Accessing Perfluoroaryl Sulfonimidamides and Sulfoximines via Photogenerated Perfluoroaryl Nitrenes: Synthesis and Application as a Chiral Auxiliary.

Julius Kuzmin,Peter Dinér,Azamat Z Temerdashev,Giampiero Proietti

doi:10.1021/acs.joc.1c02241

Julius Kuzmin, Peter Dinér + Show 2 more

Open Access

https://doi.org/10.1021/acs.joc.1c02241

Copy DOI

Abstract

Sulfonimidamides (SIAs) and sulfoximines (SOIs) have attracted attention due to their potential in agriculture and in medicinal chemistry as bioisosteres of biologically active compounds, and new synthetic methods are needed to access and explore these compounds. Herein, we present a light-promoted generation of perfluorinated aromatic nitrenes, from perfluorinated azides, that subsequently are allowed to react with sulfinamides and sulfoxides, generating achiral and chiral SIAs and SOIs. One of the enantiopure SIAs was evaluated as a novel chiral auxiliary in Grignard additions to the imines yielding the product in up to 96:4 diastereomeric ratio.

Highlights

During the last decades, the utility of sulfonimidamides (SIAs)[1−5] and sulfoximines (SOIs)[6−12] has been demonstrated in synthesis, agrochemical applications, and as bioisosteres in medicinal chemistry due to their notable properties, such as basicity, nucleophilicity, and solubility in polar solvents
We investigated a light-promoted approach to ortho-fluoro nitrenes from perfluorinated aromatic azides (PFAAs), leading to the stereospecific addition to SAs and SOs
Upon the irradiation of PFAA (1a) in dimethyl sulfoxide (DMSO) with a 390 nm light-emitting diode (LED) light, we noticed the formation of an SOI adduct between the in situ generated perfluoroaryl nitrene and DMSO

Summary

Introduction

The utility of sulfonimidamides (SIAs)[1−5] and sulfoximines (SOIs)[6−12] has been demonstrated in synthesis, agrochemical applications, and as bioisosteres in medicinal chemistry due to their notable properties, such as basicity, nucleophilicity, and solubility in polar solvents. The classical synthetic routes[13] to access SIAs usually rely on the formation of sulfonimidoyl chloride as a precursor, followed by an amidation reaction (Figure 1). Sulfonimidoyl chloride can be generated in several different ways, such as oxidative imidation (Figure 1a),[14] oxidative chlorination (Figure 1b),[15] deoxychlorination[16] (Figure 1c), and via Grignard addition to a sulfinylamine, followed by chlorination (Figure 1d).[17] sulfur−fluorine exchange reactions (Figure 1e) with sulfonimidoyl fluoride as the key intermediate have been used to yield SIAs.[18,19] Other approaches to form SIAs involve copper-catalyzed transamidation of sulfinamides (SAs) or copper-catalyzed oxidation of methyl SOIs.[20,21] several metal-free approaches using N−H transfer to SAs have been disclosed.[22]

Methods

Results

Conclusion