Enantioselective Au(I)-Catalyzed Multicomponent Annulation via Tethered Counterion-Directed Catalysis

Gold(I) complexes of a new 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 the first example of highly enantioselective multicomponent reaction in gold(I) catalysis. The reactions proceed at low catalyst loading, 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, as well as to yne-enone derived oximes. DFT calculations are reported that enlighten the enantiocontrol pathway.