Palladium-Catalyzed Regio- and Monoselective B(2)–H Alkylation of Zwitterionic <i>nido</i>-Carboranes at Room Temperature in Water

The achievement of regio- and monoselective control is a fundamental challenge for the development of efficient B-H functionalization of polyhedral carboranes bearing multiple chemically similar B-H bonds. While <i>exo</i>-polyhedral B-H activation of zwitterionic <i>nido</i>-carboranes has witnessed remarkable progress, developing direct functionalization methods for the closed polyhedral B-H bonds remains a significant challenge. Herein, we report the development of a regioselective B(2)-H monoalkylation of <i>nido</i>-carboranes enabled by a novel pyridyl directing group containing a NH group that can form a favorable macrocyclic intramolecular H-bonding interaction with the alkyl substituent. A simple methyl substitution significantly enhances directing group efficacy, leading to unconventional B(2) selectivity. Exclusive monoselectivity was observed in the presence of three proximal B-H bonds, including a highly reactive <i>exo</i>-polyhedral B(11)-H site. Notably, the reaction proceeds in both water and organic solvents at room temperature.