Palladium-Catalyzed Dehydrogenative C-2 Alkenylation of 5-Arylimidazoles and Related Azoles with Styrenes

Marco Lessi,Attilio Nania,Fabio Bellina,Laura Lodone,Melania Pittari,Angela Cuzzola

doi:10.3390/catal11070762

Abstract

The construction of carbon–carbon bonds by direct involvement of two unactivated carbon–hydrogen bonds, without any directing group, ensures a high atom economy of the entire process. Here, we describe a simple protocol for the Pd(II)/Cu(II)-promoted intermolecular cross-dehydrogenative coupling (CDC) of 5-arylimidazoles, benzimidazoles, benzoxazole and 4,5-diphenylimidazole at their C-2 position with functionalized styrenes. This specific CDC, known as the Fujiwara–Moritani reaction or oxidative Heck coupling, also allowed the C-4 alkenylation of the imidazole nucleus when both 2 and 5 positions were occupied.

Highlights

Transition metal-catalyzed carbon–carbon bond-forming reactions that occur by the breaking of carbon–hydrogen bonds are attracting increasing interest in modern synthetic organic chemistry since this approach does not require any pre-activation of the starting materials [1,2,3,4,5,6,7,8,9,10,11]
When compared with conventional cross-coupling methodologies that require the use of organic halides and/or preformed organometallic reagents, this strategy, known as cross dehydrogenative coupling (CDC), allows the obtainment of a high degree of atom economy and structural complexity in the target molecule, while ensuring high chemoselectivity
The palladium-catalyzed cross-coupling betweenarenes and terminal alkenes, known as the Fujiwara–Moritani reaction or even oxidative Heck coupling [12,13,14],represents one of the most classic CDC reactions for the functionalization ofarenes [2,3,4,6,11,15,16,17]. This reaction was first reported in 1967 [12], and historically precedes the development of the Mizoroki–Heck alkenylation [18,19], problems related to poor regioselectivity and the need to use oxidants have in the past limited its application in favor of both the aforementioned Mizoroki–Heck alkenylation and the traditional cross-coupling procedures, and the most recent direct alkenylation of aromatic C-H bonds, catalyzed by transition metals, involving alkenyl halides [20,21,22,23,24,25,26]

Summary

Introduction

Transition metal-catalyzed carbon–carbon bond-forming reactions that occur by the breaking of carbon–hydrogen bonds are attracting increasing interest in modern synthetic organic chemistry since this approach does not require any pre-activation of the starting materials [1,2,3,4,5,6,7,8,9,10,11]. Unlike traditional cross-couplings, the possibility of avoiding the use of metals and halogens in stoichiometric quantities reduces the production of inorganic waste In this context, the palladium-catalyzed cross-coupling between (hetero)arenes and terminal alkenes, known as the Fujiwara–Moritani reaction or even oxidative Heck coupling [12,13,14],represents one of the most classic CDC reactions for the functionalization of (hetero)arenes [2,3,4,6,11,15,16,17]. It is important to note that when the reaction is conducted using a heteroarene as a partner, the presence of one or more heteroatoms leads to an innate distinction among the different C-H bonds, allowing, with appropriate optimization of the reaction conditions, the selective involvement of a specific Csp2-H bond

Methods

Results

Conclusion