Regio‐ and Stereoselective Synthesis of Ynenamides through Gold(I)‐Catalyzed Hydroalkynylation of Ynamides

Abstract

Transition metal catalysis is a useful tool for C−C bond‐forming reactions. Of special interest is the hydroalkynylation reaction of alkynes, which provides a simple method for the synthesis of enynes representing interesting structural motifs in organic chemistry. So far, there are only a few examples of gold(I)‐catalyzed hydroalkynylation reactions. Herein, we were able to show experimentally that the gold(I)‐catalyzed hydroalkynylation of ynamides leads regio‐ and stereoselectively to the corresponding ynenamides, a rather unknown type of molecule. A wide range of products could be generated with yields up to 90 % and, in contrast to many other gold‐catalyzed alkyne dimerization reactions, alkyl groups are tolerated. Quantum chemical calculations and NMR labelling experiments reveal a mechanism via dual gold catalysis.

Catalytic intermolecular hydrofunctionalizations of ynamides

“…Recently, Haberhauer and co-workers found that the stereoselectivity for hydroalkynylation of oxazolidinone-derived ynamides could be altered to anti -adducts when a bulky cationic gold catalyst JohnphosAuSbF 6 (DAC) was employed (Scheme 15). 41 A gold acetylide complex, pre-synthesized with phenylacetylene and DAC, was demonstrated to be a better catalyst for hydroalkynylation of oxazolidinone-derived ynamides. Based on this fact, it is believed that the terminal alkyne first reacts with the cationic gold complex to deliver the active catalyst gold acetylide intermediate Int-25 .…”