Discovering the Site-Selective Umpolung of Ketones Triggered by Hypervalent Fluoro-Iodanes – Why Investigating Side Reactions Matters!

Abstract

In this account, we describe our journey leading to the discovery of a generally applicable umpolung method for the α-functionalization of ketones. Central to this reaction is the cyclic hypervalent fluoro-iodane, which is mostly known for various alkene functionalizations enabling, for example, the synthesis of fluoro-benzoxazepines, indoles, and ketones. During this work, we encountered α-functionalized ketones as minor side products. This observation prompted us to further investigate this reactivity, thus revealing a directed umpolung of pyridyl ketones by the fluoro-iodane. The key to the success was the unexpected non-covalent interaction between the nucleophile, substrate, and iodane.

1 Introduction

2 Cyclizations Triggered by the Fluorination of Styrenes

3 Umpolung Reactions Facilitated by Hypervalent Iodanes

4 Discovering and Evolving a Fluoro-Iodane-Triggered Regioselective α-Functionalization of Carbonyl Compounds

5 First Investigations on the Nitrogen-Directed Umpolung

6 Conclusion

Key words

hypervalent iodane - fluorination - umpolung of ketones - non-covalent interactions - α-functionalization - halogen bonding

Publication History

Received: 14 November 2022

Accepted after revision: 30 November 2022

Accepted Manuscript online:
30 November 2022

Article published online:
02 January 2023

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