Photocatalytic Reductive Radical-Polar Crossover for a Base-Free Corey-Seebach Reaction.

Karsten Donabauer,Urša Rozman,Kathiravan Murugesan,Stefano Crespi,Burkhard König

doi:10.1002/chem.202003000

Karsten Donabauer, Urša Rozman + Show 3 more

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https://doi.org/10.1002/chem.202003000

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Journal: Chemistry	Publication Date: Sep 17, 2020
Citations: 30	License type: CC BY 4.0

Affiliation: University of Regensburg, University of Groningen

Abstract

A metal‐free generation of carbanion nucleophiles is of prime importance in organic synthesis. Herein we report a photocatalytic approach to the Corey–Seebach reaction. The presented method operates under mild redox‐neutral and base‐free conditions giving the desired product with high functional group tolerance. The reaction is enabled by the combination of photo‐ and hydrogen atom transfer (HAT) catalysis. This catalytic merger allows a C−H to carbanion activation by the abstraction of a hydrogen atom followed by radical reduction. The generated nucleophilic intermediate is then capable of adding to carbonyl electrophiles. The obtained dithiane can be easily converted to the valuable α‐hydroxy carbonyl in a subsequent step. The proposed reaction mechanism is supported by emission quenching, radical–radical homocoupling and deuterium labeling studies as well as by calculated redox‐potentials and bond strengths.

Highlights

A metal-free generation of carbanion nucleophiles is of prime importance in organic synthesis
A classical method to synthesize this class of compound is the well-known Corey–Seebach umpolung first reported in 1965.[2]. In their seminal and subsequent work, they describe the deprotonation of dithianes by a strong base, yielding an acyl anion equivalent
We reported that radicals generated by the combination of photo- and hydrogen atom transfer (HAT)-catalysis can be reduced to render an anionic intermediate capable of reacting with electrophiles.[16]

Summary

Introduction

A metal-free generation of carbanion nucleophiles is of prime importance in organic synthesis. A double bond within the electrophile (2 g) gave the desired product despite a potential radical addition as side reaction and ketones bearing a phenyl ring with various substituents (2 h–k) were all tolerated. With a substrate containing both, an electrophilic ketone and ester group (2 q) the nucleophilic addition proceeded exclusively at the more reactive ketone moiety, yielding the corresponding lactone product (3 aq) resulting from an attack of the formed alcohol to the ester.

Results

Conclusion