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Updated: Jun 23, 2026

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides
Published on: May 26, 2019
Highly diastereoselective formal nucleophilic substitution of bromocyclopropanes
Bassam K Alnasleh1, William M Sherrill, Marina Rubina
1Department of Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045-75832, USA.
Abstract:
A highly diastereoselective formal nucleophilic substitution of bromocyclopropanes with oxygen- and nitrogen-based nucleophiles was demonstrated. The reaction proceeds via a base-assisted dehydrohalogenation producing a cyclopropene intermediate, which subsequently undergoes addition of a pronucleophile across the strained double bond. Very high chemoselectivity toward addition of primary and secondary alkoxides, as well as N-nucleophiles, in the presence of tert-butoxide base was observed, whereas phenoxides did not undergo addition under these reaction conditions. Facial selectivity of the addition can be efficiently controlled either by sterics or through a directing effect of an amide, carboxylate, and an o-aminomethylphenol function. Employment of tethered optically active amino alcohols as pronucleophiles allowed for efficient assembly of homochiral bicyclic compounds.
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