Asymmetric synthesis of nortropanes via Rh-catalysed allylic arylation

19 April 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Tropane derivatives are extensively used in medicine, but catalytic asymmetric methods for their synthesis are underexplored. Here we report Rh-catalysed asymmetric Suzuki-Miyaura type crosscoupling 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 the first synthesis of YZJ-1139(1) and related compounds using asymmetric catalysis.


Kinetic resolution
Asymmetric Catalysis
Suzuki-Miyaura coupling

Supplementary materials

Supporting Information
Supporting Information for 'Asymmetric synthesis of nortropanes via Rh-catalysed allylic arylation'


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