Catalyst Evolution in Ruthenium-Catalyzed Coupling of Amines and Alcohols

We describe the mechanism, scope, and catalyst evolution
for our
ruthenium-based coupling of amines and alcohols, which proceeds from
a [(η6-cymene)­RuCl­(PyCH2PtBu2)]­OTf (1) precatalyst.
The method selectively produces secondary amines through a hydrogen
borrowing mechanism and is successfully applied to several heterocyclic
carbinol substrates. Under the reaction conditions, precatalyst 1 evolves through a series of catalytic intermediates: [(η6-cymene)­RuH­(PyCH2PtBu2)]­OTf (3), [Ru3H2Cl2(CO)­(PyCH2PtBu2)2{μ-(C5H3N)­CH2PtBu2}]­OTf (4), and a diastereomeric pair of [Ru2HCl­(CO)2(PyCH2PtBu2)2(μ-O2CnPr)]­X
(trans-5, X = Cl; cis-6, X = OTf). The structures of 4 and 6 were established by single-crystal X-ray diffraction. A
study of catalytic activity shows that 4 is a dormant
(but alive) form of the catalyst, whereas 5 and 6 are the ultimate dead forms. Electrochemical studies show
that 4 is redox active and undergoes electrochemically
reversible one-electron oxidation at E1/2 = 0.442 V (vs Fc+/Fc) in CH2Cl2 solution. We discuss the factors that govern the formation of 3–6 and the role of selective ruthenium
carbonylation, which is essential for enabling generation of the active
catalyst. We also connect these discoveries to the identification
of conditions for amination of aliphatic alcohols, which eluded us
until we understood the catalyst’s complex speciation behavior.