A bis(imino)pyridine cobalt-catalyzed hydroboration of terminal alkynes with HBPin (Pin = pinacolate) with high yield and (Z)-selectivity for synthetically valuable vinylboronate esters is described. Deuterium labeling studies, stoichiometric experiments, and isolation of catalytically relevant intermediates support a mechanism involving selective insertion of an alkynylboronate ester into a Co-H bond, a pathway distinct from known precious metal catalysts where metal vinylidene intermediates have been proposed to account for the observed (Z) selectivity. The identity of the imine substituents dictates the relative rates of activation of the cobalt precatalyst with HBPin or the terminal alkyne and, as a consequence, is responsible for the stereochemical outcome of the catalytic reaction.
α,β-Unsaturated O-pivaloyl oximes are coupled to alkenes by Rh(III) catalysis to afford substituted pyridines. The reaction with activated alkenes is exceptionally regioselective and high yielding. Mechanistic studies suggest that heterocycle formation proceeds via reversible C-H activation, alkene insertion and a C-N bond formation/N-O bond cleavage process.
α,β-Unsaturated oxime pivalates are proposed to undergo reversible C(sp2)-H insertion with cationic Rh(III) complexes to furnish five-membered metallacycles. In the presence of 1,1-disubstituted olefins, these species participate in irreversible migratory insertion to give, after reductive elimination, 2,3-dihydropyridine products in good yields. Catalytic hydrogenation was then used to convert these molecules into piperidines, which are important structural components of numerous pharmaceuticals.
α,β-Unsaturated carboxylic
acids undergo Rh(III)-catalyzed decarboxylative coupling with α,β-unsaturated O-pivaloyl oximes to provide substituted pyridines in good
yield. The carboxylic acid, which is removed by decarboxylation, serves
as a traceless activating group, giving 5-substituted pyridines with
very high levels of regioselectivity. Mechanistic studies rule out
a picolinic acid intermediate, and an isolable rhodium complex sheds
further light on the reaction mechanism.
Among the fundamental
transformations that comprise a catalytic
cycle for cross coupling, transmetalation from the nucleophile to
the metal catalyst is perhaps the least understood. Optimizing this
elementary step has enabled the first example of a cobalt-catalyzed
Suzuki–Miyaura cross coupling between aryl triflate electrophiles
and heteroaryl boron nucleophiles. Key to this discovery was the preparation
and characterization of a new class of tetrahedral, high-spin bis(phosphino)pyridine
cobalt(I) alkoxide and aryloxide complexes, (iPrPNP)CoOR,
and optimizing their reactivity with 2-benzofuranylBPin (Pin = pinacolate).
Cobalt compounds with small alkoxide substituents such as R = methyl
and ethyl underwent swift transmetalation at 23 °C but also proved
kinetically unstable toward β–H elimination. Secondary
alkoxides such as R = iPr or CH(Ph)Me balanced stability
and reactivity. Isolation and structural characterization of the product
following transmetalation, (iPrPNP)Co(2-benzofuranyl),
established a planar, diamagnetic cobalt(I) complex, demonstrating
the high- and low-spin states of cobalt(I) rapidly interconvert during
this reaction. The insights from the studies in this elementary step
guided selection of appropriate reaction conditions to enable the
first examples of cobalt-catalyzed C–C bond formation between
neutral boron nucleophiles and aryl triflate electrophiles, and a
model for the successful transmetalation reactivity is proposed.
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