Palladium‐Catalyzed Enantioselective B(4)−H Chlorination of <i>o</i> ‐Carboranes by Chiral Transient Directing Groups

Comprehensive Summary The inherent chirality of three‐dimensional o ‐carborane derivatives arises from the substitution patterns on the icosahedral cage. This topic has received significantly less attention than the planar, axial, central, and helical chirality commonly observed in organic synthesis. Herein, we report an enantioselective B(4)–H chlorination of o ‐carboranes via a palladium‐catalyzed chiral transient directing group strategy. Reversible in situ formation of an imine directing group from 1‐(2‐formylaryl)‐ o ‐carboranes and α‐amino acids enables regio‐ and enantio‐selective activation of cage B–H bond. A variety of chiral‐at‐cage chlorinated products are obtained in moderate to good yields with enantioselectivities up to 99% ee. Mechanistic experiments together with density functional theory calculations support a trifluoroacetate‐assisted concerted metalation‐deprotonation pathway and reveal the key role of noncovalent interactions in controlling enantioselectivity.