Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation-cyclization cascade mediated by K2S2O8.

Qiang Liu,Weibang Lu,Guanqun Xie,Xiaoxia Wang

doi:10.3762/bjoc.16.164

Qiang Liu, Weibang Lu + Show 2 more

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https://doi.org/10.3762/bjoc.16.164

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Abstract

A variety of chroman-4-ones bearing phosphine oxide motifs were conveniently synthesized from readily available diphenylphosphine oxides and alkenyl aldehydes via a metal-free tandem phosphinoylation/cyclization protocol. The reaction utilizes K2S2O8 as oxidant and proceeds in DMSO/H2O at environmentally benign conditions with a broad substrate scope and afforded the title compounds in moderate yields.

Highlights

The chroman-4-one framework is a privileged structural motif found in numerous natural products and pharmaceuticals with extraordinary biological and pharmaceutical activities such as anticancer activities and anti-HIV activity among others (Figure 1) [1,2,3]
Motivated by the desire to develop a metal-free and environmentally benign protocol for the construction of phosphine oxide-functionalized chroman-4-ones, we focused on the cascade cyclization employing 2-(allyloxy)benzaldehyde (1a) and diphenylphosphine oxide (DPPO, 2a) as the model substrates with K2S2O8 as the oxidant, which is a cheap, readily available, and versatile oxidant
On the basis of literature reports [29,30] and our continuing interest in green chemistry [31,32], we set the temperature at 70 °C based on the fact that K2S2O8 thermally decomposes forming sulfate radicals (SO4·−) [29,30], which may react with the substrates to furnish such a cascade cyclization

Summary

Introduction

The chroman-4-one framework is a privileged structural motif found in numerous natural products and pharmaceuticals with extraordinary biological and pharmaceutical activities such as anticancer activities and anti-HIV activity among others (Figure 1) [1,2,3]. In 2016 Li’s group [28] reported a silver-catalyzed straightforward approach for the synthesis of phosphonate-functionalized chroman-4-ones via a phosphoryl radical-initiated cascade cyclization of 2-(allyloxy)arylaldehydes using K2S2O8 as an oxidant, diphenylphosphine oxide (DPPO) was not suitable for the transformation (Scheme 1b). We present a transition-metal-free radical cascade cyclization to access the desired chroman-4-one derivatives in one pot under environmentally benign conditions (Scheme 1c).

Results

Conclusion