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

Abstract

The asymmetric synthesis of chiral-at-cage o-carboranes, whose chirality is associated with the substitution patterns on the polyhedron, is of great interest as the icosahedral carboranes have wide applications in medicinal and materials chemistry. Herein we report an intermolecular Ir-catalyzed enantioselective B−H alkenylation for efficient and facile synthesis of chiral-at-cage o-carboranes with new skeletons under mild reaction conditions. Generally very good to excellent yields with up to 99% ee can be achieved in this Ir-catalyzed B−H alkenylation. The enantiocontrol model is proposed based on Density Functional Theory calculations in which the use of chiral phosphoramidite ligand is essential for such asymmetric o-carborane B−H alkenylation.

Functionalization of o-carboranes via carboryne intermediates

“…It has been documented that the highly symmetrical 3D structure of ocarborane can be transformed to chiral-at-cage molecules with the addition of substituents to lower the symmetry of its icosahedral structure. 95,96 For example, the presence of a substituent at position B(3/6) of C(1)-substituted o-carborane results in the chirality of the molecule. 97 The development of a (C,B)-carboryne with inherent chirality is of great interest as well as challenge.…”

Regioselectivity of Pd-catalyzedo-carborane arylation: a theoretical view

“…[31][32][33] The most challenging factor in broadening the applications of carboranes is the ability to perform selective functionalizations at the desired B-H or C-H vertex. 19,[34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] In order to give a glance of icosahedral carboranes, the number system of dicarba-closo-dodecarboranes (C 2 B 10 H 12 ) has been shown in Scheme 1(a). The electrostatic potential (ESP) surface calculation of o-carborane reveals charge separation character (Scheme 1(b)), wherein the positive charge resides mainly on B-H bonds and the negative charge resides mainly on C-H bonds.…”

“…[49][50][51][52][53][54][55][56] Usually, introducing a directing group (DG) on o-carborane is a powerful way to manipulate the regioselectivities of these B-H bonds. 27,47,[57][58][59][60][61] In 2014, Xie reported a catalytic B(4)-H alkylation of carboxylic o-carboranes using Cp*IrCl 2 as catalyst. 62 Later, Yan and Lu developed a B(3)-H acetoxylation of pyridyl-modified o-carborane using Cp*RhCl 2 (Scheme 1(b)).…”

Iridium-Catalyzed Selective B(4)–H Amination of o-Carboranes with Anthranils

“…Carboranes as a class of carbon–boron molecular clusters are finding many applications as boron neutron capture therapy agents in medicines, versatile ligands in coordination/organometallic chemistry, and building blocks in materials . Consequently, the selective functionalization of carboranes has drawn more interest, and recently, a remarkable development in controlled derivatization of o -carboranes has been realized. , Accordingly, a large set of protocols have been established for the synthesis of a wide range of cage B-substituted o -carboranes, including transition-metal-catalyzed controlled cage BH functionalization using various coupling partners. − In view of the valuable applications of carboranes bearing organic nitrogen groups in pharmacophores, catalysis, , and coordination chemistry, we are particularly interested in developing a new methodology for BH amination. The established typical BH amination methods include (1) B4 amination of o -carboranes with O -benzoylhydroxylamines via Pd catalysis, (2) Ru or Ir catalyst-assisted B4 amination of o -carboranes using sulfonyl azides as aminating reagents, , (3) Rh catalyst-assisted B4–H amidation using dioxazolones, (4) Rh or Ir catalyst-assisted amination of o -carboranes employing sulfonamides or anilines (Scheme a), (5) Ir catalyst-assisted B3 amination of o -carboranes using ammonia, (6) Pd catalyst-assisted B9 amination of o -carboranes employing N sources, and (7) very recently disclosed direct nucleophilic cage BH amination using Mg­(NR 2 ) 2 (Scheme b)…”