Synthesis 2017; 49(11): 2351-2360
DOI: 10.1055/s-0036-1588784
short review
© Georg Thieme Verlag Stuttgart · New York

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

Shinichiro Fuse*, Taiki Morita, Hiroyuki Nakamura*
  • Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho,Midori-ku, Yokohama 226-8503, Japan   Email: sfuse@res.titech.ac.jp   Email: hiro@res.titech.ac.jp
Further Information

Publication History

Received: 28 February 2017

Accepted: 17 March 2017

Publication Date:
18 April 2017 (eFirst)

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 SEAr reactions and C–H direct arylations, towards the step-by-step multifunctionalization of isoxazoles.

1 Introduction

2 SEAr 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