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

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.