Enantioselective hydrolysis of 1-arylpropargylic esters by enzymatic kinetic resolution and dynamic kinetic resolution of 1-arylallylic esters

• Main Author: Nelson, Keegan Gregory
• Format: Thesis
• Language: English
• Published: University of Missouri - Kansas City 2013
• Subjects: Organic chemistry; Antarc*; Antarctica
• Online Access: http://pqdtopen.proquest.com/#viewpdf?dispub=1538847

Chiral 1-arylprop-2-en-1-ols and 1-arylprop-2-yn-1-ols are useful building blocks for modern pharmaceuticals. Previous work has found that enzyme catalysis is a potential new enantioselective synthetic route to the former. We found that Candida antarctica lipase is also an effective catalyst for kinetic resolution of various substituted 1 arylpropargylic acetates and haloacetates, affording the respective (R) -1 arylproargylic alcohols with high enantioselectivity (99-100% ee). By varying the substituents on both sides of the ester bond, we discovered that the deacylation of lipase is likely the rate-determining step for our catalytic system. A greater challenge is designing a dynamic kinetic resolution (DKR) system for such substrates, which combines a resolving catalyst (lipase) with a racemizing catalyst, and can potentially lead to quantitative conversion of a racemic substrate into an enantiopure product. We studied the efficacy of various transition-metal complexes for substrate racemization and will report our results for In and Cu compounds. While kinetic resolution has been performed on the 1-arylallylic acetates with excellent yield and enantioselectivity and the DKR regime has been designed, the resulting site-isolation system has required further testing and fine tuning. We have herein investigated the utilization of macroscale site-isolation as well as various factors including solvent, and acyl donor effects in order to optimize conditions of the system.