Direct Propargylic Substitution of Hydroxyl Groups in Propargylic Alcohols
Pp. 278-310 (33)
Min-Liang Yao and George W. Kabalka
Propargylic alcohols are valuable starting materials in organic syntheses due
to their ready availability. The presence of two functional groups, an alkyne unit and an
alcohol unit, provide great opportunities for further functionalization. Straightforward
substitution of the hydroxyl group with nucleophiles is highly desirable due to atomefficiency
and environmental concerns. Since the first report of a ruthenium-catalyzed
propargylic substitution reaction in 2000, a number of propargylic substitutions using
transition-metal catalysts along with Brønsted and Lewis acids have been achieved.
Reactions with a variety of carbon- and heteroatom-centered nucleophiles, both
intermolecular and intramolecular versions, have been reported. These reactions have
been successfully applied to the syntheses of substituted furans, pyrrols, indoles,
isoxazoles and natural products. Asymmetric propargylic substitution reactions have
also been achieved. With the intent of recycling the Lewis acid catalyst, ionic liquid
techniques have been examined in propargylic substitutions as well. In recent years,
propargylic substitution reactions using a combination catalytic system, either two
different transition metals or an organocatalyst and Lewis acid, have been developed.
This opens a new area of cooperative catalytic reactions that generate synthetic
transformations that cannot be achieved by a single catalyst. Notably, the replacement
of hydroxyl groups by stereodefined halovinyl and alkynyl moieties has been recently
achieved. In this chapter, a brief summary of these advances is provided.
Propargylic alcohol, propargylic substitution, propargylation,
propargylic cation, nucleophile, transition-metal, Lewis acid, Brønsted acid,
enantioselective, propargyl alkoxide, organoboron, boron halide, allenylidene,
Meyer–Schuster rearrangement, ionic liquid.
University of Tennessee, Knoxville, 37996-1600, TN, USA