Towards improving enantioselectivity of γ- alkylated linear α,β-unsaturated aldehydes
Source
Indian Institute of Technology, Gandhinagar
Date Issued
2016-01-01
Author(s)
Srivastava, Ravi
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.
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.