Chemistry of Carbon-Substituted Derivatives of Cobalt Bis(dicarbollide)(1−) Ion and Recent Progress in Boron Substitution

Abstract

The cobalt bis(dicarbollide)(1−) anion (1−), [(1,2-C2B9H11)2-3,3′-Co(III)](1−), plays an increasingly important role in material science and medicine due to its high chemical stability, 3D shape, aromaticity, diamagnetic character, ability to penetrate cells, and low cytotoxicity. A key factor enabling the incorporation of this ion into larger organic molecules, biomolecules, and materials, as well as its capacity for “tuning” interactions with therapeutic targets, is the availability of synthetic routes that enable easy modifications with a wide selection of functional groups. Regarding the modification of the dicarbollide cage, syntheses leading to substitutions on boron atoms are better established. These methods primarily involve ring cleavage of the ether rings in species containing an oxonium oxygen atom connected to the B(8) site. These pathways are accessible with a broad range of nucleophiles. In contrast, the chemistry on carbon vertices has remained less elaborated over the previous decades due to a lack of reliable methods that permit direct and straightforward cage modifications. In this review, we present a survey of methods based on metalation reactions on the acidic C-H vertices, followed by reactions with electrophiles, which have gained importance in only the last decade. These methods now represent the primary trends in the modifications of cage carbon atoms. We discuss the scope of currently available approaches, along with the stereochemistry of reactions, chirality of some products, available types of functional groups, and their applications in designing unconventional drugs. This content is complemented with a report of the progress in physicochemical and biological studies on the parent cobalt bis(dicarbollide) ion and also includes an overview of recent syntheses and emerging applications of boron-substituted compounds.

Synthetic routes to carbon substituted cobalt bis(dicarbollide) alkyl halides and aromatic amines along with closely related irregular pathways

“…The molecular structures of 16 and 18 unambiguously confirmed the particular type of substitution and the zwitterionic character of both compounds. As we found later, the thermal decomposition of C(1), C(1′) disubstituted ethyl methanesulfonyl ester, rac -[(1,1′-(MsOC 2 H 4 ) 2 -1,2-C 2 B 9 H 10 ) 2 -3,3′-Co]Me 4 N ( 19 ) 6,9,37 at 90 °C for 48 h provides high yields of an isomeric mixture consisting of doubly bridged compounds [(1,7-μ-C 2 H 4 -1,2-C 2 B 9 H 9 ) 2 -3,3′-Co]Me 4 N (Me 4 N 20a ) and [(1,8-μ-C 2 H 4 -1,2-C 2 B 9 H 9 ) 2 -3,3′-Co]Me 4 N (Me 4 N 20b ) (see Scheme 5 and Fig. 5 and 6).…”

“…The influence of reaction conditions on the yields of the model aniline product was tested using propylbromide 3c − and 1-amino-4-Me-benzene ( p-toluidine) (6) and the data are summarized in Table 1. It can be seen that the most efficient conditions comprise 2.0 equivalents of KOtBu and aniline 6 in PhMe at 100 °C (entry 14).…”

“…[2][3][4][5] For these reasons, it has attracted the attention of chemists interested in innovative solutions to a variety of challenges in areas such as medicinal and physical chemistry, and it is the subject of several review articles and book chapters. [2][3][4][5][6] Thus, the COSAN(1-) ion and its derivatives have been investigated in the context of, for example, boron neutron capture therapy, 7,8 HIV protease inhibitors, 9,10 carbonic anhydrase inhibitors, 11,12 or antibacterial agents, [13][14][15][16][17][18][19] extraction agents of radionuclides from used radioactive fuel, [20][21][22][23] or photochemistry. 24,25 This wide potential feeds a demand for more versatile and variable synthetic methods to yield COSAN derivatives.…”

“…Two main sites for the substitution of COSAN ions can be distinguishedthe hydridic site at the B8 and B8′ vertices and the acidic site at the carbon vertices C1/C2 and C1′/C2′. 6 Regarding boron-site substitutions, Plešek et al disclosed in their pioneering work a dioxane ring-cleavage reaction that opened up a generic route to a series of COSAN derivatives. 26 Direct halogenation [27][28][29][30] and other substitutions at the B8 and B8′ positions have also been studied.…”

“…4 Molecular structure of 18 (CCDC 2246098, † ellipsoids drawn at the 50% probability level). Selected interatomic distances [Å] and angles [°]: Co3-C1'2.0499(16), Co3-C1 2.1067(16), Co3-C2' 2.0736(16), Co3-C2 2.0572(17), Co3-B4' 2.0914(18), Co3-B8' 2.1230(19), Co3-B4 2.0905 (19), Co3-B7' 2.1085(19), Co3-B7' 2.1085(19), Co3-B1 2.0998(19), Co3-B7 2.0854(19), C2'-Co3-B1 170.40(7), C2'-Co3-B7 135.79(7), C2-Co3-C1 46.67(6), C2-Co3-C2' 104.93(7), C2-Co3-B4' 171.75(7), C2-Co3-B8' 125.79(7), C2-Co3-B4 82.35(7), C2-Co3-B7'95.70(7), C2-Co3-B1 84.67(7), C2-Co3-B7 49.43(7), B4'-Co3-C1 135.89(7), B4'-Co3-B8' 50.91(7), B4'-Co3-B7' 86.89(7), B4'-Co3-B187.81(8), B4-Co3-C1 47.73(7), B4-Co3-B4' 95.53(8), B4-Co3-B8' 133.36(7), B4-Co3-B7' 175.99(7), B4-Co3-B1 50.88(7), B7'-Co3-B8' 50.53(7), B1-Co3-C1 84.48(7), B1-Co3-B8' 91.53(7), B1-Co3-B7'132.57(7), B7-Co3-C1 84.34(7), B7-Co3-B4' 122.64(8), B7-Co3-B8' 87.49(7), B7-Co3-B4 87.10(8), B7-Co3-B7' 94.30(7), and B7-Co3-B1 51.21(7).…”