The mechanism of the zirconium-catalyzed condensation of carboxylic acids and amines for direct formation of amides was studied using kinetics, NMR spectroscopy, and DFT calculations. The reaction is found to be first order with respect to the catalyst and has a positive rate dependence on amine concentration. A negative rate dependence on carboxylic acid concentration is observed along with S-shaped kinetic profiles under certain conditions, which is consistent with the formation of reversible off-cycle species. Kinetic experiments using reaction progress kinetic analysis protocols demonstrate that inhibition of the catalyst by the amide product can be avoided using a high amine concentration. These insights led to the design of a reaction protocol with improved yields and a decrease in catalyst loading. NMR spectroscopy provides important details of the nature of the zirconium catalyst and serves as the starting point for a theoretical study of the catalytic cycle using DFT calculations. These studies indicate that a dinuclear zirconium species can catalyze the reaction with feasible energy barriers. The amine is proposed to perform a nucleophilic attack at a terminal η-carboxylate ligand of the zirconium catalyst, followed by a C-O bond cleavage step, with an intermediate proton transfer from nitrogen to oxygen facilitated by an additional equivalent of amine. In addition, the DFT calculations reproduce experimentally observed effects on reaction rate, induced by electronically different substituents on the carboxylic acid.

Like the importance of benzyne, witnessed in modern arene chemistry for decades, 1,2-dehydro-o-carborane (o-carboryne), a three-dimensional relative of benzyne, has been used as a synthon for generating a wide range of cage, carbon-functionalized carboranes over the past 20 years. However, the selective B functionalization of the cage still represents a challenging task. Disclosed herein is the first example of 1,3-dehydro-o-carborane featuring a cage C-B bond having multiple bonding characters, and is successfully generated by treatment of 3-diazonium-o-carborane tetrafluoroborate with non-nucleophilic bases. This presents a new methodology for simultaneous functionalization of both cage carbon and boron vertices.

The diborene 1 was synthesized by reduction of a mixture of 1,2-di-9-anthryl-1,2-dibromodiborane(4) (6) and trimethylphosphine with potassium graphite. The X-ray structure of 1 shows the two anthryl rings to be parallel and their π(C ) systems perpendicular to the diborene π(B=B) system. This twisted conformation allows for intercalation of the relatively high-lying π(B=B) orbital and the low-lying π* orbital of the anthryl moiety with no significant conjugation, resulting in a small HOMO-LUMO gap (HLG) and ultimately a C-H borylation of the anthryl unit. The HLG of 1 was estimated to be 1.57 eV from the onset of the long wavelength band in its UV/Vis absorption spectrum (THF, λ =788 nm). The oxidation of 1 with elemental selenium afforded diboraselenirane 8 in quantitative yield. By oxidative abstraction of one phosphine ligand by another equivalent of elemental selenium, the B-B and C -H bonds of 8 were cleaved to give the cyclic 1,9-diborylanthracene 9.

o-Carboryne (1,2-dehydro-o-carborane) is a very useful synthon for the synthesis of a variety of carborane-functionalized heterocycles. Reaction of o-carboryne with N-protected indoles gave carborane-fused indolines if the protecting group was TMS via dearomative [2 + 2] cycloaddition or carboranyl indoles for N-alkyl ones through formal C-H insertion reaction. For N-aryl indoles, both reactions were observed, giving two products, in which the product ratio was dependent upon the nature of the substituents on the aryl rings. In general, electron-withdrawing substituents favor [2 + 2] cycloaddition, whereas electron-donating substituents promote a formal C-H insertion pathway. This reaction is also compatible with other heteroaromatics. Thus, a stepwise reaction mechanism was proposed to account for the experimental observations. These protocols offer general and efficient methods for the preparation of carborane-functionalized indoles and indolines as well as other heterocycles. The observed dearomative [2 + 2] cycloaddition represents the first example of indoles to undergo such reaction in the absence of transition metals or without UV irradiation. All new compounds were fully characterized by (1)H, (13)C, and (11)B NMR spectroscopy as well as HRMS spectrometry. Some were further confirmed by single-crystal X-ray analyses.