Enantioselective Au(I)-Catalyzed Multicomponent Annulations via Tethered Counterion-Directed Catalysis
Zhenhao Zhang, Nazarii Sabat, Gilles Frison, Angéla Marinetti, Xavier Guinchard
Abstract
Gold(I) complexes of a chiral phosphoric acid-functionalized phosphine of the CPA-Phos series enable the enantioselective multicomponent reactions between aldehydes, hydroxylamines and cyclic yne-enones, leading to 3,4-dihydro-1H-furo[3,4-d][1,2]oxazines. This represents a rare example of a highly enantioselective multicomponent reaction in gold(I) catalysis. The reactions proceed at a low catalyst loading and provide high yields, total diastereoselectivity, and enantiomeric excesses up to 99%. Silver-free conditions can be applied. The method has a very broad scope as it applies to both aliphatic and aromatic aldehydes and hydroxylamines, to a variety of cyclic yne-enones, and to yne-enone-derived oximes. DFT calculations complement this study to enlighten reactivity issues and mechanistic pathways.