Conformational Effects in Intramolecular C(sp³)–H Bond Functionalization: Gold(I)-Catalyzed Cycloisomerization of Aliphatic 1-Bromoalkynes as Benchmark Reaction

The use of cyclohexane derivatives displaying all possible substitution patterns has allowed us to study the influence of the conformational effects in the recently reported gold(I)-catalyzed cycloisomerization reaction of aliphatic 1-bromoalkynes that entails an unusual functionalization of a nonactivated C(sp³)-H bond. Some clear trends in terms of reactivity, regio- and stereoselectivity may be drawn from the experimental results and, in most cases, rationalized using intuitive conformational analysis arguments (i.e., equatorial/axial preferences). Occasionally, some unexpected results were also obtained, but they have also found a rational explanation. DFT calculations have been used to help us understand the underlying effects that dictate the reactivity or selectivity differences.