Enantioselective Synthesis of C–B Axial Chirality via Isothiourea-Catalyzed Acylative Kinetic Resolution

Abstract

C–B axially chiral compounds constitute a significant class of stereogenic molecules with growing importance in advanced materials science and pharmaceutical chemistry, particularly as chiral ligands, functional building blocks, and bioactive scaffolds. However, the catalytic asymmetric construction of such stereogenic axes remains a formidable synthetic challenge, primarily due to the elongated C(sp²)-B bond length and its correspondingly low rotational energy barrier, which often leads to configurational instability. To date, asymmetric catalytic synthesis of C – B axially chiral compounds has predominantly employed metal catalysis, whereas organic catalytic strategies remain scarce. In this work, we disclose a highly efficient organocatalytic kinetic resolution (KR) strategy for the selective synthesis of enantioenriched C–B axially chiral compounds. Our method employs a readily accessible tetraimidazole catalyst and utilizes isobutyric anhydride as reactive substrates. This protocol affords the desired axially chiral boranes in high yields and excellent enantioselectivities (with selectivity factor up to 121). The practical utility of this methodology was demonstrated through successful gram-scale synthesis and a series of downstream functional group transformations, highlighting its potential for synthetic applications. The racemization experiments established that the rotational barriers of the axially chiral compound was 41.7 kcal/mol, a value that confirms sufficient thermodynamic stability for the isolation, characterization, and further application of these compounds at ambient conditions. Mechanistic investigations, including a set of control experiments, revealed a critical dual role of the iodine atom present in the reaction: it not only provides steric bulk to impede the rotation around the C–B bond but also plays an important role in governing the stereochemical outcome of the reaction. In addition, the origin of enantioselectivity was elucidated through density functional theory (DFT) calculations.

Keywords

Atropisomers / C–B axis / Asymmetric catalysis / Kinetic resolution / Isothiourea catalysis / Anhydride / Organic boron / 1,2-Azaborine

RIGHTS & PERMISSIONS

2026 SIOC, CAS, Shanghai, & WILEY-VCH GmbH