A Strategy for Selective Catalytic B–H Functionalization of o-Carboranes

Conspectus Carboranes are a class of polyhedral carbon–boron molecular clusters featuring three-dimensional aromaticity, which are often considered as 3D analogues of benzene. Their unique structural and electronic properties make them invaluable building blocks for applications ranging from functional materials to versatile ligands to pharmaceuticals. Thus, selective functionalization of carboranes has received tremendous research interest. In earlier days, the vast majority of the works in this area were focused on cage carbon functionalization via facile deprotonation of cage CH, followed by reaction with electrophiles. On the contrary, cage B–H activation is very challenging since the 10 B–H bonds on o -carborane are very similar, and how to achieve the desired transformation at specific boron vertex is a long-standing issue. As carbon is considered more electronegative than boron, this property results in different vertex charges on the o -carborane cage, which follow the order B(3,6)–H ≪ B(4,5,7,11)–H < B(8,10)–H < B(9,12)–H. We thought that this difference may trigger the favorite interaction of a proper transition metal complex with a specific B–H bond of carborane, which could be utilized to solve the selectivity issue. Accordingly, our strategy is described as follows: (1) electron-rich transition metal catalysts are good for the activation of the most electron-deficient B(3,6)–H bonds (connected to both cage C–H vertices); (2) electron-deficient transition metal catalysts are good for the activation of the relatively electron-rich B(8,9,10,12)–H bonds (with no bonding to either cage C–H vertices); and (3) directing-group-assisted transition metal catalysis is appropriate for the activation of the B(4,5,7,11)–H bonds (connected to only one cage C–H vertex), whose vertex charges lie in the middle of the range for the 10 B–H bonds. This strategy has been successfully applied by our laboratory and other groups in the development of a series of synthetic routes for catalytic selective activation of B–H bonds of the carborane cage, resulting in the synthesis of a large number of cage-boron-functionalized carborane derivatives in a regioselective and catalytic fashion. Subsequently, significant progress in this emerging area has been made. In 2013 we reported the selective tetrafluorination of o -carboranes at the B(8,9,10,12)–H bonds using an electron-deficient Pd(II) salt, [Pd(MeCN) 4 ][BF 4 ], as the catalyst. In 2014 we disclosed the first example of carboxy-directed alkenylation of o -carboranes at the B(4) vertex promoted by an Ir(III) catalyst. Subsequently, in 2017 we presented an electron-rich Ir(I)-catalyzed diborylation of o -carboranes at the B(3,6)–H bonds. We also uncovered the first example of Pd-catalyzed asymmetric synthesis of chiral-at-cage o -carboranes in 2018. These proof-of-principle studies have greatly stimulated research activities in selective B–H activation of carboranes and boron clusters enabled by transition metal catalysts. We have so far developed a toolbox of synthetic methods for selective catalytic cage B-olefination, -arylation, -alkenylation, -alkynylation, -oxygenation, -sulfenylation, -borylation, -halogenation, and -amination. We have recently expanded our research to base metal catalysis. As the field progresses, we expect that other methods for regioselective cage B–H activation will be invented, and the results detailed in this Account will promote these efforts.