Highly Efficient CuBr‐Catalyzed Cross‐Dehydrogenative Coupling (CDC) between Tetrahydroisoquinolines and Activated Methylene Compounds

Abstract

A novel and efficient C–C bond‐formation method was developed: the cross‐dehydrogenative coupling (CDC) reaction catalyzed by copper bromide in the presence of an oxidizing reagent, tBuOOH. The CDC reaction provides a simple and efficient catalytic method to construct β‐amino diesters and β‐dicyano amines by a combination of two different sp3 C–H bonds followed by C–C bond formation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Cu-catalyzed cross-dehydrogenative coupling: A versatile strategy for C–C bond formations via the oxidative activation of sp 3 C–H bonds

“…The direct utilization of only C-H bonds represents the next generation of C-C bond formations and is highly desirable because such a coupling will avoid the preparation of functional groups to make synthetic schemes shorter and more efficient (24). On the basis of these advances, we recently developed a Cu-catalyzed cross-dehydrogenative coupling (CDC) methodology to construct functional molecules by directly using two different C-H bonds [Scheme 1, Path C (25)(26)(27)(28)(29)]. In this work, we will present a detailed description of this method.…”

Beyond Traditional Cross Couplings: The Scope of the Cross Dehydrogenative Coupling Reaction

“…Initially the reaction between isoquinolines and difluoroenol silyl ethers was investigated under the same conditions reported by Li and coworkers. [19] Under these conditions only trace amounts of the coupled product was observed, however, on reduction of the reaction temperature from 60 8C to room temperature, the yield of the coupled product increased to 17 %. A further improvement to the yield was achieved when the reaction mixture was diluted with dichloromethane and the amount of difluoroenol silyl ether was increased to 3 equivalents, giving the coupled product in a 98 % yield.…”

“…Li and co-workers have reported several examples of (sp 3 )C À A C H T U N G T R E N N U N G (sp 3 )C CDCs using unfunctionalized starting materials. [9,19,20] The first report of a CDC between a (sp 3 )CÀA C H T U N G T R E N N U N G (sp 3 )C was achieved to yield Aza-Henry-type products, that is, b-nitroamine derivatives, Scheme 12. [20] Various copper(I) and (II) salts were investigated under the reaction conditions, however, copper(I) and (II) bromide were the most efficient.…”

“…3 )C coupling of isoquinolines with dialkymalonates has previously been reported using TBHP as the oxidant in the presence of copper(I) bromide (5 mol %), Scheme 15. [19] Various solvents were screened under the reaction conditions, including H 2 O, THF, DMSO, DCM, MeCN, and tBuOH, however, the reactions were most efficient when there was no solvent employed. Several different malonates were investigated under the reaction conditions which gave the coupled products in moderate to excellent yields.…”

“…[22] Initially the reaction was met without success when the reaction was carried out under the previously reported conditions for CÀC bond formation between isoquinoline and alkyl malonates, namely CuBr and TBHP. [19] However, when other copper sources were investigated it was found that two equivalents of copper(II) acetate gave small amounts of the coupled product. Optimization revealed that the reaction required the use of a ligand.…”