Enantioselective Synthesis of Chiral-at-Cage o-Carboranes via Pd-Catalyzed Asymmetric B–H Substitution

Abstract

Carborane cage chirality is an outstanding issue of great interest as the icosahedral carboranes have wide applications in medicinal and materials chemistry. The synthesis of optically active carborane derivatives, whose chirality is associated with the substitution patterns on the polyhedron, will open new avenues to carborane chemistry. We report herein an efficient method to achieve chiral-at-cage arylation of o-carboranes with high regio- and enantioselectivities by a strategy of palladium-catalyzed asymmetric intramolecular B-H arylation and cyclization. This represents the first example of the enantioselective reaction on carboranes, providing an efficient way for the construction of chiral-at-cage compounds with new skeletons.

Borinostats: solid-phase synthesis of carborane-capped histone deacetylase inhibitors with a tailor-made selectivity profile

“…32,33 As opposed to carbon cage structures, for carboranes manifold achiral, chiral and chiral-at-cage modifications at carbon-as well as at boron-vertices are described in the literature, thus paving the way also for the evaluation and design of target-specific asymmetric drugs. 34,35 While boron-containing drugs like bortezomib, crisaborole and tavaborole are established therapeutics, carborane drugs are still scarce in clinical trials. 30,36,37,38 Within this branch, a limited number of boron-containing HDACis have been investigated.…”

“… 32,33 As opposed to carbon cage structures, for carboranes manifold achiral, chiral and chiral-at-cage modifications at carbon- as well as at boron-vertices are described in the literature, thus paving the way also for the evaluation and design of target-specific asymmetric drugs. 34,35 …”

Natural-Product-Directed Catalytic Stereoselective Synthesis of Functionalized Fused Borane Cluster–Oxazoles for the Discovery of Bactericidal Agents

“…However, there are limited reports on the enantioselective synthesis of such chiral compounds, and their utility has not been explored. 28 − 31 …”

Ir-catalyzed enantioselective B−H alkenylation for asymmetric synthesis of chiral-at-cage o‑carboranes

“…Inspired by the recent reports on fullerene cage chirality 36 – 39 and ferrocene planar chirality 40 , the transition-metal-catalyzed enantioselective B–H functionalization should realize the synthesis of optically pure chiral-at-cage o -carborane derivatives, which are important in the fields of asymmetric synthesis, materials science, and medicinal chemistry, where the chirality plays an important role in molecular design. We have very recently reported a proof-of-concept study on enantioselective synthesis of chiral-at-cage o -carborane derivatives via a Pd-catalyzed intramolecular B(5)–H arylation of o -carboranes in the presence of chiral phosphine ligands 41 .

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