Reactions hydrocyanation

Nickel plays a role in the Reppe polymeriza tion of acetylene where nickel salts act as catalysts to form cyclooctatetraene (62) the reduction of nickel haUdes by sodium cyclopentadienide to form nickelocene [1271 -28-9] (63) the synthesis of cyclododecatrienenickel [39330-67-1] (64) and formation from elemental nickel powder and other reagents of nickel(0) complexes that serve as catalysts for oligomerization and hydrocyanation reactions (65). 

Starting from enantiomerically pure 4-methylsulfanyl-mandelonitrile, thiamphenicol and florfenicol have been enantioselectively synthesized (Figure 5.14). The enantiomerically pure 4-methylsulfanyl-mandelonitrile was obtained by hydrocyanation reaction of 4-methy lsulfany 1-benzaldehyde catalyzed by (M)-hydroxynitrile lyase of Badamu (almond from Xinjiang, China) (Prunus communis L. var. dulcis Borkh), which, after an extensive screening, was found to be a highly effective bio-catalyst for this reaction [85]. 

Gerrits, P.J., Zumbragel F. and Marcus, J. (2001) Analyzing the hydrocyanation reaction chiral HPLC and the synthesis of racemic cyanohydrins. Tetrahedron, 57, 8691-8698. 

Nickel is frequently used in industrial homogeneous catalysis. Many carbon-carbon bond-formation reactions can be carried out with high selectivity when catalyzed by organonickel complexes. Such reactions include linear and cyclic oligomerization and polymerization reactions of monoenes and dienes, and hydrocyanation reactions [1], Many of the complexes that are active catalysts for oligomerization and isomerization reactions are supposed also to be active as hydrogenation catalysts. 

Isomerisation is also an important step in the DuPont process for making adiponitrile (Chapter 11) in which internal pentenenitriles must be converted to the terminal alkene. The catalyst is the same as that used for the hydrocyanation reaction, namely nickel(II) hydrides containing phosphite ligands. 

Whereas many nickel-catalyzed olefin hydrocyanation reactions may be run in the batch mode (i.e., all reagents charged to the vessel at the beginning of reaction), it is often preferable to feed one or more components in a... 

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. 

Contrary to this bicyclic series, the equilibration of the a- and the b-cyano isomers derived from the steroid enones 92 (R=H or CH3) does not occur. It has also been impossible to produce the B-cyano isomer from the hydrocyanation reaction. This result was explained by the fact that in the steroid series, there is a strong steric interaction between the cyano group and the C-ll methylene group of ring C in the boat-like conformation 95 (cf 98). Consequently, addition to the B-face never occurs in these compounds. This was confirmed by the fact that 1a-cyanocholestanone (derived from 92, [KH3) readily incorporates labeled cyanide (13C=N) under the experimental conditions of the hydrocyanation reaction. 

The Strecker reaction [1] starting from an aldehyde, ammonia, and a cyanide source is an efficient method for the preparation of a-amino acids. A popular version for asymmetric purposes is based on the use of preformed imines 1 and a subsequent nucleophilic addition of HCN or TMSCN in the presence of a chiral catalyst [2], Besides asymmetric cyanations catalyzed by metal-complexes [3], several methods based on the use of organocatalysts have been developed [4-14]. The general organocatalytic asymmetric hydrocyanation reaction for the synthesis of a-amino nitriles 2 is shown in Scheme 5.1. 

Extension of this reaction toward a one-pot asymmetric Mannich-hydrocyanation reaction sequence was also reported by the Barbas group [29]. In this one-pot two-step process proline-catalyzed asymmetric Mannich reaction of unmodified aldehydes with the a-imino glyoxylate was performed first, then diastereoselective in situ cyanation. The resulting /i-cyanohydroxymethyl a-amino acids were obtained with high enantioselectivity (93-99% ee) [29]. Another one-pot two-step reaction developed by Barbas et al. is the Mannich-allylation reaction in which the proline-catalyzed Mannich reaction is combined with an indium-promoted allylation [30], This one-pot synthesis was conducted in aqueous media and is the first example of a direct organocatalytic Mannich reaction in aqueous media [28, 30]. 

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 poor turn-over numbers (TON) in the hydrocyanation reactions are another limitation, because of degradation of the catalyst, which still has to be overcome. The maximum TON reached so far have been in the order of 500-750, which is extremely low compared with other homogenous catalytic reactions. 

