P-hydroxy nitriles

The DKRs of (J-azido alcohols and p-hydroxy nitriles were also accomplished hy employing 1 and CALB with PCPA as the acyl donor. The DKRs of p-azido alcohols were performed at 60°C while those of (3-hydroxy nitriles required higher temperature (100°C) primarily to enhance the racemization rate. The optical purities of products were satisfactory in all cases. In the case of p-hydroxy nitriles, dehydrogenation lowered the yield. 

Primary nitro compounds are good precursors for preparing nitriles and nitrile oxides (Eq. 6.31). The conversion of nitro compounds into nitrile oxides affords an important tool for the synthesis of complex natural products. Nitrile oxides are reactive 1,3-dipoles that form isoxazolines or isoxazoles by the reaction with alkenes or alky nes, respectively. The products are also important precursors for various substrates such as P-amino alcohols, P-hydroxy ketones, P-hydroxy nitriles, and P-hydroxy acids (Scheme 6.3). Many good reviews concerning nitrile oxides in organic synthesis exist some of them are listed here.50-56 Applications of organic synthesis using nitrile oxides are discussed in Section 8.2.2. 

Treatment of isoxazoline-fiised [60]fullerene 48 with NaOMe in the presence of MeOH gave the p-hydroxy nitrile derivative 49 in good yield <00SL361>. The synthesis of the enantiomerically pure cyclopropane amino acid 51 covalently attached to a fulleroisoxazoline has been achieved . 

Kinfe et al. (2009) report the kinetic resolution of various P-hydroxy nitriles, more specifically 3-hydroxy-4-aryloxybutanenitriles and 3-hydroxy-3-arylpropanenitriles,... 

FIGURE 17.10 Nitrile hydratase/amidase catalyzed biotransformation of O-protected P-hydroxy nitriles. 

Ankati, H., Zhu, D., Yang, Y, Biehl, R.R., and Hua, L. 2009. Asymmetric synthesis of both antipodes of P-hydroxy nitriles and P-hydroxy carboxylic acids via enzymatic reduction or sequential reduction/hydrolysis. Journal of Organic Chemistry, 74 1658-62. 

An optically active p-hydroxy nitrile with 40% ee is obtained from the reaction of LiCH2CN with PhCHO in the presence of (1). The same compound with higher ee (93% ee) is obtained using cyanomethylzinc bromide and the chiral ligand DPMPM. Amino alcohol (1) accelerates the basicity of BuLi. Thus methyl phenyl sulfide is deprotonated by BuLi in the presence of (1)... 

A wide variety of other alcohol substrates has been resolved, including aryl substituted secondary alcohols, - a-alkyl-P-hydroxy esters, P-hydroxy nitriles, and fluoroorganic compounds. Active chloroacetate esters are commonly used to speed up the hydrolysis reactions, as exemplified in eq 2 Primary acyclic alcohols possessing a stereogenic center that have been resolved include 2,3-epoxy alcohols, - 2-amino alcohols, and crown ethers. ... 

Nitrile aldol reactions. P-Hydroxy nitriles are formed in the presence of CeCl3 7H20. Addition of a chiral ligand (BINOL) increases the diastereoselectivity. 

As expected, bromoacetonitrile reacts with carbonyl compounds to give p-hydroxy nitriles. 

Openings of mcso-epoxides to obtain chiral P-hydroxy nitrile derivatives and of A -acylaziridines to afford A-(P-sulfenylalkyl) amides have enlisted the service of ligand 23 and dicyclohexyl L-(+)-tartrate, respectively. An efficient method for acquiring chiral azido silyl ethers from epoxides and Me SiN, employs a (salenlCr-N, complex 24. "... 

Reformatsky-type reagents The synthesis of P-hydroxy nitriles (9 examples,... 

P-Hydroxy nitriles, 202 7-Hydroxy nitriles, 202 N-Hydroxynorbomene-5-dicarboximide-2,3, 177... 

BackvaU et al. also reported what is described as the fastest hydrogen transfer catalyst [67, 68] that has been widely used in the DKR of secondary alcohols, P-hydroxy nitriles [69] and other important intermediates (Schemes 4.29 and 4.30) [70-74]. 

Figure 11.3 Biotransformations of p-hydroxy nitriles and analogs by nitrile hydratase and amidase in whole cells of Rhodococcus rhodochrous ATCC BAA-870 [15]. To determine the enantiomeric excess, both p-hydroxy amides and p-hydroxy acids were separately converted into the corresponding methyl ester using Fischer esterification.

Kinfe, H.H., Chhiba, V., Frederick, )., Bode, M.L., Mathiba, K., Steenkamp, P.A., and Brady, D. (2009) Enantioselective hydrolysis of p-hydroxy nitriles using the whole cell biocatalyst Rhodococcus rhodochrous ATCC BAA-870. J. Mol. Catal. B Enzym., 59, 231-236. 

Kamal, A. and Ramesh Khanna, G.B. (2001) A facile preparation of ( )-P-hydroxy nitriles and their enzymatic resolution with lipases. Tetrahedron Asymmetry, 12, 405 -410. 

Alternatively, metallated a-arylthio-nitriles undergo reaction with aldehydes and ketones to provide a-arylthio-P-hydroxy-nitriles, which are then capable of further transformation the cyanothiolacetate (13) is an attractive source of a P-hydroxypropiononitrile carbanion equivalent (Scheme 28). The p-hydroxy-nitriles (14) are also easily dehydrated, thus providing a convenient route to... 

It is known that trimethylsilyl ethers of p-hydroxy-nitriles may be obtained from epoxides and MesSiCN in the presence of AICI3 or Et2AlCl. It has now been shown that if zinc iodide is used in place of the aluminium reagent, iso-cyanides are obtained, e.g. (269) and (270). This transformation is highly... 

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