Conjugate hydrocyanations

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... 

In the conjugate hydrocyanation of (-)-carvone (79), Djerassi and co-workers (32) observed the formation of the axial cyanoepimer 80 as the major prod-uct. Similarly, Alexander and Jackson (33) found that substrate 81 gave p... 

Conjugate hydrocyanation of oc -unsaturated carboxylic esters, acid chlorides, and acyl cyanides, is effected by reaction with diethylaluminium cyanide [e.g. (128) — (129)]. The acid chloride and cyanide are the most reactive. A double conjugate addition of nitromethane with a 2-methylene-4-en-3-one (130) gave a... 

Nagata, W., Yoshioka, M. Hydrocyanation and its application to steroid syntheses. Proc. Int. Congr. Horm. Steroids, 2nd 1967, 327-335. Nagata, W., Okumura, T., Yoshioka, M. Hydrocyanation. VIII. Conjugate hydrocyanation of steroidal a,P-unsaturated carboxylic acid derivatives. J, Chem. Soc. C. 1970, 2347-2355. 

Yadav et al. have developed the first example of ionic liquid-promoted one-pot oxidative conjugate hydrocyanation of MBH adducts with trimethylsilyl cyanide (TMSCN) (Scheme 3.210). This reaction involves an efficient regio-selective addition of TMSCN to p-keto-a-methylenes and ( )-cinnamaldehydes, obtained from oxidation of MBH adducts with IBX/[bmim]Br or isomerization-oxidation with NaN03/[Hmim]HS04, respectively, to afford the corresponding thermodynamically more stable p-cyanated products 468 and 469. ... 

The conjugate hydrocyanation of rather unreactive chalcone-type enones RCH=CHCOAr, employing benzophenone cyanohydrin Ph2C(CN)OH as a precursor of HCN, and catalysed by the sodium salt generated in situ from NaNH2 and the... 

Lewis Acid. Ex M-Hydrogen Cyanide and Diethylabiminum Cyanide are two optional reagents for conjugate hydrocyanation of a,(3-unsaturated ketones. The results from these two... 

The hydrocyanation of conjugated carbonyl compounds is a related reaction.83 Very often such a conjugated addition is carried out in aqueous conditions. For example, in the pioneer work of Lapworth, hydrocyanation of activated olefins was carried out with KCN or NaCN in aqueous ethanol in the presence of acetic acid (Eq. 10.36).84... 

Hydrocyanation of aliphatic conjugated dienes in the presence of Ni(0) complexes gives diene rearrangement products and /i.y-unsaUiratcd nitriles in 10-90% yields10. Dienes other than 1,3-butadiene do not produce terminal nitriles, implying that the more highly substituted jr-allyl nickel complex is favored. Thus, reaction of 1-phenylbuta-l,3-diene (1) affords ( )-2-methyl-4-phenylbut-3-enenitrile (2) as the sole product (equation 5). The... 

New catalyst design further highlights the utility of the scaffold and functional moieties of the Cinchona alkaloids. his-Cinchona alkaloid derivative 43 was developed by Corey [49] for enantioselective dihydroxylation of olefins with OsO. The catalyst was later employed in the Strecker hydrocyanation of iV-allyl aldimines. The mechanistic logic behind the catalyst for the Strecker reaction presents a chiral ammonium salt of the catalyst 43 (in the presence of a conjugate acid) that would stabilize the aldimine already activated via hydrogen-bonding to the protonated quinuclidine moiety. Nucleophilic attack by cyanide ion to the imine would give an a-amino nitrile product (Scheme 10). 

Hydroboration, 13, 1 Hydrocyanation of conjugated carbonyl compounds, 25, 3 Hydroformylation, 56, 1 Hydrogenation catalysts, homogeneous, 24, 1... 

Hydrocyanation of dienes, a process of industrial importance (see Section 6.2.4), yields 1,4-addition products when conjugated dienes are reacted. The addition involves ri3-allyl intermediates (19) ... 

The addition of hydrogen cyanide (HCN) to carbon-carbon double bonds activated by electron-withdrawing groups in the presence of a base as a catalyst (a variation of the Michael Reaction) has been known for a long time. Nitriles were also obtained by hydrocyanation of branched olefins, such as isobutylene and trimethylethylene, in vapor phase reactions in particular the reactions over alumina (3) and cobalt-on-alumina (4) were reported in the late 1940s and early 1950s. Addition of HCN to conjugated dienes in the presence of cuprous salts (vapor and liquid phase) was reported as early as 1947 (5). 

In a proton NMR experiment in which 1,4-pentadiene was added to a solution of HNi[P(OMe)3]4, it was possible to watch the isomerization of 1,4- to 1,3-pentadiene, followed by formation of l,3-dimethyl-7t-allyl complexes (53). The observation of 7t-allyl products in the reaction of the hydride with the conjugated diene, but not in the ff-alkyl intermediates involved in isomerization, illustrates the much greater stability of zr-allyl complexes of nickel compared to tr-alkyls, a feature which is also observed in the hydrocyanation reactions. 

The isomerization of the internal olefin 3PN to the terminal olefin 4PN is a critical step in the hydrocyanation of 3PN to ADN [Eqs. (9) and (10)]. Unfortunately, there is a loss in yield because the undesirable conjugated isomer 2PN is also produced. Observations discussed below have led us to the belief that cationic nickel-hydride complexes, HNiL4, may be important in the isomerization process. 

Stereoelectronic effects should also play an important role in the nucleophilic 1,4-additions of anions to conjugated systems. These effects should therefore influence the Michael reaction as well as the hydrocyanation of a,6-unsaturated ketones. Studies on these reactions provided evidence that the kinetically controlled addition of a nucleophile to a cyclohexenone derivative is indeed subject to stereoelectronic effects. 

Interestingly, the hydrocyanation of 4-t-butylcyclohexenone gave, as the kinetic product, not the cis (124) but the trans cyanoketone 123. We have seen that there is good evidence that stereoelectronic effects play an important role in the hydrocyanation of conjugated ketones. Consequently, this result can be explained by the above steric argument on the basis of which the formation of the cis isomer 124 is disfavored. 

Nagata, W. Voshioka, M. "Hydrocyanation of Conjugated Carbonyl Compounds in Organic Reactions" Wiley New York, N.Y., 1977, 25, 255. 

W. Nagata, M. Yoshioka, Hydrocyanation of Conjugated Carbonyl Compounds, Org. React. 1977, 25, 255-476. 

The hydrocyanation of conjugated dienes (e.g., butadiene) probably proceeds through the coordination of the diene and formation of a rr-allyl-typc intermediate througlt a r/s-rear ran genie nt of the nickel hydride followed by reductive elimination of the nitrile. 

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