# Electrochemical and Photoredox Catalysis for Constructing 5,5‐Spirocycles via Reductive Activation of N‐alkoxyphthalimides for the Total Synthesis of (−)‐Cephalosporolide F

## TL;DR

This paper presents a green chemical method using electrochemical and photocatalytic techniques to synthesize a complex natural product, Cephalosporolide F, avoiding toxic and expensive reagents.

## Contribution

The study introduces a sustainable synthetic strategy for constructing [5,5]-spiroketals using redox methods without toxic stannyl reagents or costly metal catalysts.

## Key findings

- Electrochemical and photoredox catalytic methods enable the stereoselective synthesis of (−)-Cephalosporolide F.
- Diphenylphosphate-derived substrates show superior performance in electrochemical transformations.
- The PRC method with an iridium catalyst yields slightly higher results than the electrochemical approach.

## Abstract

The electrosynthetic (ES) approach employing rapid alternating polarity electrolysis and blue LED photoredox catalysis (PRC) is revised and compared in the synthesis of [5,5]‐spiroketals through a tandem reductive activation of N‐alkoxyphthalimides to alkoxy radical, followed by hydrogen atom transfer, and spirocyclization sequence. The role of leaving group and redox conditions is explored in the electrochemical transformation, revealing that diphenylphosphate‐derived substrates exhibit superior performance. Both methodologies enable the stereoselective synthesis of (−)‐Cephalosporolide F from the chiral pool, with a slightly higher yield for the PRC involving an iridium catalyst. This study showcases the potential use of electrochemical and photochemical green redox methodologies for radical‐mediated transformations and late‐stage synthesis of natural products, avoiding toxic stannyl reagents and bypassing expensive metal‐based catalysts. These findings support the development of more sustainable synthetic strategies for complex natural products while acknowledging the use of CH2Cl2 and tetrabutylammonium salts in the ES procedure.

The spirocyclization of N‐alkoxyphthalimides carbohydrate derivatives through electrochemical and photocatalytic redox approaches is evaluated. The electrochemical conditions prove effective in promoting the formation of the [5,5]‐spiroketal core found in Cephalosporolide F.© 2025 WILEY‐VCH GmbH