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Updated: Sep 1, 2025

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Asymmetric Synthesis of Nortropanes via Rh-Catalyzed Allylic Arylation
Yan Zhang1, F Wieland Goetzke1, Kirsten E Christensen1
1Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
Abstract:
Tropane derivatives are extensively used in medicine, but catalytic asymmetric methods for their synthesis are underexplored. Here, we report Rh-catalyzed asymmetric Suzuki-Miyaura-type cross-coupling reactions between a racemic N-Boc-nortropane-derived allylic chloride and (hetero)aryl boronic esters. The reaction proceeds via an unexpected kinetic resolution, and the resolved enantiopure allyl chloride can undergo highly enantiospecific reactions with N-, O-, and S-containing nucleophiles. The method was applied in a highly stereoselective formal synthesis of YZJ-1139(1), a potential insomnia treatment that recently completed Phase II clinical trials. Our report represents an asymmetric catalytic method for the synthesis of YZJ-1139(1) and related compounds.
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