# Direct synthesis of bicyclo[1.1.1]pentane (BCP) boronates from carboxylic acids

## TL;DR

This paper introduces a new single-step method to convert carboxylic acids into BCP boronic esters, which are important for drug development.

## Contribution

A general, single-step method for directly converting carboxylic acids into BCP boronic esters using a synergistic HAT/LMCT process.

## Key findings

- BCP boronates are obtained in good yields using irradiation and an iron catalyst.
- The method shows broad substrate scope and functional group tolerance.
- BCP analogs of approved drugs were synthesized, demonstrating practical utility.

## 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.

Bicyclo[1.1.1]pentane (BCP) boronic esters are crucial synthetic intermediates for the synthesis of a variety of BCP-containing drugs with improved pharmacokinetic properties. Here, the authors report a general approach to BCP boronic ester via direct, single-step decarboxylation of carboxylic acids.