Hydrocyanation Mechanism

First we will describe the hydrocyanation of ethene as a model substrate. The catalyst precursor is a nickel(O) tetrakis(phosphite) complex which is protonated to form a nickel(II) hydride. Actually, this is an oxidative addition of HCN to nickel zero. In Figure 11.1 the hydrocyanation mechanism in a simplified form is given the basic steps are the same as for butadiene, the actual substrate, but the complications due to isomer formation are lacking. 

Hydrocyanation represents a reaction of considerable economic importance largely due to the value of the DuPont process involving HCN addition to butadiene to afford adiponitrile.61,62 The mechanism is well known, and involves (i) oxidative addition of H-CN to a coordinatively unsaturated metal complex, (ii) coordination of an alkene to the H-M-CN species, (iii) migratory... 

The mechanism of the simplest reaction HCNO+ + HCN —> cvc/o-HCCHN+ + NO has been explored at the MP2/6-31G(d) level of theory. The most favorable reaction profile involves the formation of a C—N bond between the positively charged carbon atom of HCNO+ and the nitrogen atom of hydrocyanic acid giving an HCNO+/HCN intermediate which isomerizes into an ionized nitrosoazirine before losing NO. 

Figure 15 Postulated mechanism for the hydrocyanation of an o-epoxy ketone by Et2AICN.

Because of its low acidity, hydrogen cyanide seldom adds to nonactivated multiple bonds. Catalytic processes, however, may be applied to achieve such additions. Metal catalysts, mainly nickel and palladium complexes, and [Co(CO)4]2 are used to catalyze the addition of HCN to alkenes known as hydrocyanation.l67 l74 Most studies usually apply nickel triarylphosphites with a Lewis acid promoter. The mechanism involves the insertion of the alkene into the Ni—H bond of a hydrido nickel cyanide complex to form a cr-alkylnickel complex173-176 (Scheme 6.3). The addition of DCN to deuterium-labeled compound 17 was shown to take place... 

Much lower yields are achieved when terminal alkynes react with HCN. Terminal nitriles formed due to mainly steric factors are the main products. Regio- and stereoselectivities similar to those in hydrocyanation of alkenes indicate a very similar mechanism. 

Before discussing hydrocyanation chemistry we will explore the interaction of zero-valent nickel phosphite complexes with various independent components of the catalytic system. Then, in turn, we will examine the catalyzed addition of HCN to butadiene, the isomerization of olefins, and the addition of HCN to monoolefins. Finally, a summary of the mechanism as it is now understood will be presented. 

Fig. 9. Mechanism of ethylene hydrocyanation. Dashed arrows imply irreversible reactions.

The mechanism shown in Fig. 9 for the hydrocyanation of ethylene with (C2H4)Ni[PO-o-tolyl)3]2 is inconsistent with the kinetic data described above for 4PN with Ni[P(0-p-tolyl)3]4 and Lewis acid (A). This is not unreasonable when we remember that the equilibrium constant for binding of ethylene to Ni(0) is 70 times greater than that for binding of 4PN (Table II), whereas P(0-p-tolyl)3 is preferred over P(0-o-tolyl)3 by a factor of 108 (Table I) This leads to the possibility that an intermediate such as 19 is much less important in the 4PN/P(0-o-tolyl)3 system. How the Lewis acid changes the mechanism is also still not clear. 

Fig. 16. The mechanism of PN isomerization/hydrocyanation in the absence of a Lewis acid. R"Ni = NCCH2(CH3CH2)CHNi, R" Ni = NC(CH3CH2CH2)CHNi.

The stereochemistry of palladium-catalyzed hydrocyanation has been studied further using [Pd(DIOP)2] (133) as catalyst.607 It was shown that the addition of HCN to both cyclic and acyclic alkenes is cis. The mechanism is believed to be the same as for the nickel-catalyzed reaction (Scheme 58). 

In 2000, Kagan and Holmes reported that the mono-lithium salt 10 of (R)- or (S)-BINOL catalyzes the addition of TMS-CN to aldehydes (Scheme 6.8) [52]. The mechanism of this reaction is believed to involve addition of the BI NO Late anion to TMS-CN to yield an activated hypervalent silicon intermediate. With aromatic aldehydes the corresponding cyanohydrin-TMS ethers were obtained with up to 59% ee at a loading of only 1 mol% of the remarkably simple and readily available catalyst. Among the aliphatic aldehydes tested cyclohexane carbaldehyde gave the best ee (30%). In a subsequent publication the same authors reported that the salen mono-lithium salt 11 catalyzes the same transformation with even higher enantioselectivity (up to 97% Scheme 6.8) [53], The only disadvantage of this remarkably simple and efficient system for asymmetric hydrocyanation of aromatic aldehydes seems to be the very pronounced (and hardly predictable) dependence of enantioselectivity on substitution pattern. Furthermore, aliphatic aldehydes seem not to be favorable substrates. 

