Remote, Diastereoselective Cobalt-Catalyzed Alkene Isomerization–Hydroboration: Access to Stereodefined 1,3-Difunctionalized Indanes

Abstract

The remote, diastereoselective hydroboration of 2- and 3-substituted indenes with a 2,2′:6′,2″-terpyridine cobalt alkyl precatalyst is described that maintains high regio- and stereoselectivity independent of the starting position of the alkene. Several 1,2- and 1,3-disubstituted indanyl boronate esters were obtained with exclusive (>20:1 dr) selectivity for the trans diastereomer including synthetically versatile, stereodefined diboron derivatives. Alkene isomerization by a putative cobalt hydride intermediate precedes carbon–boron bond formation, leading to the observed regioselectivity for boron incorporation at the unsubstituted C(sp3)–H benzylic site. The regio- and diastereoselectivity of the transformation were maintained independent of the starting position of the alkene, as demonstrated by hydroboration of three isomers of methyl-substituted indene. Deuterium-labeling experiments support rapid and reversible insertion and β-hydride elimination to isomerize 3-methylindene and 1-exo-methylene-indane, accounting for the isotopic distribution observed in the products. Mechanistic studies, including stoichiometric experiments, density functional theory calculations, and kinetic analysis, support a mechanism in which 2,3-alkene insertion into a cobalt hydride intermediate determines both the regio- and diastereoselectivity of the catalytic reaction. Synthetic applications of the indanyl boronate esters were demonstrated through the elaboration of the products to several examples of 1,3-disubstituted indanes, important carbocyclic structural motifs in both pharmacological and bioactive molecules.