Asymmetric Synthesis of Nortropanes via Rh-Catalyzed Allylic Arylation

Authors

Yan Zhang
F Wieland Goetzke
Kirsten E Christensen
Stephen P Fletcher

Language

English

Publication Date

8-5-2022

Journal

ACS Catalysis

DOI

10.1021/acscatal.2c02259

PMID

35966601

PMCID

PMC9361292

PubMedCentral® Posted Date

July 2022

PubMedCentral® Full Text Version

Post-print

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.

Keywords

alkaloids, asymmetric catalysis, bicycles, rhodium, Suzuki−Miyaura coupling, kinetic resolution

Published Open-Access

yes

Recommended Citation

Zhang, Yan; Goetzke, F Wieland; Christensen, Kirsten E; et al., "Asymmetric Synthesis of Nortropanes via Rh-Catalyzed Allylic Arylation" (2022). Faculty, Staff and Student Publications. 1625.
https://digitalcommons.library.tmc.edu/uthmed_docs/1625