# Photoinduced, Chemoselective γ‐Alkylation of 2‐Silyloxyfurans With α‐Bromoketones: A Rapid Entry to Chiral ε‐Keto‐γ‐Butenolides

## TL;DR

This paper introduces a new one-step method to create chiral ε-ketobutenolides using light, which can be used to build complex molecules.

## Contribution

A novel photoinduced γ-alkylation method for synthesizing ε-ketobutenolides in high yields.

## Key findings

- The γ-alkylation of 2-silyloxyfurans with α-bromoketones was achieved using blue light.
- The method provides access to chiral ε-ketobutenolides in one step and high yields.
- The scaffolds were used to create new heterobicyclic derivatives like phenyltetrahydrofurofuran and tetrahydrofuro-pyridazinone.

## Abstract

γ‐Butenolides are widespread structural motifs found in many natural and unnatural products which display an impressive range of biological activities. Among them, ε‐keto‐γ‐butenolides represent underestimated butenolide frameworks, which could serve as valuable platforms to build complex structures, for example, heterobicyclic derivatives. Quite unexpectedly, despite the apparent simplicity of their structures, efficient synthetic methodologies enabling the construction of chiral, ε‐keto‐γ‐butenolide architectures are quite underdeveloped. In this context, herein we present a novel, photoinduced regio‐ and chemoselective γ‐alkylation of 2‐silyloxyfurans with 2‐bromoketones providing a practical access to ε‐ketobutenolide scaffolds in racemic format, in one single step and high yields. The usefulness of these products as starting materials to build chiral, fused‐heterobicycle lactone derivatives was demonstrated by the implementation of a two‐step strategy which successfully delivered unprecedented phenyltetrahydrofuro[3,2‐b]furan‐2(3H)‐one and tetrahydrofuro[3,2‐c]pyridazin‐6(1H)‐one chemotypes.

A photoinduced, regio‐ and chemoselective γ‐alkylation of 2‐silyloxyfurans with a‐bromoketones was achieved by exploiting a photoredox catalytic process promoted by blue light. This approach provides practical and efficient access to chiral, ε‐ketobutenolides, in one step and high yields. The usefulness of these scaffolds as versatile platforms to access complex, heterobicyclic molecules via late‐stage modifications was also demonstrated.