Nickel/BPh₃‐Catalyzed Alkynylcyanation of Alkynes and 1,2‐Dienes: An Efficient Route to Highly Functionalized Conjugated Enynes

Abstract

Highly substituted conjugated enynes with functional groups have gained significant importance as versatile synthetic intermediates. [1] However, conventional approaches to these structures have relied on tedious multistep sequences involving the Sonogashira coupling reaction. Transition-metal-catalyzed alkynylmetalation reactions have emerged recently as novel protocols for the construction of conjugated enyne frameworks through cleavage of a C(sp)Àm bond (m = SnBu 3[2] and B(pinacol) [3] followed by addition of the resulting alkynyl and metallic moieties across alkynes; the latter is then converted further to an organic group by subsequent cross-coupling reactions. On the other hand, to our knowledge, catalytic direct insertion of alkynes into a C(sp)ÀC bond has never been achieved. Herein, we report nickel/BPh 3 -catalyzed alkynylcyanation of alkynes and 1,2-dienes as an atom-economical and stereoselective method to access functionalized conjugated enyne structures.At the onset, we anticipated the reaction mode of alkynyl cyanides in the presence of a nickel catalyst, because electrondeficient alkynes are prone to undergo homo-and/or crosscyclotrimerization reactions under nickel catalysis.[4] Indeed, the reaction of 3-phenylpropynenitrile (1 a) with 4-octyne (2 a) in the presence of [Ni(cod) 2 ] (10 mol %) (cod = cyclooctadiene) and xantphos (10 mol %) in toluene at 100 8C for 3 h gave the expected cis-alkynylcyanation product (3 aa) in only 11 % yield and a mixture of substituted benzenes in 66 % yield which arose by trimerization of 1 a [Eq. (1)]. On the other hand, the presence of BPh 3 (30 mol %) as a Lewis acid (LA) cocatalyst [5] dramatically shifted the reaction path, [6] affording 3 aa in 69 % yield with a small amount of the benzene derivatives.We then further tested the catalysis on the reactions of various alkynyl cyanides and found that aryl-, alkenyl-, alkyl-,

Triphenylboron

“…The addition of vinyl nitriles across alkynes is efficiently catalyzed by a nickel and triphenylboron cocatalyst system (eq 10). 42, 35 The addition of triphenylboron prevents cyclotrimerization 43 and results in efficient formation of the desired enyne products (54-95% yields, eq 11). The catalyst somehow differentiates between the alkenyl-CN bonds of the starting materials and the products, but the mechanism of this selectivity is not currently well understood.…”

“…34 Unlike arylcyanation, triphenylboron is reported to be superior to aluminum based Lewis acids for the alkenylcyanation reaction. 35 Compared to other aluminumbased Lewis acid catalysts that are effective for arylcyanation reactions, 34 triarylboranes such as triphenylboron and tris(pentafluorophenyl)boron are more effective for alkynylcyanation reactions. (10) Alkynylcyanation of Alkynes and 1,2-Dienes.…”

Nickel‐Catalyzed Cascade Annulation for the Rapid Synthesis of Carbocyclic Nitriles

“…[1][2][3][4] Most notably, Nakao and Hiyama have disclosed a Nicatalyzed alkyne insertion reaction into CÀ CN bonds that can be used for the atom-economical synthesis of vinyl nitriles. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Inspired by this unique reactivity, our group has developed a host of transformations that rely on the reversibility of the CÀ CN oxidative addition step. [22 -27] This includes both nickel-catalyzed transfer hydrocyanation and aryl cyanation reactions that elude the need for toxic cyanide-based reagents such as HCN or KCN.…”

Unlocking Mizoroki–Heck‐Type Reactions of Aryl Cyanides Using Transfer Hydrocyanation as a Turnover‐Enabling Step

“…[9] Additionally,t he cyano group is unreactive under most cross-coupling conditions and can thus serve as am asked, orthogonal electrophile in as ynthetic sequence. The development of aM H-type coupling that can utilizeabroad range of cyano electrophiles [12] and alkenes has been challenging, in part because the moste fficientcatalytic protocols to activate strong CÀCN bonds towards oxidativea ddition rely on the use of aL ewis acid co-catalyst (Scheme 2b), [13] as trategy potentially incompatible with the use of bases in the traditional turnover-enabling step of the MH reaction (Scheme2a). The development of aM H-type coupling that can utilizeabroad range of cyano electrophiles [12] and alkenes has been challenging, in part because the moste fficientcatalytic protocols to activate strong CÀCN bonds towards oxidativea ddition rely on the use of aL ewis acid co-catalyst (Scheme 2b), [13] as trategy potentially incompatible with the use of bases in the traditional turnover-enabling step of the MH reaction (Scheme2a).…”