Visible-Light-Mediated Strain-Release Radical Spirocyclizations: Access to Functionalized Spirocyclobutanes

Abstract

Spirocyclobutanes have gained significant attention in medicinal chemistry discovery programs due to their broad spectrum of biological activities and clinical applications. Utilizing ring strain in small molecules to drive organic transformations is one of the most powerful tools in chemical synthesis. Our research group has focused on developing new synthetic strategies enabled by ring strain to construct complex molecules selectively and efficiently. This account summarizes our recent efforts toward the synthesis of a library of functionalized spirocyclobutanes by harnessing the ring strain of bicyclo[1.1.0]butanes. Three spicrocyclization cascades have been developed to incorporate a diverse range of radical precursors into spirocycobutanes.

1 Introduction

2 Synthesis of Spirocyclobutyl Lactones and -Lactams using Bifunctional Reagents

3 Dual Photoredox/Nickel Catalysis for the Synthesis of Spirocyclobutyl Lactams

4 Synthesis of Spirocyclobutyl Oxindoles under Photoredox Catalysis

5 DFT Studies

6 Conclusion

Key words

bicyclo[1.1.0]butane - strain-release - photoredox catalysis - radicals - spirocyclobutanes - dual catalysis - bifunctional reagents

Publication History

Received: 23 September 2024

Accepted after revision: 15 October 2024

Accepted Manuscript online:
15 October 2024

Article published online:
05 November 2024

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