Step-by-Step Multifunctionalization of Isoxazoles Based On S_EAr Reactions and C–H Direct Arylations

Abstract

Functionalized isoxazoles are important as pharmaceuticals and agrochemicals. Generally, electrophilic aromatic substitution or generation of carbanions/electrophilic trapping approach is used to introduce functional groups into unsubstituted heteroaromatics. However, these approaches have not been simple to apply to unsubstituted isoxazoles due to their poor nucleophilicity and instability under basic conditions. Recently several approaches have been reported to overcome these problems. This review summarizes the functionalization of isoxazoles, including S_EAr reactions and C–H direct arylations, towards the step-by-step multifunctionalization of isoxazoles.

1 Introduction

2 S_EAr Reaction of Isoxazoles

3 Preparation of Isoxazolyl Anions and Their Use for the Synthesis of Functionalized Isoxazoles

4 Other C–C and C–N Bond Formations of Isoxazoles

5 Transition-Metal-Catalyzed C–H Direct Functionalization of Isoxazoles

6 Step-by-Step Multifunctionalization of Isoxazoles

7 Summary and Outlook

Key words

isoxazole - S_EAr - isoxazolyl anion - C–H direct functionalization - cross-coupling

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Selected reports for clinically used isoxazole containing pharmaceuticals, parecoxib, leflunomide, isocarboxazid, and oxacillin, see:
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