturated aldehyde at gamma position has been a challenging task. It is very difficult to obtain high regio- as well as Enantio-selectivity at this place. A comprehensive amount of α product is also formed along with self condensation products. Earlier work has been done on selective γ alkylation of linear α,β-unsaturated unsaturated aldehydes. But in all those cases either alpha position has been blocked or both alpha and gamma position has been substituted to give desired ee and yield. Herein we present selective γ alkylation of linear α,β-unsaturated aldehyde without blocking the α position. We synthesized bulky proline derived catalyst to increase ee value and tested in our reaction. Although we observed good yield and ee value of the desired product in the beginning but unfortunately it did not furnished a higher level of dynamic kinetic resolution. Hence we focused ourselves towards synthesizing Thioxanthydrol derivatives of α, β- unsaturated aldehydes. We went on synthesizing Thioxanthydrol and Xanthydrol derivatives of α,β-unsaturated aldehydes. We faced a challenging task of synthesizing Xanthydrol derivative of enal as Xanthydrol cation was not forming under the reaction conditions. For this purpose, we proposed to synthesis tertiary alcohol by Grignard reaction. Although we observed by NMR spectroscopy that few peaks are matching with our desired compound, we were unable to isolate our desired product. So we thought of using cooperative catalysis between metals and organocatalyst. For this purpose, we used CuCl as Lewis acid and Diaryl Prolinol silylether as chiral catalyst. We showed that we were able to get desired compound using this system.