Faculty, Staff and Student Publications

Language

English

Publication Date

2-23-2026

Journal

Nature Communications

DOI

10.1038/s41467-026-69851-w

PMID

41730890

PMCID

PMC13039371

PubMedCentral® Posted Date

2-23-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Bicyclo[1.1.1]pentane (BCP) boronic esters are crucial intermediates for accessing BCP-containing drugs with improved pharmacokinetic profiles, yet their synthesis typically relies on pre-formed redox-active esters derived from carboxylic acids. Here we report a general, single-step method for the direct conversion of carboxylic acids into BCP boronic esters. Upon irradiation of carboxylic acids with [1.1.1]propellane and bis(pinacolato)diboron (B2pin2) in dimethyl sulfoxide (DMSO), BCP boronates are obtained in good yields, which are further enhanced by the addition of an iron catalyst. Mechanistic studies suggest that photolytic cleavage of a B2pin2–DMSO complex initiates decarboxylation via hydrogen atom transfer (HAT), while iron catalysis enables a parallel ligand-to-metal charge transfer (LMCT) pathway. This synergistic HAT/LMCT process displays broad substrate scope and remarkable functional group tolerance. Additionally, BCP analogs of two approved drugs, butenafine and buclizine, have been readily synthesized, underscoring the potential of this dual HAT/LMCT paradigm to reshape strategies in synthetic chemistry and drug discovery.

Keywords

Synthetic chemistry methodology, Photocatalysis

Published Open-Access

yes

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