# Triplet Energy Transfer-Mediated Intermolecular Paternò–Büchi Reaction for the Synthesis of Trifluoromethylated Oxetanes

## TL;DR

This paper introduces a new light-based method to create trifluoromethylated oxetanes, which are useful in drug development.

## Contribution

A novel visible-light-mediated Paternò–Büchi reaction for synthesizing trifluoromethylated oxetanes with high selectivity.

## Key findings

- The method produces a broad range of CF3-containing oxetanes with excellent regio- and diastereoselectivity.
- Mechanistic studies show the [2 + 2] cycloaddition proceeds preferentially from the triplet excited state of the CF3-substituted carbonyl partner.

## Abstract

Oxetanes are increasingly used as compact, polar carbonyl
(bio)­isosteres
in drug discovery, and the combination with a trifluoromethyl group
enables fine-tuning of molecular properties. Here, we report a visible-light-mediated
Paternò–Büchi strategy that accesses CF3-containing oxetanes via triplet-energy-transfer activation and delivers
a broad range of CF3-containing oxetane products with excellent
regio- and diastereoselectivity. Mechanistic studies indicate that
although sensitization of both the alkene and carbonyl occurs in solution,
the subsequent stepwise [2 + 2] cycloaddition proceeds preferentially
from the triplet excited state of the CF3-substituted carbonyl
partner.