Hydrocyanation, stereospecific

This process is superior to classical hydrocyanation methods using an alkali metal cyanide6 and to the improved method using potassium cyanide and ammonium chloride4 with respect to reactivity, stereospecificity, and absence of side reactions. Also, the process is applicable fo conjugate hydrocyanation of... 

The interaction of unsaturated molecules, for example olefins and acetylenes, with transition metals is of paramount importance for a variety of chemical processes. Included among such processes are stereospecific polymerization of olefin monomers, the production of alcohols and aldehydes in the hydroformylation reaction, hydrogenation reactions, cyclo-propanation, isomerizations, hydrocyanation, and many other reactions. 

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]. 

The stereoselectivity of the reaction was the target of several investigations. The results clearly establish that the addition of hydrogen cyanide to olefins is stereospecifically syn [33, 46 9]. Thus, reaction of terminal, deuterium-substituted olefins yields the corresponding syn addition products. Hydrocyanation of 4-t-butyl cyclohex-1-ene with deuterium cyanide confirmed these results. It is found that the stereospecifity is independent of the catalyst metal employed, since both nickel° and palladium catalysis give the syn addition products [50]. 

In the hydrocyanation of alkynes containing heteroatoms in the side chain, the branched isomer predominates unexpectedly. In a series of reactions with alkyne ethers 37, chelative reaction control is observed. Thus, a reaction pathway is entered, directing to the formation of the nitriles 38 with the cyano group attached to the carbon next to the oxygen-carrying carbon. Further treatment of the reaction products with aqueous acid yields the stereospecifically substituted methylene y-lactones 39a (eq. (10)). Alternatively acetone cyanohydrin can be used as a source of HCN [61]. 

Among stereospecific chemical methods, asymmetric hydrogenation, hydroformylation, hydrocyanation, and isomerization offer some of the potentially most economic routes. As long as the substrate is relatively accessible and the turnover number is high, low costs are achievable. Development times are usually not unduly excessive. Catalyst availability is becoming less of an issue as some patent holders are now prepared to license out for specific applications. Thus, there is a wider choice of potential sources, such as Bayer, Chiroscience, and NSC Technologies. 

Incomplete and, compared to hydrocyanation of the same substrate, lower regio- and stereospecificity is found in rhodium-catalyzed hydroformylation of 4-ferr-butylcyclohexene, giving the regioisomeric 3- and 4-iert-butylcyclohexanecarbaldehydes with equatorial aldehyde groups being preferred over the corresponding axial products by a ratio of 9 1 80. 

This type of alkynol ether hydrocyanation gives rise to a new stereospecific route to a-alkyli-dene y-lactones. Acidic hydrolysis and cyclization of some of the products obtained, as above, give a-alkylidene-y-lactones in 65-83% yield with the double-bond geometry predetermined via stereoselective hydrocyanation2T... 

Z)-Alk-2-enenitriles are also available from the hydrocyanation of acetylenes, which occurs with cis stereospecificity when catalysed by a nickel(O) complex, and from the stereoselective cyanation of vinyl halides, catalysed by tetracyano-cobaltate(i). The latter procedure is equally applicable to the stereoselective synthesis of the corresponding ( )-isomers. Also, the ( )- and (Z)-isomers (17) and (18) react with piperidine with retention of configuration to provide (19) and (20) respectively (Scheme 30). In contrast, the corresponding reaction with sodium methoxide gives rise to the (Z)-isomer only. 

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