Norbomene hydrocyanation

Hydrocyanation is also catalyzed by [Pd(PPh3)4] (103) and [Pd P(OPh), 4] (132), again in both cases in the presence of excess ligand.604 Complex (132) is an effective catalyst for the addition of hydrogen cyanide to cyclic monoenes and dienes such as norbomene and norbornadiene 605-606 ethylene also reacted readily. The product obtained from norbornene was the exo isomer (equation 165). When norbornadiene was the substrate, some of the endo product was formed.605... 

In asymmetric hydrocyanation reactions the desired isomers are the chiral branched products only. Good regioselectivity toward the branched product (>98%) is limited to vinylarenes. Hydrocyanation of 1,3-dienes gives a variety of mixtures depending on the catalyst and conditions 1-alkenes give the linear nitrile as major product [34]. Both are seen in the adiponitrile process in which the unwanted branched 2M3BN (hydrocyanation product from 1,3-butadiene) is isomerized to the linear product 3-pentenenitrile, which is then hydrocyanated by in-situ isomerization to 4-pentenenitrile, resulting in the linear adiponitrile. Thus vinylarenes and cyclic alkenes (mainly norbomene) are usually the substrates of choice for the asymmetric hydrocyanation. Hopefully 1,3-dienes will become feasible substrates in the near future. 

The reaction can be carried out asymmetrically, using nickel complexes of chiral phosphite ligands. Examples are the enantioselective hydrocyanation of norbomene using ligand (22-XVIII),48 and of vinylnaphthalene derivatives with (22-XIX).49 The latter is a precursor for the anti-inflammatory drug naproxen. 

Asymmetric hydrocyanation has now been achieved using norbomene and norbomadiene as substrates. The reduction of either [PdCl2(+)-DIOP] or PdCl2 in presence of (-I )-DIOP led to a palladium(O) species formulated simply as [Pd(-l-)-DIOP]. This gave, in reaction (164), an optical yield of 30% for the 2-cxo-cyanonorbornane formed. Norbomadiene with the same catalyst gave 2-cxo-cyanonorborn-5-ene with an optical purity of 17%. When the ligand CHIRAPHOS (51) was used, the catalytic activity was greatly diminished. In addition to the review of the early work already mentioned, two more recent reviews of hydrocyanation have appeared. ... 

A number of olefins are converted in the presence of tetrakis(tri-o-tolyl phos-phite)nickel(O) into the corresponding nitriles. These additions yield the terminal nitriles predominantly [15]. Systematic investigations were performed on the hydrocyanation of olefins containing the norbomene skeleton 9 as a basic structure. Table 1 demonstrates the development of catalysts to gain stereocontrol of product formation. 

Even in the early days of homogeneous hydrocyanation the reaction of norbor-nene with hydrogen cyanide in the presence of tetrakisftriphenyl phosphite)palla-dium(O) 12 indicated the influence of steric factors, since exo-5-cyanobicy-clo[2.2.1]heptane (Structure 10) is obtained stereospecifically. This result was confirmed in similar reactions showing that the entering cyano group is directed into the exo-position of the norbomene system [28]. This is due to the complexa-tion of the palladium(O) center to the exo-face of norbomene. Recent experiments have also utilized the bicyclic system to demonstrate asymmetric hydrocyanation induced by chiral palladium diphosphine complexes. Depending on the applied ligand system 11-17, an enantiomeric excess (ee) up to 40% is obtained [25]. 

If a vinylic double bond is connected to the bicyclic skeleton of norbomene, a competition experiment shows that under the conditions employed hydrogen cyanide addition proceeds only at the endocyclic strained double bond. It is also noted that isomerization of the exocyclic olefinic bond may take place in the course of the reaction [22, 23, 37]. These experiments already reveal the most important features of homogeneously catalyzed hydrocyanation - the influence of the steric structure of the substrate and the fact that the catalyst also promotes isomerizations (cf. Section 2.5.5.1). 

A chelating diphosphite prepared from biphenol and PCI3 provides a very stable Ni(0) complex that catalyzes the hydrocyanantion of butadiene without excess ligand. Although the stability of this catalyst is enhanced, the amount of butadiene dimerization byproducts is significant. A related nickel catalyst prepared using a chiral chelating diphosphite based on I -2,2 -binaphthol provides enantioselectivity in the hydrocyanation of norbomene. The major product, J -exo-2-cyanonorbomane, was obtained in an enantiomeric excess of up to 38%. 

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. ... 

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