Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons.

Goki Hirata,Reina Hara,Naoya Tsubaki,Yu Yamane,Takashi Nishikata

doi:10.3762/bjoc.16.45

Abstract

A terminal alkyne is one of the most useful reactants for the synthesis of alkyne and alkene derivatives. Because an alkyne undergoes addition reaction at a C–C triple bond or cross-coupling at a terminal C–H bond. Combining those reaction patterns could realize a new reaction methodology to synthesize complex molecules including C–C multiple bonds. In this report, we found that the reaction of 3 equivalents of terminal alkyne 1 (aryl substituted alkyne) and an α-bromocarbonyl compound 2 (tertiary alkyl radical precursor) undergoes tandem alkyl radical addition/Sonogashira coupling to produce 1,3-enyne compound 3 possessing a quaternary carbon in the presence of a copper catalyst. Moreover, the reaction of α-bromocarbonyl compound 2 and an alkyne 4 possessing a carboxamide moiety undergoes tandem alkyl radical addition/C–H coupling to produce indolinone derivative 5.

Highlights

Terminal alkynes are undoubtedly useful functional groups for organic synthesis, and they can undergo a variety of reactions [1]
The C–C triple bond of an alkyne is suitable for addition reactions, whereas the terminal hydrogen atom is a good target for cross-coupling by using Sonogashira and related coupling reactions [2,3,4]
We postulated that if we could control the reactivities of the alkynyl–Cu and ATRA adducts, a tandem tertiary alkylation followed by an alkynylation could occur to produce a 1,3-enyne possessing a quaternary carbon center with good regio- and stereoselectivity (Scheme 1, this work)

Summary

Introduction

Terminal alkynes are undoubtedly useful functional groups for organic synthesis, and they can undergo a variety of reactions [1]. There are many reports on alkyne transformations, one recent development in this area has been the reaction of alkynes with tertiary alkyl electrophiles to produce functionalized quaternary carbon atoms via addition [5,6,7,8,9,10] or coupling [11,12,13,14,15,16]. We have prepared quaternary carbon centers via radical reactions by using α-bromocarbonyl compounds (a tertiary alkyl source) and olefins or heteroatoms in the presence of a copper catalyst [17,18,19].

Results

Conclusion