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

Juan A. Sirvent, Bayer Pharma AG, Drug Discovery Palladium-Catalyzed Direct α-Arylation of p-Methoxybenzyl-Protected S,S-Dimethylsulfoximine 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)arylsubstituted 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. For details: Palladium-Catalyzed Direct α-Arylation of p-Methoxybenzyl-Protected S,S-Dimethylsulfoximine Juan A. Sirvent (a), Donald Bierer (b), Robert Webster (b), Ulrich Lücking (a) a. Bayer Pharma AG, Drug Discovery, Müllerstr. 178, 13353 Berlin, Germany b. Bayer Pharma AG, Drug Discovery, Aprather Weg 18a, 42113 Wuppertal, Germany DOI: 10.1055/s-0036-1588894; Art ID: ss-2016-t0534-op For more information about the solution applied: https://www.chemspeed.com/ISYNTH https://www.chemspeed.com/SWILE For details please contact [email protected]