Hydrocyanation of Alkynes

Alkynes are readily hydrocyanated in the presence of a homogeneous catalyst, especially a nickel-based catalyst system. However, zerovalent palladium compounds are reported to catalyze the reaction as well, but are less efficient [60], The reaction gives an easy access to the synthetically valuable a,P-un-saturated nitriles. The use of acetone cyanohydrin as a synthetic equivalent for the difficult-to-handle HCN provides an efficient alternative, but the substrate/ catalyst ratio has to be increased in comparison with the reaction with HCN. The regioselectivity of the reaction is controlled by steric, electronic, and chelative effects. Investigations were predominantly performed by changing the substituent pattern on the acetylenic substrate [61]. 

The reaction proceeds in general stereospecifically as a cA-addition. Equation (9) shows exemplarily the addition of deutero-HCN (DCN 34) to hex-l-yne 33. The cA-position of deuterium and the cyano group is found in both branched (35) and linear (36) products. When dimethyl acetylenedicarboxylate is used as the substrate, the product of anti-addition is formed. This indicates a change in the mechanism as a result of the electron-withdrawing effect of the two functional groups in direct conjugation with the triple bond [62]. 

Steric effects, induced by the substituents of the alkyne derivative, dominate in general the regioselectivity of HCN addition when bulky alkynes are employed [63], The observed selectivity finds its analogy in the hydrocyanation of olefins already discussed. The decisive step involves formation of an -alkenyl-nickel complex. 

The regioselectivity of the hydrocyanation of alkynes is determined by both steric and electronic effects, though in most cases the steric bulk of the substrate substituent is the predominant factor of the reaction. 

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]. 

Although less studied, the hydrocyanation of alkynes in the presence of soluble transition metal complexes has also been reported. - The reactions conducted with nickel(O) catalysts occur with cis stereochemistry, high regioselectivity, and moderate-to-high yields. Again, both steric and electronic effects control the regioselectivity. These points are illustrated by the data in Equation 16.11. Terminal, straight-chain alkynes such as l-hex)me react to form predominantly the branched nitrile, whereas tert-butyl acetylene reacts to form mostly the terminal nitrile. Reactions conducted with DCN have shown that the addition occurs in a syn fashion.  

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Newer investigations deal with the conversion of a-ketoalkynes to highly functionalized 3,5-substituted 5-hydroxy-3-pyrrolin-2-ones in a regioselective synthesis with KCN catalyzed by tetracyanonickelate(O) formed in situ from the system Ni(CN)2/CO/KCN in alkaline aqueous medium. This study is based on the catalytic hydrocyanation of alkynes in the presence of Ni(CN)4" introduced by Funabiki and co-workers [66]. 

Hydrocyanation of alkynes leads stereoseleclively to a,/ -unsaturated nitriles as cur-addition products1. The incorporation of various substituents, including heterofunctions, in both the substrate and ligand has an effect on the regioselectivity and has been studied in detail. 

In conclusion, until recently asymmetric hydrocyanation was limited to only a few substrates, mainly norbornene systems, giving only low to medium asymmetric inductions. The stereoselective syn hydrocyanation of alkynes and the new results with vinylarenes, however, offer... 

The hydrocyanation of alk5mes provides a direct method for preparing a,p-unsaturated nitriles such as 67. The reactions proceed at 120 °C in an autoclave with hydrogen cyanide and catal3hic tetrakis(triphenyl phosphite)nickel(O) (Scheme 51). Lower temperatures may be employed if the aUq ne and hydrogen cyanide are added very slowly. The hydrocyanation of dienes and aUcenes (Sections 1.1.1.6 and 1.1.4.5) are much more widely used procedures than the hydrocyanation of alkynes. 

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. 

Complex (131) catalyzes the hydrocyanation of both mono- and di-substituted alkynes and, here again, cis addition of HCN occurs.604 The monosubstituted alkynes generally give linear... 

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. ... 

Substitutedacrylonitriles. A highly regioselective hydrocyanation of 1-alkynes is accomplished in two steps first by reaction with M SiCl, Nal in aqueous MeCN, and then heating with CuCN in NMP. 

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-... 

Hydrocyanation is the formal addition of hydrogen cyanide to alkenes. alkynes, and dienes to yield nitriles. These reactions can be catalyzed by various copper, cobalt, nickel and palladium catalysts modified with phosphanes and phosphites and/or Lewis acids. Hydrocyanation of carbonyl groups in aldehydes and ketones is covered in Section D.l.3.7. 

Stereoselective conversions of various terminal or phenyl-substituted internal alkynes with ether groups attached to the side chain using Ni[P(OPh)3]4 as a precatalvst give 1 89 mixtures of the regioisomers25. Hydrocyanation of aliphatic internal alkynol derivatives leads to 1 1 mixtures of both regioisomers25. 

Further studies of regioseleclive syn hydrocyanation of various alkynes and alkynols used nickel-based catalyst systems of the type NiL4 with either L = triphenylphosphite or L2 = a,a-bis(diphenylphosphino)-2-xylene (PHMEP)26. The regioselectivities observed with the phos-phane catalyst reflect dominant steric effects, whereas results with the phosphite catalyst system show some evidence for chelation control. Similar conversions of various amino alkynes also occur exclusively in a syn fashion with comparable regioselectivity trends, as in the alkynol case28. The products are used as precursors for the synthesis of saturated and unsaturated amino acids28. 

Hydrocyanation of acetylene is catalyzed by an aqueous solution of copper(I) chloride and ammonium chloride however, byproducts are also formed, viz., acetaldehyde and vinylacetylene, the latter arising by dimerization of acetylenes. Hydrocyanation, followed by reduction of alkynes leading to secondary nitriles, is catalyzed by Co(CN)5 in the atmosphere of H2 or by Ni(CN)4 in the presence of BH4 cyanide. 

In general, rhodium-catalyzed hydroformylation of alkynes proceeds much slower than the reaction with olefins. It should be remembered that homogeneously catalyzed hydroformylation of olefins with unmodified rhodium catalysts can be irreversibly poisoned by the presence of even trace quantities of alkynes. As Liu and Garland [94, 95] found by means of in situ IR spectroscopy, the reason is likely the formation of dinuclear rhodium-carbonyl complexes I, which are stable even in the presence of hydrogen (Scheme 4.17). Therefore, alternative pathways for the production of a,P-unsaturated aldehydes have been suggested, consisting of Ni-catalyzed hydrocyanation followed by chemoselective hydrogenation [96]. 

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