C−H Activation and Cross‐Coupling of Acyclic Aldonitrone

The concerted metalation-deprotonation mechanism predicts relative reactivity and regioselectivity for a diverse set of arenes spanning the entire spectrum of known palladium-catalyzed direct arylation coupling partners. An analysis following an active strain model provides a more complete portrayal of the important arene/catalyst parameters leading to a successful coupling. The breadth of arenes whose reactivity can be predicted by the CMD mechanism indicates that it may be far more widespread than previously imagined.

Two catalytic protocols of the oxidative C-C bond formation have been developed on the basis of the C-H bond activation of pyridine N-oxides. Pd-catalyzed alkenylation of the N-oxides proceeds with excellent regio-, stereo-, and chemoselectivity, and the corresponding ortho-alkenylated N-oxide derivatives are obtained in good to excellent yields. Direct cross-coupling reaction of pyridine N-oxides with unactivated arene was also developed in the presence of Pd catalyst and Ag oxidant, which affords ortho-arylated pyridine N-oxide products with high site-selectivity.

An efficient Rh(III)- and Ir(III)-catalyzed, chelation-assisted C-H alkynylation of a broad scope of (hetero)arenes has been developed using hypervalent iodine-alkyne reagents. Heterocycles, N-methoxy imines, azomethine imines, secondary carboxamides, azo compounds, N-nitrosoamines, and nitrones are viable directing groups to entail ortho C-H alkynylation. The reaction proceeded under mild conditions and with controllable mono- and dialkynylation selectivity when both mono- and dialkynylation was observed. Rh(III) and Ir(III) catalysts exhibited complementary substrate scope in this reaction. The synthetic applications of the coupled products have been demonstrated in subsequent derivatization reactions. Some mechanistic studies have been conducted, and two Rh(III) complexes have been established as key reaction intermediates. The current C-H alkynylation system complements those previously reported under gold or palladium catalysis using hypervalent iodine reagents.