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Updated: May 20, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Enantioselective, protecting group-free synthesis of 1S-ethyl-4-substituted quinolizidines
Mercedes Amat1, Vladislav Semak, Carmen Escolano
1Laboratory of Organic Chemistry, Faculty of Pharmacy, Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain. amat@ub.edu
Abstract:
A practical enantioselective protecting group-free four-step route to the key quinolizidinone 6 from phenylglycinol-derived bicyclic lactam 1 is reported. The Grignard addition reaction to 6 takes place stereoselectively to give 1-ethyl-4-substituted quinolizidines 4-epi-207I and 7-9. Following a similar synthetic sequence, 9a-epi-6 is also accessed. However, the addition of Grignard reagents to 9a-epi-6 proceeds in a non-stereoselective manner. In order to gain insight into the different stereochemical outcome in the two series, theoretical calculations on the iminium salts A and B have been performed. The study concludes that the addition of the hydride, which is the step that determines the configuration of the final products, occurs in a stereoelectronic controlled manner. The theoretical study is in agreement with the experimental results.
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