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Strain-Release-Driven Homologation of Boronic Esters: Application to the Modular Synthesis of Azetidines

Alexander Fawcett, Amna Murtaza, Charlotte H. U. Gregson, Varinder K. Aggarwal*

*School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, United Kingdom, Email: v.aggarwalbristol.ac.uk

A. Fawcett, A. Murtaza, C. H. U. Gregson, V. K. Aggarwal, J. Am. Chem. Soc., 2019, 141, 4573-4578.

DOI: 10.1021/jacs.9b01513 (free Supporting Information)



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Abstract

The high ring strain associated with azabicyclo[1.1.0]butane enables a modular construction of azetidines via generation of azabicyclo[1.1.0]butyl lithium followed by trapping with a boronic ester, N-protonation, and 1,2-migration with cleavage of the central C-N bond to relieve ring strain. Further functionalisations of the N-H azetidine and the boronic ester are reported.

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reaction pathway



The azabicyclo[1.1.0]butyl lithium can also be generated directly from a dibromoalkylamine which avoids forming the sulfoxide by-product. This then obviates the need for the catch and release protocol which is used to separate the sulfoxide by-product.

Varinder K. Aggarwal, December 22, 2019


Key Words

Azetidines


ID: J48-Y2019