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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Stereochemical Outcomes in Reductive Cyclizations To Form Spirocyclic Heterocycles
Matthew A Perry1, Richard R Hill1, Justin J Leong1
1Department of Chemistry, University of California, Irvine, 1102 Natural Sciences II Irvine, California 92697, United States.
Abstract:
Reductive lithiation and cyclization of N-Boc α-amino nitriles are often highly stereoselective. The alkyllithium intermediates are formed with varying levels of selectivity, but the alkyllithium geometry does not play a major role in the overall stereoselectivity. The final configuration is determined in the cyclization reaction, where both retention and inversion pathways are observed. Where strong thermodynamic preferences exist in the products, the kinetically controlled alkyllithium cyclization favors the more stable product.
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