Hydrocyanation deactivation

One role of the phosphite ligand (besides preventing catalyst deactivation) is to assist the reductive elimination step [17]. In fact, the olefin exists as an equilibrium mixture of isomers under the hydrocyanation conditions and, tlterefore, the regioselccUvity of the addition of HCN to a double bond is determined by the ulcfin insertion into the Ni—II bond and the relative rates... 

The mechanism of NiL4-catalyzed hydrocyanation (L=P(0-o-tolyl)3) of ethylene has been studied in detail, offering the advantage that olefin isomerization is avoided (cf. Scheme 1 [10]). Scheme 1 contains the main features of the process, such as oxidative addition, n- and (r-complexes, reductive elimination, and catalyst deactivation by Ni(CN)2 formation. 

In a kinetic study, the reaction was found to be first order in MVN and HCN over concentration ranges below 0.04 M in each reagent. This saturation kinetics im-pHes that the catalyst resting state shifts from Ni-[la]-(COD), 5 (Scheme 5), to either 8 or 9. Based on the known stabihty of the 18-electron allylic hydrocyanation intermediates (vide supra) and the exclusive regioselectivity of this reaction, we beheve that complex 9 is the catalyst resting state under most hydrocyanation conditions. Under these saturation conditions, a maximum activity of 2000 tuxnovers/h (turnover=mol of nitrile/mol of nickel) was observed for the Hgand la. One of the minor comphcations of the reaction is the catalyst deactivation which removes Ni(0) from the system by an oxidative addition of HCN to form Ni(CN)2. A practical consequence of this side reaction is that the catalyst life time is reduced to 700-800 turnovers, unless a fresh supply of Ni(COD)2 is introduced into the medium. 

Nickel catalysts for hydrocyanation are poisoned by the formation of dicyanide complexes, LjNifCN). The formation of this material is second order in HCN. Thus, hydrocyanation reactions are t57pically nm under conditions in which HCN is dilute. The presence of added phosphite also helps to minirnize deactivation of the catalyst. 

The very challenging reactant acrolein (R = vinyl), which deactivates the NHase, was employed to optimize the cascade methodology. The reaction had to be carried out in aqueous buffer, because the NHase did not tolerate any organic solvent and was highly sensitive to HCN [77]. Hence, the pH had to be kept at 4.0-4.5, trading off suppression of the uncatalyzed hydrocyanation against the activity of the NHase, which has pH optimum 8. Ahphatic amides could be obtained in high yield and enantiomeric excess, if a copious excess of NHase was employed, to reduce the residence time of the nitrile, with portionwise feed of HCN. 

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