Hydrocyanation of alkenes

The hydrocyanation of vinylarenes ° has been studied by a DuPont team using nickel catalysis. The hydrocyanation of 6-methoxy-2-vinylnaphthalene (2.219) affords the product (2.220), where the enantiomeric excess is strongly dependent upon the electronic nature of the bisphosphinite ligand (2.12). Hydrolysis of the nitrile (2.220) affords the nonsteroidal anti-inflammatory drug Naproxen. This nickel-catalysed procedure has also been applied with some success to the regiose-lective, asymmetric hydrocyanation of 1,3-dienes such as 1-phenyl-1,3-butadiene (2.221) to give the 1,2-adduct (2.222) with ees between 50 and 83%.  

Tang andX. Zhang, Chem. Rev., 2003,103, 3029. (f) M. KitamuraandR. Noyori, in Ruthenium in Organic Synthesis, ed. S. Murahashi, Wdey-VCH, Weinheun, 2004, 5. 

Ratovelomanana-Vidal, S. Mallart, X. Pfister, L. Bischoff, M. C. Cano de Andrade, S. Darses, C. Galopin and J. A. Laffitte, Tetrahedron Asymmetry, 1994, 5, 675. 

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Kitamura, K. Nagai, Y. Hsiao and R. Noyori, Tetrahedron Lett., 1990, 31, 549. 

The mechanism of hydrocyanation of alkenes catalyzed by soluble complexes is closely related to the mechanism of hydrogenation and hydrosilation. Hydrocyanation occurs by a sequence consisting of oxidative addition of HCN, olefin insertion into the M-H bond, and reductive elimination to form the new C-C bond. The mechanism of the original hydrocyanation catalyzed by cobalt carbonyl has not been studied in depth, but the mechanism of the reactions catalyzed by nickel complexes has been studied in depth and is better defined. 

However, Lewis acids have a pronounced effect on the regioselectivity of olefin hydro-cyanation. The Lewis acid is thought to coordinate to the cyano group, as noted in detail below. Coordination of the large BPhj increases steric constraints on the coordination sphere, and this steric effect is thought to further enhance the thermodynamic preference for formation of the terminal alkylnickel complex.  

Certain reaction conditions and properties of the nickel complexes promote hydrocyanation. The oxidative addition of HCN requires an open coordination site. Catalysts containing P(0-o-Tol)3 as ligand are particularly reactive because the imsatu-rated L Ni complex is the most stable form of the Ni(0) complex, whereas the saturated 18-electron L Ni complex is the most stable form of the catalysts containing smaller phosphite ligands. The need to imderstand the steric and electronic properties of the ligand on the dissociation of phosphine led to the classic work of Tolman on cone angles and electronic parameters.  

In the 1930s, W. H. Carothers, an American chemist, and his associates at E. I. DuPont de Nemours Company in Wilmington, Del., developed nylon, the first synthetic polymer fiber to be produced commercially in 1938. These findings laid the foundations of the synthetic-fiber industry. 

Condensation polymerization occurs between molecules of monomers by the elimination of, commonly, water but also of other small molecules. 

Thus HCN, although a weak acid, adds oxidatively to nickel phosphite compounds (NiL4), as in equation  

NiL4 + HCN NiH(CN)L2 + 2L Further reactions might include addition of the alkene  

Oxidative additions and reductive eliminations can also take place. 

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The synthesis of analogous iminoacyl complexes by isonitrile insertion into linear alkyl-zirconocene chlorides is also known. In an overall regiospecific hydrocyanation of alkenes, iminoacyls 21 derived from tBuNC or Me3SiCN (as the Me3SiNC isomer) may be treated with I2 to rapidly generate an imidoyl iodide and subsequently the nitrile 22 (Scheme 3.6) [22], Less hindered iminoacyl complexes (e. g. R = Bu, Cy) may be hydrolyzed to afford aldehydes 23 [23]. 

Regiospecific hydrocyanation of alkenes. Reaction of /-butyl isocyanide with the adducts of 1 with alkenes results in products (2) that are converted by iodine (excess) into hydrocyanides (3) and /-butyl iodide with release of ClCp2ZrI. (CH1).,SiN=C can be used in place of (CH,)3CN=C, but yields are generally lower.2... 

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... 

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. 

The hydrocyanation of alkenes [1] has great potential in catalytic carbon-carbon bond-formation because the nitriles obtained can be converted into a variety of products [2]. Although the cyanation of aryl halides [3] and carbon-hetero double bonds (aldehydes, ketones, and imines) [4] is well studied, the hydrocyanation of alkenes has mainly focused on the DuPont adiponitrile process [5]. Adiponitrile is produced from butadiene in a three-step process via hydrocyanation, isomerization, and a second hydrocyanation step, as displayed in Figure 1. This process was developed in the 1970s with a monodentate phosphite-based zerovalent nickel catalyst [6],... 

The formation of complexes with Lewis bases, especially BPh3, that is, MCNBPh3, is of importance in the hydrocyanation of alkenes by nickel complexes (Section 22-4). 

