A general, enantioselective synthesis of N-alkyl terminal aziridines and C2-functionalized azetidines via organocatalysis

Timothy J Senter; Matthew C O'Reilly; Katherine M Chong; Gary A Sulikowski; Craig W Lindsley

doi:10.1016/j.tetlet.2015.01.140

A general, enantioselective synthesis of N-alkyl terminal aziridines and C2-functionalized azetidines via organocatalysis

Tetrahedron Lett. 2015 Mar 4;56(10):1276-1279. doi: 10.1016/j.tetlet.2015.01.140.

Authors

Timothy J Senter¹, Matthew C O'Reilly¹, Katherine M Chong¹, Gary A Sulikowski¹, Craig W Lindsley²

Affiliations

¹ Department of Chemistry, Vanderbitl Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA.
² Department of Chemistry, Vanderbitl Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA; Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, 37232, USA.

Abstract

A short, high-yielding protocol involving the enantioselective α-chlorination of aldehydes has been developed for the enantioselective synthesis of C2-functionalized aziridines and N-alkyl terminal azetidines from a common intermediate. This methodology allows for the rapid preparation of functionalized aziridines in 50-73% overall yields and 88-94% ee, and azetidines in 22-32% overall yields and 84-92% ee. Moreover, we developed a scalable and cost-effective route to the key organocatalyst (54% overall yield, >95% dr).

Keywords: azetdine; aziridine; enantioselective; organocatalysis.

Grants and funding

U54 MH084659/MH/NIMH NIH HHS/United States