Palladium-Catalyzed Direct α-Arylation of p-Methoxybenzyl-Protected S,S-Dimethylsulfoximine

Juan A. Sirvent; Donald Bierer; Robert Webster; Ulrich Lücking

doi:10.1055/s-0036-1588894

Synthesis, Table of Contents

Synthesis 2017; 49(05): 1024-1036
DOI: 10.1055/s-0036-1588894

paper

Palladium-Catalyzed Direct α-Arylation of p-Methoxybenzyl-Protected S,S-Dimethylsulfoximine

Juan A. Sirvent

^aBayer Pharma AG, Drug Discovery, Müllerstr. 178, 13353 Berlin, Germany Email: ulrich.luecking@bayer.com

,

Donald Bierer

^bBayer Pharma AG, Drug Discovery, Aprather Weg 18a, 42113 Wuppertal, Germany

,

Robert Webster

^bBayer Pharma AG, Drug Discovery, Aprather Weg 18a, 42113 Wuppertal, Germany

,

Ulrich Lücking*

^aBayer Pharma AG, Drug Discovery, Müllerstr. 178, 13353 Berlin, Germany Email: ulrich.luecking@bayer.com

› Author Affiliations

Abstract

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Abstract

Sulfoximines have recently gained considerable recognition as an important structural motif in the life sciences. This is especially true for (hetero)aryl-substituted S,S-dimethylsulfoximine derivatives, such as the marketed insecticide sulfoxaflor, as well as the clinical candidates PTEFb inhibitor BAY 1143572 and ATR inhibitor AZD 6738 for the treatment of cancer. Herein, the first palladium-catalyzed direct α-arylation of p-methoxybenzyl-protected S,S-dimethylsulfoximine using readily available (hetero)aryl bromides is reported. This new method provides a safe, short, and efficient approach to (hetero)aryl-substituted S,S-dimethylsulfoximine derivatives, an important class of bioactive compounds, demonstrated by application of this methodology to an improved synthesis of PTEFb inhibitor BAY 1143572.

Key words

sulfoximines - palladium - cross-coupling - drug design - crop protecting agents

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References

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