Asymmetric Synthesis of Chiral Sulfoximines through the S‐Alkylation of Sulfinamides

Innovation in drug discovery critically depends on the development of new bioisosteric groups. Chiral sulfoximines, which contain a tetrasubstituted sulfur atom that bears one nitrogen, one oxygen, and two different carbon substituents, represent an emerging chiral bioisostere in medicinal chemistry...

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Bibliographic Details
Published in:Angewandte Chemie 2019-12, Vol.131 (49), p.17825-17829
Main Authors: Aota, Yusuke, Kano, Taichi, Maruoka, Keiji
Format: Article
Language:English
Subjects:
Alkylation
Alkylierungen
Asymmetric synthesis
Asymmetrische Synthese
Asymmetry
Chemistry
Chiralität
Modularity
Organic chemistry
Reagents
Substructures
Sulfinamide
Sulfoxides
Sulfoximine
Sulfur
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Summary:Innovation in drug discovery critically depends on the development of new bioisosteric groups. Chiral sulfoximines, which contain a tetrasubstituted sulfur atom that bears one nitrogen, one oxygen, and two different carbon substituents, represent an emerging chiral bioisostere in medicinal chemistry. Chiral sulfoximines are conventionally prepared by a stereospecific nitrene transfer reaction to chiral sulfoxides; however, the number of readily available chiral sulfoxides remains limited. Herein, we report the asymmetric synthesis of a class of hitherto difficult‐to‐access chiral sulfoximines with two structurally similar alkyl chains. Our synthetic approach is based on the sulfur‐selective alkylation of easily accessible chiral sulfinamides with commercially available reagents under simple and safe conditions. This stereospecific S‐alkylation offers a general and scalable approach to the asymmetric synthesis of chiral sulfoximines, which represent important substructures in bioactive molecules. Chirale Sulfoximine wurden durch eine ungewöhnliche Schwefel‐selektive Alkylierung von leicht zugänglichen Sulfinamiden mit Alkylhalogeniden unter basischen Bedingungen synthetisiert. Zudem wurden verschiedene chirale Sulfinamide aus den chiralen Sulfoximinen (R1=tert‐Butyl) durch die Entfernung der tert‐Butyl‐Gruppe mit Säure erhalten.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201911021