Sodium Bicyclo[1.1.1]pentanesulfinate: A Bench‐Stable Precursor for Bicyclo[1.1.1]pentylsulfones and Bicyclo‐ [1.1.1]pentanesulfonamides

• Published in: Chemistry : a European journal Vol. 26; no. 19; pp. 4242 - 4245
• Main Authors: Bär, Robin M., Gross, Patrick J., Nieger, Martin, Bräse, Stefan
• Format: Journal Article
• Language: English
• Published: Germany John Wiley and Sons Inc 01-04-2020
• Subjects: bicyclo[1.1.1]pentane; bioisosteres; Communication; Communications; propellanes; sulfonamides; sulfur; sulfur; sulfonamides; bioisosteres; bicyclo[1.1.1]pentane; propellanes
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202000097

Herein, we present the synthesis of the bench‐stable sodium bicyclo[1.1.1]pentanesulfinate (BCP‐SO2Na) and its application in the synthesis of bicyclo[1.1.1]pentyl (BCP) sulfones and sulfonamides. The salt can be obtained in a four‐step procedure from commercially available precursors in multigram scale without the need for column chromatography or crystallization. Sulfinates are known to be useful precursors in radical and nucleophilic reactions and are widely used in medicinal chemistry. This building block enables access to BCP sulfones and sulfonamides avoiding the volatile [1.1.1]propellane which is favorable for the extension of SAR studies. Further, BCP‐SO2Na enables the synthesis of products that were not available with previous methods. A chlorination of BCP‐SO2Na and subsequent reaction with a Grignard reagent provides a new route to BCP sulfoxides. Several products were analyzed by single‐crystal X‐ray diffraction.
Scaling the chemical heights! We present a scalable synthesis of the bench‐stable sodium bicyclo[1.1.1]pentane sulfinate (BCP‐SO2Na) in four steps without the need of chromatography or crystallization. Further, its application in the synthesis of BCP sulfones and sulfonamides is described (see scheme).