Synthesis of Highly Substituted Oxazoles through Iodine(III)-Mediated Reactions of Ketones with Nitriles

Akio Saito,Yuji Hanzawa,Nao Hyodo

doi:10.3390/molecules170911046

Akio Saito, Yuji Hanzawa + Show 1 more

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https://doi.org/10.3390/molecules170911046

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Journal: Molecules (Basel, Switzerland)	Publication Date: Sep 13, 2012
Citations: 36	License type: CC BY 4.0

Affiliation: Showa Pharmaceutical University

Abstract

In the presence of trifluoromethanesulfonic acid (TfOH) or bis(trifluoromethane-sulfonyl)imide (Tf2NH), iodosobenzene (PhI=O) efficiently promoted the reactions of dicarbonyl compounds as well as monocarbonyl compounds with nitriles to give 2,4-disubstituted and 2,4,5-trisubstituted oxazole in a single step under the mild conditions.

Highlights

The synthesis of oxazole compounds has attracted a great deal of attention due to the widespread application of oxazole derivatives in biologically active compounds as well as versatile building blocks in organic synthesis [1,2,3]
Phenyliodine(III) diacetate (PIDA) with trifluoromethanesulfonic acid (TfOH) [22] or the iodoarene-oxone-TfOH system [23] efficiently promoted the direct synthesis of oxazoles from monocarbonyl compounds, such as alkyl aryl ketones with nitriles
The use of p-toluenesulfonic aicd (TsOH) gave -tosyloxy ketone 3 as a main product, the other acids led to the desired formation of oxazole compound 2a

Summary

Introduction

The synthesis of oxazole compounds has attracted a great deal of attention due to the widespread application of oxazole derivatives in biologically active compounds as well as versatile building blocks in organic synthesis [1,2,3]. For the purpose of synthesizing highly substituted oxazole compounds, an intramolecular reaction, the so-called Robinson-Gabriel cyclocondensation of -acylamino ketones in the presence of dehydrating reagents [H2SO4, POCl3, (CF3SO2)2O, and so on] has been commonly employed [4,5,6]. Phenyliodine(III) diacetate (PIDA) with trifluoromethanesulfonic acid (TfOH) [22] or the iodoarene-oxone-TfOH system [23] efficiently promoted the direct synthesis of oxazoles from monocarbonyl compounds, such as alkyl aryl ketones with nitriles. To the best of our knowledge, there is no report about the direct synthesis of oxazoles from simple dicarbonyl compounds and nitriles [21,24,25]. We describe a single-step synthesis of highly substituted oxazoles by the reaction of ketones with nitriles in the presence of iodosobenzene (PhI=O) and a Brønsted acid

Evaluation of Oxidants for the Direct Synthesis of Oxazole

Procedure

Mechanistic Considerations

General

Conclusions