Carbocyanation reaction

Given a number of examples of stoichiometric studies on the oxidative addition of C-CIN bonds to nickel(O), nickel catalysts were envisaged to catalyze the carbocyanation reaction. Indeed, aryl cyanides add across alkynes in the presence... 

The scope of nitriles for the carbocyanation reaction of alkynes can be expanded by cooperative nickel/Lewis acid catalysis. Alkenyl [80, 81] and alkynyl cyanides [83, 84] also participate in the addition reaction to give highly conjugated nitrile products by nickel/BPh3 catalysis (Scheme 27). The use of aluminum-based Lewis acids causes isomerization of the double bond of alkenylcyanation products, whereas alkynylcyanation is sluggish with the aluminum reagents. 

In 2004, Nakao and Hiyama developed the first general method for the carbocyanation reaction [46] for example, the reaction of aryl cyanide 73 with alkyne 74 in the presence of Ni(cod)2/PMe3 deUvers the nitrile 75 (Eq. (6.18)) [47]. 

An additional benefit of using a Lewis acid cocatalyst in the carbocyanation reaction is that it enables the use of compounds with less reactive C(sp )-CN bonds. Aliphatic nitriles that bear no P-hydrogens, such as (substituted) acetonitrile [52], benzyl [53], and allyl cyanides [54], can be used successfully. Moreover, P-hydrogen-containing aliphatic nitriles also effectively furnish the carbo-cyanated product when the substrate has a suitable Lewis basic moiety at the y-position, as in 79 (Scheme 6.17) [55]. Intramolecular coordination of the Lewis basic group effectively suppresses undesired P-hydrogen elimination from intermediate 80. 

In relation to carbocyanation reactions, an intriguing reaction that involves the cleavage of both C-CN and C-C=0 bonds was reported. The aimulation of nitrile 86 with an alkyne can be catalyzed by nickel/Lewis acid catalyst to deliver heterocycle 87 via loss of Ar-CN (Eq. (6.23)) [62]. 

Nakao and Hiyama et al. developed nickel-catalyzed carbocyanation reactions of alkynes and alkenes [16], and extended the method to the asymmetric... 

An analogous hexahydropyrrolo [2,3- ] indole was also synthesized by a palladium-catalyzed enantioselective intramolecular cyanoamidation reaction of alkenyl cyanoformamides [18]. The nickel-catalyzed carbocyanation reactions of unsaturated carbon-carbon bonds were employed also in the synthesis of (-)-eptazocine [17], plaunotol [19], and pregabalin [20]. 

The focus of this review is to discuss the role of Cinchona alkaloids as Brpnsted bases in organocatalytic asymmetric reactions. Cinchona alkaloids are Lewis basic when the quinuclidine nitrogen initiates a nucleophilic attack to the substrate in asymmetric reactions such as the Baylis-Hillman (Fig. 3), P-lactone synthesis, asymmetric a-halogenation, alkylations, carbocyanation of ketones, and Diels-Alder reactions 30-39] (Fig. 4). 

A new Ni-catalysed carbocyanative cyclization of allene-ynes and bis-allenes has been reported. The reaction starts with the regioselective hydronickelation of the allene moiety, which is followed by cyclization via carbometalation. ... 

If the metal cyanide complex 71 formed via oxidative addition of a C-CN bond can undergo the addition across unsaturated molecules and subsequent reductive elimination, a new nitrile 72 is produced (Scheme 6.14) This process is best described as carbocyanation since the transformation enables the simultaneous introduction of an R group and a cyano group in the it-system. The reaction shown in Scheme 6.12 [37] formally falls into this class of transformation, although it proceeds through a completely different mechanism from that depicted in Scheme 6.14, and thus has a limited reaction scope. 

The nickel-catalyzed carbocyanation of alkyne 74 with alkynyl cyanide 76 was accomplished using BPhg as the cocatalyst to produce 77. On the other hand, [2+2+2] trimerization of 74 predominated to form 78 when the reaction was conducted in the absence of BPhg (Scheme 6.15) [50]. An alkynylnickel complex formed via oxidative addition of BPhg-activated alkynyl cyanide has been identified. 

The use of AlMe2Cl as a cocatalyst enables the intramolecular carbocyanation of alkenes which are too unreactive to undergo carbocyanation. It was shown that the turnover-limiting step of this reaction is not oxidative addition of a C-CN bond, but insertion of a tethered alkene [51]. A catalytic asymmetric variant of the reaction was also developed, generating valuable synthetic intermediates containing all-carbon quaternary stereogenic centers (Scheme 6.16) [51, 57]. 

---