Nickel/Lewis Acid-Catalyzed Carbocyanation of Alkynes Using Acetonitrile and Substituted Acetonitriles

Abstract

Nickel/Lewis acid dual catalysis is found to effect the carbocyanation reaction of alkynes using acetonitrile and substituted acetonitriles to give a range of variously substituted acrylonitriles. The addition of propionitrile across alkynes is also demonstrated briefly to give the corresponding ethylcyanation products in good yields, whereas the reaction of butyronitrile gives significant amounts of hydrocyanation products due possibly to ¢-hydride elimination of a propylnickel intermediate. The reaction of optically active ¡-phenylpropionitrile suggests a reaction mechanism that involves oxidative addition of a CCN bond with retention of its absolute configuration.Stereoselective construction of polysubstituted alkenes has been a major subject in organic synthesis.1 To this end, we 2 and others 3 have demonstrated carbocyanation reaction 4 of alkynes catalyzed by nickel or palladium as a new entry to stereochemically well-defined and atom economical protocols for the synthesis of tri-or disubstituted acrylonitriles, versatile synthetic intermediates for polysubstituted alkenes. We have recently disclosed that a Lewis acid (LA) cocatalyst significantly improves the efficiency of the nickel-catalyzed carbocyanation of unsaturated bonds, and allows a wide variety of nitriles including aryl, 2d alkenyl, 2d alkynyl, 2e,2f and allyl 2g cyanides to participate in the reaction. We further anticipated carbocyanation using alkyl cyanides might be feasible under similar dual catalysis, because some alkyl cyanides were reported to undergo oxidative addition to nickel(0) through the activation of C(sp 3 )CN ·-bonds. 5 In this paper, we report a full scope of the carbocyanation reaction of alkynes with acetonitrile under nickel/AlMe 3 dual catalysis. The reactions of propionitrile and butyronitrile with alkynes are also described briefly. Also demonstrated is the addition reaction of substituted acetonitriles such as aryl-and silylacetonitriles as well as protected amino-and hydroxyacetonitriles to give regio-and stereoselectively a wide variety of tri-and disubstituted acrylonitriles having allylic functional groups. 6Results and Discussion Nickel/Lewis Acid-Catalyzed Carbocyanation of Alkynes Using Acetonitrile.First, we investigated the reaction of acetonitrile (1a) with 4-octyne (2a) in the presence of a nickel/LA cooperative catalyst and found that AlMe 3 , AlMe 2 Cl, and BPh 3 were effective as a LA cocatalyst. After screening several combinations of catalysts and conditions, we found that the reaction of 1a (10 mmol) with 2a (10 mmol) proceeded in the presence of Ni(cod) 2 (5 mol %), PPh 2 (t-Bu) (10 mol %), and AlMe 3 (20 mol %) in toluene at 80°C to give the corresponding cis-methylcyanation product 3aa in 71% yield after 4 h (Entry 1 of Table 1).2d Exclusive cis-addition of 1a was unambiguously confirmed by NOE experiments. In the absence of the LA cocatalyst, the methylcyanation product was not observed in any detectable amount. Use of CH 3 CN-d 3 as a nitrile substrate gave 3aa-d 3 of 99% deuterium content, sug...

Highly Chemoselective CarbonCarbon σ‐Bond Activation: Nickel/Lewis Acid Catalyzed Polyfluoroarylcyanation of Alkynes

“…We carried out competition experiments between 1 b and 4 for the oxidative addition and the following insertion of 4octyne [Eq. (5)]. Oxidative addition at 22 8C for 1 h resulted in the sole formation of cis-7 a.…”

Shuttle Catalysis—New Strategies in Organic Synthesis

“…In this isodesmic process, the forward reaction is driven to completionb yt he releaseo f volatile isobutene as ab y-product. Lewis acidic AlMe 2 Cl is required for efficient andr eversibleo xidative addition of the C(sp 3 )ÀCN bond, [10] and DPEphos provided the greatest yield of product among the phosphine ligands evaluated. Te rminal alkenes generally afforded the linear alkyl cyanide in good yield and the reactiona lso tolerated internal alkenes, although examples were limited to substrates in which isomerization is not an issue.…”

“…To circumvent this issue, the authors employed an excesso fa lkyne or Initial work explored the feasibility of this strategy by looking at the coupling of 2-cyanostyrenes with various alkynes, which are more potent HCN acceptors (Scheme 17). [9,10] In this cascade reaction, oxidative addition of the CÀCN bond is followed by insertion across the alkyne and subsequent intramolecular insertion across the alkene thusp roducing the benzofulvene product after b-hydride elimination. The H-Ni II -CN species formed then reacts with af urther equivalent of the alkyne to regenerate the active Ni 0 catalyst.…”

Triphenylboron

“…The addition of alkynyl nitriles across alkynes to form conjugated enyne nitrile products is also best catalyzed by a combination of a nickel and triphenylboron cocatalyst system. 37 The desired methylcyanation product is not observed in the absence of the Lewis acid cocatalyst. 42, 35 The addition of triphenylboron prevents cyclotrimerization 43 and results in efficient formation of the desired enyne products (54-95% yields, eq 11).…”