The hydrocyanation reactions of electrophilic aldehydes, ketones and their corresponding imines gives direct access to synthetic derivatives of several important structures, including a-hydroxy carboxylic acids, / -amino alcohols and a-tertiary and a-quaternary-a-amino acids. The asymmetric hydrocyanation reaction provides access to chiral synthons, which have proven useful for the construction of many structurally complex and biologically active compounds. Catalysis of these reactions is especially attractive with respect to avoiding the cost and relative chemical inefficiency associated with the use of chiral auxiliaries. 

The hydrocyanation reaction is important not only because it is practiced industrially on a large scale, but also because it clearly illustrates some of the fundamental postulates of homogeneous catalysis. The potential of the hydrocyanation reaction in asymmetric catalysis has also been explored and appears to be promising (see Chapter 9). 

In the hydrocyanation reaction, what are the products of Markovnikov and anti-Markovnikov additions Although 2PN is thermodynamically about 50 times more stable than 4PN, how in the isomerization of 3PN to 4PN is its formation avoided ... 

The alternative potential synthetic routes for the drug Naproxen neatly illustrate the industrial significance of asymmetric hydroformylation and asymmetric hydrocyanation reactions. This is shown in Fig. 9.12. Regio- and en-antioselective hydroformylation or hydrocyanation of 6-methoxy 2-vinyl naphthalene can give the desired enantiomers of the branched aldehyde or nitrile. These two intermediates can be oxidized or hydrolyzed to give 5-Naproxen. 

Successful development of the asymmetric hydrocyanation reaction may provide a versatile route to chiral nitriles, amines, and acids. As we have seen, the mechanistic details of the hydrocyanation reaction of butadiene with zero-valent nickel complexes are well established. By using a nickel complex of a chiral bidentate phosphinite ligand, 9.53, good conversion and enantioselectiv-ity (>85% e.e.) for the hydrocyanation of 6-methoxy 2-vinyl naphthalene have been obtained. 

The aromatic substituents on the phosphorus atoms have a pronounced effect on the enantioselectivity of this reaction. Instead of CF3 groups, if the aromatic rings are substituted in the same positions by CH3 groups, the e.e. value drops by 70%. This indicates that electronic factors may play a crucial role in the enantioselection mechanism. The proposed catalytic cycle for this reaction is shown in Fig. 9.14. All the steps shown in the catalytic cycle have precedence in achiral hydrocyanation reactions (see Section 7.7). 

C. What is material, and what is the significance of the NMR data in the asymmetric hydrocyanation reaction ... 

FIGURE 22 Preparation of supramolecular catalysts for hydrocyanation reactions (82) (A) assembly of heterodimeric chelating ligands (B) structure of the optimal nickel-diphosphine complex for hydrocyanation (other ligands of the metal center are omitted for clarity) and (C) hydrocyanation of functionalized styrenes. (For a color version of this figure, the reader is referred to the Web version of this chapter.)... 

This type of reaction is now of major industrial importance because it constitutes a straiglitforward synthesis of nitriles. Wlien it is applied to a diolefm, such as butadiene, it leads to the formation of dinitriles, which are precursors of valuable monomers for the preparation of polymers (butadiene leads to adipo-nilrile. a nylon-b, fvprecursor). Du Font developed the first commercial process using butadiene and HCN for adiponitrile synthesis from butadiene, but this process does nut proceed through a hydrocyanation reaction it is. in fact, a copper-catalyzed halogenation reaction followed by a cyanaikm reaction (tquaiion (16)) of the chlorinated intermediate (Fquation (17)). 

Most homogeneous hydrogenation, hydrohalogenation, halogenation, hydroformylation, and hydrocyanation reactions are first order in the olefinic reactant. A test whether this is the case here suggests itself. A numerical work-up is shown in Table 5.3. The fractional distances from complete conversion are calculated with eqns 5.19 for all participants at all times, and values of the characteristic coefficient k are then obtained for each from eqn 5.18 (global method), with the concentrations at 20 hours taken as C". 

A number of papers have been devoted to the subject of hydrocyanation reactions which introduce a cyano-group at different positions of the steroid molecule [including C(2), C(3), C(4), C(5), C(6), C(9), C(10), C(ll), and C(16)]. "3 The reactivity during the Michael addition reactions to the conjugated enones O... 

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