Mild Copper‐Catalyzed Vinylation Reactions of Azoles and Phenols with Vinyl Bromides

Abstract

An efficient and straightforward copper-catalyzed method allowing vinylation of N- or O-nucleophiles with di- or trisubstituted vinyl bromides is reported. The procedure is applicable to a broad range of substrates since N-vinylation of mono-, di-, and triazoles as well as O-vinylation of phenol derivatives can be performed with catalytic amounts of copper iodide and inexpensive nitrogen ligands 3 or 8. In the case of more hindered vinyl bromides, the use of the original bidentate chelator 8 was shown to be more efficient to promote the coupling reactions than our key tetradentate ligand 3. The corresponding N-(1-alkenyl)azoles and alkenyl aryl ethers are obtained in high yields and selectivities under very mild temperature conditions (35-110 degrees C for N-vinylation reactions and 50-80 degrees C for O-vinylation reactions). Moreover, to our knowledge, this method is the first example of a copper-catalyzed vinylation of various azoles. Finally, this protocol, practical on a laboratory scale and easily adaptable to an industrial scale, is very competitive compared to the existing methods that allow the synthesis of such compounds.

Copper Catalyzed C-O and C-N Coupling of Vinyl Bromides with Phenols and Azoles

“…We started using the same protocol described for the coupling of β-bromostyrene with phenols (CuI/picolinic imines and Cs 2 CO 3 ) 2 , however, to our delight the best results were obtained by using a simple and inexpensive system composed by CuI/Phenantroline and K 3 PO 4 . After optimization, the scope of reaction was extent to a variety of phenols.…”

Five‐Membered Heterocycles: 1,3‐Azoles

“…The reaction can be performed with catalytic amounts of copper iodide and inexpensive nitrogen ligands under very mild temperature conditions C) [141]. For example, the viynilation of imidazole 74 by b-bromostyrene afforded compound 87 with a yield of 93% (Scheme 10.32).…”

Copper(I) Iodide

“…(E) Vinylation Reaction: CuI, in combination with tetradendate ligand L, represents a remarkable catalyst system for vinylation reactions. 20 Under this set of conditions, both azoles and substituted phenols can be coupled with b-bromostyrene. While this protocol is effective for the vinylation of (E)-b-bromostyrene, the Z-isomer leads mainly to byproducts due to its lower reactivity.…”