The Mechanism of Rh(I)-Catalyzed Coupling of Benzotriazoles and Allenes Revisited: Substrate Inhibition, Proton Shuttling, and the Role of Cationic vs Neutral Species

Direct coupling of benzotriazole to unsaturated substrates
such
as allenes represents an atom-efficient method for the construction
of biologically and pharmaceutically interesting functional structures.
In this work, the mechanism of the N2-selective
Rh complex-catalyzed coupling of benzotriazoles to allenes was investigated
in depth using a combination of experimental and theoretical techniques.
Substrate coordination, inhibition, and catalyst deactivation was
probed in reactions of the neutral and cationic catalyst precursors
[Rh(μ-Cl)(DPEPhos)]2 and [Rh(DPEPhos)(MeOH)2]+ with benzotriazole and allene, giving coordination,
or coupling of the substrates. Formation of a rhodacycle, formed by
unprecedented 1,2-coupling of allenes, is responsible for catalyst
deactivation. Experimental and computational data suggest that cationic
species, formed either by abstraction of the chloride ligand or used
directly, are relevant for catalysis. Isomerization of benzotriazole
and cleavage of its N–H bond are suggested to occur by counteranion-assisted
proton shuttling. This contrasts with a previously proposed scenario
in which oxidative N–H addition at Rh is one of the key steps.
Based on the mechanistic analysis, the catalytic coupling reaction
could be optimized, leading to lower reaction temperature and shorter
reaction times compared to the literature.