A Highly Active and Air-Stable Ruthenium Complex for the Ambient Temperature Anti-Markovnikov Reductive Hydration of Terminal Alkynes

The
conversion of terminal alkynes to functionalized products by
the direct addition of heteroatom-based nucleophiles is an important
aim in catalysis. We report the design, synthesis, and mechanistic
studies of the half-sandwich ruthenium complex 12, which
is a highly active catalyst for the anti-Markovnikov reductive hydration
of alkynes. The key design element of 12 involves a tridentate
nitrogen-based ligand that contains a hemilabile 3-(dimethylamino)­propyl
substituent. Under neutral conditions, the dimethylamino substituent
coordinates to the ruthenium center to generate an air-stable, 18-electron,
κ3-complex. Mechanistic studies show that the dimethylamino
substituent is partially dissociated from the ruthenium center (by protonation) in the reaction media, thereby generating a vacant coordination
site for catalysis. These studies also show that this substituent
increases hydrogenation activity by promoting activation
of the reductant. At least three catalytic cycles, involving the decarboxylation
of formic acid, hydration of the alkyne, and hydrogenation of the
intermediate aldehyde, operate concurrently in reactions mediated
by 12. A wide array of terminal alkynes are efficiently
processed to linear alcohols using as little as 2 mol % of 12 at ambient temperature, and the complex 12 is stable for
at least two weeks under air. The studies outlined herein establish 12 as the most active and practical catalyst for anti-Markovnikov
reductive hydration discovered to date, define the structural parameters
of 12 underlying its activity and stability, and delineate
design strategies for synthesis of other multifunctional catalysts.