Hydrocyanation anti-Markovnikov addition

In the hydrocyanation reaction, what are the products of Markovnikov and anti-Markovnikov additions Although 2PN is thermodynamically about 50 times more stable than 4PN, how in the isomerization of 3PN to 4PN is its formation avoided ... 

The last steps in hydrocyanation of 1,3-butadiene involve first isomerization to 70 and then anti-Markovnikov addition of HCN to the remaining C=C bond,... 

Hydrocyanation usually leads to anti-Markovnikov addition ... 

Although anti-Markovnikov addition is favored for many olefins, significant amounts of branched nitrile products are often observed. This can be because of rapid olefin isomerization prior to hydrocyanation. For example, it is estimated that 85% of the 2-methylhexenenitrile formed in hexene-1 hydrocyanation results from direct hydrocyanation of hexene-2 and only 15% from Markovnikov addition to hexene-1 . 

The addition of HCN to C=C double bonds can be effected in low yields to produce Markovnikov addition products. However, through the use of transition metal catalysts, the selective anti-Markovnikov addition of HCN to alkenes can take place. The most prominent example of the use of aqueous media for transition metal-catalyzed alkene hydrocyanation chemistry is the three-step synthesis of adi-ponitrile from butadiene and HCN (Eqs. 5-7). First discovered by Drinkard at DuPont [14], this nickel-catalyzed chemistry can use a wide variety of phosphorus ligands [15] and is practiced commercially in nonaqueous media by both DuPont and Butachimie, A DuPont/Rhone-Poulenc joint venture. Since the initial reports of Drinkard, first Kuntz [16] and, more recently, Huser and Perron [17, 18] from Rhone-Poulenc have explored the use of water-soluble ligands for this process to facilitate catalyst recovery and recycle from these high-boiling organic products. 

The addition of HCN to C=C double bonds can be effected in low yields to produce Markovnikov addition products. However, through the use of transition metal catalysts, the selective anti-Markovnikov addition of HCN to alkenes can take place. The most prominent example of the use of aqueous media for transition metal-catalyzed alkene hydrocyanation chemistry is the three-step synthesis of adiponitrile... 

Hydrocyanation of alkenes usually gives anti-Markovnikov products. Interestingly, however, addition of HCN to styrene yields mostly the branched (Marko-vnikov) adduct. This was suggested to result from stabilization of the branched alkylnickel cyanide intermediate by interaction of nickel with the aromatic ring.176... 

The nickel-catalyzed hydrocyanation of butadiene is a two-step process (Figure 3.32). In the first step, HCN is added to butadiene in the presence of a nickel-tetrakis(phosphite) complex. This gives the desired linear product, 3-pente-nenitrile (3PN), and an unwanted branched by-product, 2-methyl-3-butenenitrile (2M3BN). The products are separated by distillation, and the 2M3BN is then isomerized to 3PN. In the second step, 3PN is isomerized to 4PN (using the same nickel catalyst), followed by anti-Markovnikov HCN addition to the terminal double bond. The second step is further complicated by the fact that there is another isomerization product, CH3CH2CH=CHCN or 2PN, which is thermodynamically more stable than 4PN. In fact, the equilibrium ratio of 3PN/2PN/4PN is only 20 78 1.6. Fortunately, the reaction kinetics favor the formation of 4PN [95],... 

Figure 7.13 First stage of hydrocyanation. Conversion of butadiene to 3PN. Under the reaction conditions 2M3BN is isomerized to 3PN. Interaction of Lewis acid with coordinated nitrile is not shown for clarity. The left and right side involve CN addition in an anti-Markovnikov and Markovnikov manner. L = P(OEt)3 or P(0-o-tolyl)3.

Hydrocyanation is the addition of HCN across a C=C bond. In 1971, Dupont reported a new process that added two equivalents of HCN, in an anti-Markovnikov manner, to 1,3-butadiene to yield adiponitrile (equation 9.38).96 The process is catalyzed overall by a Ni(0) triarylphosphite complex. 

The addition of HCN to olefins catalyzed by complexes of transition metals has been studied since about 1950. The first hydrocyanation by a homogeneous catalyst was reported by Arthur with cobalt carbonyl as catalyst. These reactions gave the branched nitrile as the predominant product. Nickel complexes of phosphites are more active catalysts for hydrocyanation, and these catalysts give the anti-Markovnikov product with terminal alkenes. The first nickel-catalyzed hydrocyanations were disclosed by Drinkard and by Brown and Rick. The development of this nickel-catalyzed chemistry into the commercially important addition to butadiene (Equation 16.3) was conducted at DuPont. Taylor and Swift referred to hydrocyanation of butadiene, and Drinkard exploited this chemistry for the synthesis of adiponitrile. The mechanism of ftiis process was pursued in depth by Tolman. As a result of this work, butadiene hydrocyanation was commercialized in 1971. The development of hydrocyanation is one of tfie early success stories in homogeneous catalysis. Significant improvements in catalysts have been made since that time, and many reviews have now been written on this subject. ... 

The catalytic cycle for the hydrocyanation of 4PN to ADN is similar to that in Figure 5.9 and is therefore not shown again. Oxidative addition of HCN to NiLj produces complex 5.56. Insertion of the double bond of 4PN in the Ni-H bond of 5.56 in an anti-Markovnikov fashion produces complex 5.66. The interaction of the bulky Lewis acid with the coordinated CN of 5.56 (not shown) ensures that 5.66 rather than the Markovnikov isomer 5.67 is selectively formed. The former... 

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