Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative amination of unactivated sp(3) carbons.

Xuesong Wu,Haibo Ge,Ke Yang,Hao Sun,Yan Zhao,Guigen Li

doi:10.1038/ncomms7462

Abstract

Cobalt-catalysed sp2 C–H bond functionalization has attracted considerable attention in recent years because of the low cost of cobalt complexes and interesting modes of action in the process. In comparison, much less efforts have been devoted to the sp3 carbons. Here we report the cobalt-catalysed site-selective dehydrogenative cyclization of aliphatic amides via a C–H bond functionalization process on unactivated sp3 carbons with the assistance of a bidentate directing group. This method provides a straightforward synthesis of monocyclic and spiro β- or γ-lactams with good to excellent stereoselectivity and functional group tolerance. In addition, a new procedure has been developed to selectively remove the directing group, which enables the synthesis of free β- or γ-lactam compounds. Furthermore, the first cobalt-catalysed intermolecular dehydrogenative amination of unactivated sp3 carbons is also realized.

Highlights

Cobalt-catalysed sp[2] C–H bond functionalization has attracted considerable attention in recent years because of the low cost of cobalt complexes and interesting modes of action in the process
Synthesis of lactams via transition metal-catalysed C–H functionalization is of current research interest because of the biological importance of these molecules[43,44]
To provide a complementary method and demonstrate the feasibility of cobalt catalysis on unactivated sp[3] carbons, we carried out the study of cobalt-catalysed bidentate ligand-directed intramolecular cyclization of propanamides

Summary

Introduction

Cobalt-catalysed sp[2] C–H bond functionalization has attracted considerable attention in recent years because of the low cost of cobalt complexes and interesting modes of action in the process. Transition metal-catalysed direct functionalization of relatively unreactive C–H bonds has emerged as a major topic of research in organic chemistry[1,2,3,4,5,6,7,8,9,10,11,12,13] This method does not require the use of prefunctionalized materials, and provides an attractive alternative to traditional cross-coupling reactions. CoII or CoIII-catalysed direct C–H functionalization of azole, 2-phenylpyridine, indole and benzamide derivatives was demonstrated[27,28,29,30] In this case, the C–H bond activation process is believed to proceed through either an electrophilic aromatic substitution or concerted metalation-deprotonation pathway. A novel two-step procedure has been developed under oxidative conditions to remove the directing group, which enables an efficient access to b-lactam, g-lactam or b-amino amide derivatives

Methods

Results

Conclusion