Experimental and DFT Studies Explain Solvent Control of C–H Activation and Product Selectivity in the Rh(III)-Catalyzed Formation of Neutral and Cationic Heterocycles

A range of novel heterocyclic cations
have been synthesized by
the Rh­(III)-catalyzed oxidative C–N and C–C coupling
of 1-phenylpyrazole, 2-phenylpyridine, and 2-vinylpyridine with alkynes
(4-octyne and diphenylacetylene). The reactions proceed via initial
C–H activation, alkyne insertion, and reductive coupling, and
all three of these steps are sensitive to the substrates involved
and the reaction conditions. Density functional theory (DFT) calculations
show that C–H activation can proceed via a heteroatom-directed
process that involves displacement of acetate by the neutral substrate
to form charged intermediates. This step (which leads to cationic
C–N coupled products) is therefore favored by more polar solvents.
An alternative non-directed C–H activation is also possible
that does not involve acetate displacement and so becomes favored
in low polarity solvents, leading to C–C coupled products.
Alkyne insertion is generally more favorable for diphenylacetylene
over 4-octyne, but the reverse is true of the reductive coupling step.
The diphenylacetylene moiety can also stabilize unsaturated seven-membered
rhodacycle intermediates through extra interaction with one of the
Ph substituents. With 1-phenylpyrazole this effect is sufficient to
suppress the final C–N reductive coupling. A comparison of
a series of seven-membered rhodacycles indicates the barrier to coupling
is highly sensitive to the two groups involved and follows the trend
C–N+ > C–N > C–C (i.e., involving
the formation of cationic C–N, neutral C–N, and neutral
C–C coupled products, respectively).