Issue 34, 2012
From the journal:

Organic & Biomolecular Chemistry

Enantioselective, protecting group-free synthesis of 1S-ethyl-4-substituted quinolizidines†

Mercedes Amat,*a   Vladislav Semak,a   Carmen Escolano,*a   Elies Molinsb  and  Joan Boscha  

* Corresponding authors

a Laboratory of Organic Chemistry, Faculty of Pharmacy, and Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain
E-mail: cescolano@ub.edu, amat@ub.edu;
Fax: +34-93-402-4539

b Institut de Ciència de Materials de Barcelona (CSIC), Campus UAB, 08193 Cerdanyola, Spain

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.

Graphical abstract: Enantioselective, protecting group-free synthesis of 1S-ethyl-4-substituted quinolizidines

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Article information

DOI
https://doi.org/10.1039/C2OB25392E
Article type
Paper
Submitted
23 Feb 2012
Accepted
30 Mar 2012
First published
23 Jul 2012

Org. Biomol. Chem., 2012,10, 6866-6875

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Enantioselective, protecting group-free synthesis of 1S-ethyl-4-substituted quinolizidines

M. Amat, V. Semak, C. Escolano, E. Molins and J. Bosch, Org. Biomol. Chem., 2012, 10, 6866 DOI: 10.1039/C2OB25392E

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