Synlett 2024; 35(09): 1023-1027
DOI: 10.1055/a-2210-0893
cluster
Chemical Synthesis and Catalysis in Germany

A Novel Route towards Bicyclo[1.1.1]pentane Sulfoxides from a Bench-Stable Starting Material

Lukas S. Langer
a   Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany
,
Mareen Stahlberger
a   Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany
,
Robin M. Bär
a   Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany
,
Stefan Bräse  ∗
a   Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany
b   Institute of Biological and Chemical Systems - Functional Molecular Systems (IBCS-FMS), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany
› Author AffiliationsThe authors acknowledge support from the Deutsche Forschungsgemeinschaft (DFG) under Germany’s Excellence Strategy - 3DMM2O (EXC-2082/1-390761711).
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Abstract

Bicyclopentanes (BCPs) are non-classical bioisosteres that have gained a lot of interest in drug discovery as non-conjugated rigid hydrocarbons. There has been substantial progress in the synthesis of carbon- and nitrogen-substituted derivatives using [1.1.1]propellane as a precursor, while sulfur-substituted BCPs are rather underdeveloped. This work investigates a new method for the synthesis of BCP-sulfoxides. Herein, a previously reported bench-stable sodium BCP-sulfinate precursor is converted, using a range of aryl and alkyl magnesium bromides, into unsymmetrical BCP-sulfoxides via a convenient one-pot procedure. Furthermore, the conversion of the obtained sulfoxides into sulfoximines is explored.

Key words

bicyclo[1.1.1]pentane - sulfoxide - sulfoximine - bioisostere - one-pot - Grignard reagent

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2210-0893.
  • Supporting Information

Primary Data

    Primary data can be cited using the following DOI: 10.14272/collection/LL_2023-07-25_6

  • Primary Data


Publication History

Received: 19 September 2023

Accepted after revision: 13 November 2023

Accepted Manuscript online:
13 November 2023

Article published online:
15 December 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
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