Copper‐Catalyzed Stereoselective Hydroarylation of 3‐Aryl‐2‐ propynenitriles with Arylboronic Acids

Abstract

Abstract:The selective synthesis of 3,3-diarylacrylonitriles has been achieved by copper-catalyzed hydroarylation of 3-aryl-2-propynenitriles with arylboronic acids. The starting cyanoalkynes were efficiently prepared from the appropriate aromatic aldehydes and diethyl cyanomethylphosphonate in two steps. The hydroarylation of the obtained cyanoalkyne substrates proceeded in methanol at ambient temperature to produce 3,3-diarylacrylonitriles in good to high yields with excellent syn selectivity. The present method was successfully applied to the regiospecific synthesis of both stereoisomers of CC-5079, which was recently reported as a potent anticancer drug.

Rhodium‐ and Palladium‐Catalyzed Hydroarylation of Propargylic Amines with Arylboronic Acids

“…Hydroarylation of propargylic amines 2j and 2k, bearing secondary and primary propargylic groups afforded, however, product distributions (entries 9-11) similar to that observed in the presence of tertiary propargylic groups (entries [1][2][3][4][5][6][7][8]. This observation points out that, at least within the examples tested, steric effects play a minor role in controlling the reaction outcome.…”

“…The transition metal-catalyzed hydroarylation of carbon-carbon triple bonds is one of the most efficient procedures towards this goal. [1] Besides unsaturated halides/triflates [2] and arene-A C H T U N G T R E N N U N G diazonium salts, [3] organoboron reagents have gained increasing attention in the last decade as possible reagents in this methodology, due to their high stability and functional group compatibility. The rhodium-catalyzed hydroarylation of disubstituted alkynes with arylboronic acids 1 in dioxane/water was first reported by Hayashis group [4] and, since then, the reaction has been carried out in water using aza-heteroaromatic alkynes as substrates [5] and in a water-toluene biphasic system using a water-soluble ligand; [6] more recently, a phosphine-free rhodium complex has been explored as an effective catalyst.…”

Synthesis of 3‐Arylindole‐2‐carboxylates via Copper‐Catalyzed Hydroarylation of o‐Nitrophenyl‐Substituted Alkynoates and Subsequent Cadogan Cyclization

“…Our process has the advantage of being carried out using inexpensive copper(I) acetate without extra ligands and additives and being tolerant of a wide variety of functional groups under mild reaction conditions. Cu‐catalyzed hydroarylation enables the successful synthesis of biologically interesting molecules such as 4‐arylcoumarins,9b butenolides,9d pentenolides,9d and a potent anticancer agent CC‐5079 9c. In this article, we report a viable method for synthesizing 3‐arylindole‐2‐carboxylates via the Cu‐catalyzed hydroarylation of o ‐nitrophenyl‐substituted alkynoates and subsequent reductive cyclization.…”

E- and Z-, di- and tri-substituted alkenyl nitriles through catalytic cross-metathesis

“…There are catalytic approaches for stereoselective preparation of trisubstituted alkenyl nitriles but these are confined to aryl- or polyaryl-substituted products 21,24,34,35,36,37 , or demand forcing conditions (≥120 °C) 38,39 . In some instances high loadings of precious metal salts 39,40 , or excess amounts (2.0 equiv.)…”

“…The large majority of the above protocols, regardless of the degree of substitution in the product olefin, require an acetylenic compound as the starting material 22–23,25,29,35–40 ; methods that involve alkenes as starting materials would be strategically distinct and especially desirable, as olefins are more abundant and less costly.…”