Synergistic Gold(I)/Trimethylsilyl Catalysis: Efficient Alkynylation of N,O‐Acetals and Related Pro‐Electrophiles.

We report a unique mechanism-guided re- action that enhances and expands the chemical space that readily generated gold(I) acetylides currently operate in. Our strategy exploits the propensity of gold(I) carbophilic catalysts with specific counteran- ions (LAuX - X=triflate or triflimidate) to efficient- ly activate and desilylate trimethylsilylalkynes, there- by mediating the in situ formation of equal and cata- lytic quantities of a silyl Lewis acid (TMSX) of tuna- ble strength and a nucleophilic gold(I) acetylide. This unprecedented manifold opens avenues for de- veloping synergistic silyl-gold(I)-catalyzed alkynyla- tion strategies of diverse pro-electrophiles which were heretofore unattainable, the proof of concept being principally exemplified herein with the first catalytic alkynylation of N,O-acetals. The reaction proceeds at low catalyst loading, employs mild reac- tion conditions, is easily scalable, and affords propar- gylic lactam products in good to excellent yields. Fur- thermore, it is fully amenable to a diverse array of structure and function substrates, and also expands to other pro-electrophiles beyond N,O-acetals. Con- trol experiments have been carried out that strongly support our dual reaction mechanism proposal which, furthermore, itself outlines an inextricable link between the strength of the ancillary silyl Lewis acid (TMSOTf versus TMSNTf2) and the coordinat- ing ability of the gold counter anion employed. This underlying feature of our system underscores its sig- nificant potential and flexibility, which indeed mani- fests with the demonstration that by carefully select- ing the gold counter ion, it is possible to manipulate the strength of the ancillary silyl Lewis acid so that it can be tailored to the ionizing ability of a particular pro-electrophile.