Remote Functionalization by Pd-Catalyzed Isomerization of Alkynyl Alcohols

In recent years, progress has been made in the development
of catalytic
methods that allow remote functionalizations based on alkene isomerization.
In contrast, protocols based on alkyne isomerization are comparatively
rare. Herein, we report a general Pd-catalyzed long-range isomerization
of alkynyl alcohols. Starting from aryl-, heteroaryl-, or alkyl-substituted
precursors, the optimized system provides access preferentially to
the thermodynamically more stable α,β-unsaturated aldehydes
and is compatible with potentially sensitive functional groups. We
showed that the migration of both π-components of the carbon–carbon
triple bond can be sustained over several methylene units. Computational
investigations served to shed light on the key elementary steps responsible
for the reactivity and selectivity. These include an unorthodox phosphine-assisted
deprotonation rather than a more conventional β-hydride elimination
in the final tautomerization event.