While hydrocyanation, the addition of HCN to an unsaturated substrate, is not the only method of producing an organonitrile, it is often the easiest and most economical. The addition of HCN to aldehydes and ketones is readily accomplished with simple base catalysis, as is its addition to activated aUcenes (Michael addition). However, the addition of HCN to unactivated alkenes and dienes is best accomplished with a transition metal catalyst. The hydrocyanation of alkenes and dienes is the most important way to prepare nitriles and is the focus of this article. 

Some metal complexes of metals other than nickel are known to catalyze the hydrocyanation of alkenes, among the best being those of palladium and cobalt. ... 

A method for the hydrocyanation of alkenes and alkynes is based upon hydrozirconation followed by isonitrile insertion (Scheme 13) overall yields range from 45-90%. Certain examples do not exhibit the clean regiochemistry represented here, and these were discussed in Section 3.9.3.3.2. The hydrozirco-nation/protonolysis of equation (53) results in high yield, stereoselective formation of C-methyldeoxy-sugars, an alternative to free radical deoxygenation. ... 

Hydrocyanation of alkenes and alkynes offers a direct and economical way to produce of organonitriles which can be transformed into a variety of other val-... 

Based on the extensive studies reported for the triaryl phosphite-nickel complex catalyzed hydrocyanation of alkenes [1] and our own findings, we propose a general catalytic cycle shown in Scheme 5 for the Ni(COD)2/L/MVN system. This simplified catalytic cycle is meant to encompass the various diastereomeric pathways generated by the ligand Cj symmetry. 

Several reviews compile general aspects of the applications of transition metal catalyzed hydrocyanation of alkenes and alkynes1-6. This method is synthetically interesting since, starting from nonactivated alkenes. access is achieved not only to nitriles, but also to carboxylic acid derivatives, amines and isocyanates. Of industrial importance is the double addition of hydrogen cyanide to butadienes yielding adipodinitrile7,8. 

Addition. Markovnikov hydrocyanation of alkenes is accomplished employing TsCN and PhSiH3 and a (salen)Co complex in ethanol at room temperature. 

The mechanism of the related palladium-catalyzed asymmetric hydrocyanation of alkenes has also been examined in detail using [Pd(RR-diop)(C2H4)] and related chiral species as precursor complexes. These additions gave the exo nitrile product with up to 40% enantiomeric excess, indicating stereoselective complexa-tion of norbornene to the Pd(0) via the exo face. The plausible reaction intermediates [Pd(diop)(norbornene)] and the hydrido cyanide (60) were characterized by and P NMR spectroscopy. Oxidative addition of HCN to Pd(0) is believed to precede rate-determining alkene binding. 

The hydrocyanation of alkenes and dienes has similarly provided an exceptionally useful process for the conversion of simple feedstocks into more complex structures. [Caution Hydrogen cyanide is a highly toxic gas.] The process is best known as a key step in the DuPont adiponitrile process, which involves the dihydrocyanation of 1,3-butadiene (Scheme 3-95). The overall sequence first involves butadiene hydrocyanation to afford a mixture of 3-pentenenitrile and 2-methyl-3-butenenitrile. The unwanted branched isomer 2-methyl-3-butenenitrile is isomerized to 3-pentenenitrile under different conditions, and then 3-pentenenitrile is isomerized to 4-pentenenitrile in a subsequent nickel-catalyzed process in the presence of Lewis acidic additives. Finally, hydrocyanation of the remaining alkene generates the desired product adiponitrile, which serves as a precursor for nylon. A vast number of studies describing the optimization and mechanistic study of this process has appeared, and the interested reader is referred to the many excellent studies describing the details of this process. " ... 

The hydrocyanation of alkenes is a well-studied and S5nithetically useful process.P ] A significant amount of the attention that this reaction has received is derived from its utility in the preparation of adiponitrile from butadiene (Section 1.1.1.6). A complete catalytic cycle for the hydrocyanation of alkenes is shown in Scheme 71. Steric effects in the Lewis acid promoter have been shown to affect critically the reaction selectivities.l ... 

The as5mimetric hydrocyanation of alkenes has also received considerable atten-tion.h " In a representative example by RajanBabu, the glucose-derived phosphine ligand 94 allows useful enantioselectivities to be obtained in the hydrocyanation of aiyl-substituted alkenes (Scheme 72). 

The enantioselective hydrocyanation of alkenes has the potential to serve as an efficient method to generate optically active nitriles, as well as amides, esters, and amines after functional group interconversions of the nitrile group. As in asymmetric hydroformylation, asymmetric hydrocyanation requires control of both regiochemistry and stereochemistry because simple olefins tend to generate achiral terminal nitrile products. The hydrocyanation of norbomene will give a single constitutional isomer and was studied initially. However, modest enantioselectivities were obtained, and the synthetic value is limited. ... 

Tauchert, M.E. (2013) Hydrocyanation of alkenes, in C-1 Building Blocks in Organic Chemistry (ed P.W.N.M. van Leeuwen), Georg Thieme Verlag KG, 2014 in press. 

Alkyl nitriles are also prepared from alkyl halides with sodium cyanide impregnated on alumina and with cyanide ion in the presence of polystyrene-bound n-propyltributylphosphonium bromide, and by hydrocyanation of alkenes and alkynes. ... 

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