Over the past half-dozen years, many laboratories have focused their efforts on the development of chiral hydrogen bond donors that function as catalysts for enantioselective organic reactions. One of the earliest successes in this area came from Jacobsen and co-workers, who reported the use of peptide-like chiral urea-based catalysts for the hydrocyanation of aldimines and ketoimines [40, 41]. Several other laboratories have also reported highly enantioselective transformations catalyzed by a chiral hydrogen bond donor. The following sections provide a summary of the many developments in hydrogen bond-catalyzed enantioselective reactions, along with a discussion of mechanisms and selectivity models. 

The upper half of Figure 9.9 demonstrates that acetone can also be transformed into acetone cyanohydrin (A) by the combined treatment with sodium cyanide and ammonium chloride. Ammonium chloride is a weak acid. Consequently, the protonation of the (nonvolatile) sodium cyanide to the (volatile) hydrocyanic acid occurs to a lesser extent than with the NaCN/H2S04 method (see above). However, ammonium chloride is not acidic enough to activate acetone as the carboxonium ion to the same extent as sulfuric acid. This changes the addition mechanism. As shown in Figure 9.9, it is the cyanide anions that react with the unactivated acetone. Only when the cyanohydrin anions have thus been formed does the ammonium chloride protonate them to yield the neutral cyanohydrin. 

Large-scale manufacturing processes involving isomerization reactions by homogeneous catalysts are few. Two important ones are the isomerization step in the SHOP process and the enantioselective isomerization of diethylgeranyl or diethylnerylamine as practiced by the Takasago Perfumery. The isomerization step in the SHOP process is discussed later on in this chapter. The Takasago process is discussed in Chapter 9. Isomerization of alkenes with nitrile functionalities is very important in DuPont s hydrocyanation process. The mechanism for this reaction is discussed in Section 7.7. 

Although for clarity the reactions of Fig. 7.13 are shown to be unidirectional, all the reactions of the catalytic cycle are in fact reversible. This is an important aspect of the first stage of the hydrocyanation process. It provides for a mechanism for the isomerization of the unwanted 2M3BN to the desired 3PN. The isomerization reaction of 2M3BN to 3PN has been studied by deuteriumlabeling experiments. The results are consistent with a mechanism where butadiene is formed in one of the intermediate steps. This means that the reversibility of all the steps allows isomerization to follow the path 7.51 — 7.50 — ... 

The aromatic substituents on the phosphorus atoms have a pronounced effect on the enantioselectivity of this reaction. Instead of CF3 groups, if the aromatic rings are substituted in the same positions by CH3 groups, the e.e. value drops by 70%. This indicates that electronic factors may play a crucial role in the enantioselection mechanism. The proposed catalytic cycle for this reaction is shown in Fig. 9.14. All the steps shown in the catalytic cycle have precedence in achiral hydrocyanation reactions (see Section 7.7). 

The first mechanism is. in fact, reminiscent of the well-known copper-catalyzed dimerization of acetylene viny(acetylene being the main by-product of this process. This side reaction can, however, be inhibited to some extent by the use of cobalt salts as additives [IS]. The cyanation of acetylene and of alkenyl halides is also promoted by Co and Ni cyanides and Pd catalysis. A reducing reagent, such as Zn or NaBll4, has been used in conjunction with cobalt cyanide complexes, and the formation of. succinonitrile has been reported to result from the basebase-catalyzed hydrocyanation of acrylonitrile. 

The mechanism of hydrocyanation by nickel catalysts should proceed through a nickel hydride addition on the double bonds. The nickel hydrides should result from the oxidative HCN addition to the metal, or from the above Lewis acid-assisted dissociation of HCN. The oxidative HCN addition to low-valent metal complexes has been demonstrated, particularly by NMK spectroscopy with Ni(0)(P(OF.t)3 4. 

The proposed mechanism for copper catalyzed hydrocyanation is as follows ... 

Figure 1 Proposed mechanism of butadiene hydrocyanation with Ni catalysts showing the pathway that introduces the first CN group...

---