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. 2025 Oct 3;27(39):11065-11070.
doi: 10.1021/acs.orglett.5c03430. Epub 2025 Sep 22.

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

Rubén Miguélez  1 , Omar Arto  1 , Hannah Siera  2 , Jan Schulte  2 , Isabel Merino  3 , Gebhard Haberhauer  2 , Pablo Barrio  1
Affiliations

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

Rubén Miguélez et al. Org Lett. .

Abstract

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.

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Figures

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Complete mapping of conformational effects.
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1. Complete Mapping of Conformational Effects a
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2. Complete Mapping of Conformational Effects a
See this image and copyright information in PMC

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