Acrylamides, enantioselective

A biphenyl and ct-methylnaphthylamine-derived chiral quaternary ammonium salt 23d, which was shown by Lygo to be effective for the asymmetric alkylation of Schiffs base 20, was also effective in the Michael reaction (Scheme 7.12) [43]. Notably, the enantioselectivity was highly dependent on the reaction conditions and substrates used. The Michael reaction of imine esters such as benzhydryl and benzyl esters with a,p-unsaturated ketones under solid-liquid phase-transfer catalysis conditions afforded the Michael adduct in up to 94% ee and 91% ee, respectively, while the tert-butyl ester showed moderate enantioselectivity (Scheme 7.12). Interestingly, in contrast to earlier reports, acrylate [42] and acrylamides failed to undergo the Michael reaction under these optimized conditions. 

In basic chemicals, nitrile hydratase and nitrilases have been most successful. Acrylamide from acrylonitrile is now a 30 000 tpy process. In a product tree starting from the addition of HCN to butadiene, nicotinamide (from 3-cyanopyridine, for animal feed), 5-cyanovaleramide (from adiponitrile, for herbicide precursor), and 4-cyanopentanoic acid (from 2-methylglutaronitrile, for l,5-dimethyl-2-piperidone solvent) have been developed. Both the enantioselective addition of HCN to aldehydes with oxynitrilase and the dihydroxylation of substituted benzenes with toluene (or naphthalene) dioxygenase, which are far superior to chemical routes, open up pathways to amino and hydroxy acids, amino alcohols, and diamines in the first case and alkaloids, prostaglandins, and carbohydrate derivatives in the second case. 

Metal-bis(oxazoline) complexes were widely used as effective catalysts for enantioselective Diels-Alder reactions. Two research groups could achieve excellent diastereo- and enantio-selectivity for the reaction of cyclopentadiene (54) and the acrylamide 55 (Fig. 9) [27]. Yet the decisive feature is only recognizable when both studies are analyzed together. In both cases the endo products are obtained in high selectiv-ities using either the magnesium- or the copper-containing catalyst. However, despite the same... 

Enantioselective packings Polar or nonpolar Packings with enantioselective cages or enantioselective surfaces, microcrystalline cellulose triacetate, cellulose ester or cellulose, carbamate/sil-ica composites, optically active poly(acrylamide)/silica composites, chemically modified silicas (Pirkle phases), cydodextrine modified silicas Operated either with normal phase or reversed phase mobile phases... 

The reaction of 77 and a,P-disubstituted acrylamides 78 mediated by Cu(OTl)2-79 afforded C-4 disubstituted isoxazolidines 80 with good diastereo- and enantioselectivity. In this case, the N-H imide template was chosen to accomplish rotamer control and improve... 

One of the most studied polymerization systems employs alkyllithium initiators that are modified by chiral amine ligands for the polymerization of sterically bulky methacrylates [8,38,39,40,41], acrylates [42],crotonates [43], and acrylamides [44]. A primary example is the reaction of triphenylmethyl methacrylate with an initiator derived from 9-fluorenyllithium and (-)-sparteine (3) at -78 °C (Scheme 4). The resultant isotactic polymer is optically active, and is postulated to adopt a right-handed helix as it departs from the polymerization site. This polymer has been particularly successful as a chiral stationary phase for the chromatographic resolution of atropisomers [8]. Many modifications of the or-ganolithium initiator/chiral ligand system have been explored. Recently, Okamo-to has applied enantiopure radical initiators for the enantioselective polymerization of bulky methacrylate monomers [45]. 

C. Enantioselective photocyclization of acrylamides catalyzed by chiral acids... 

Abstract Computational methods are an indispensible tool for the study of metal-organic reaction mechanisms. A particularly fruitful area is that of transition metal-catalyzed hydrogenations, including enantioselective versions that are extensively used at both the laboratory and the industrial scale. This review covers computational studies of rhodium-, ruthenium-, and iridium-catalyzed hydrogenation of enamides, acrylamides, carbonyls, and unactivated olefins. The evolution of the mechanistic models and the relationship of the computational studies to experimental studies are discussed. 

In 2009, Tanaka and co-workers achieved Rh-catalyzed highly enantioselective intermolecular hydroacylation reactions of aliphatic aldehydes 48 with 1,1-substituted acrylamides 49 by using a cationic Rh/QuinoxP complex as the catalyst (Scheme 8.24a). Unfortunately, the reaction of simple benzaldehyde with acrylamide 49a was sluggish and the enantioselectivity was moderate, but utilizing (i ,R)-Me-DuPhos as the ligand could improve both yield and enantioselectivity (Scheme 8.24b). When cyclopentene-substituted amide 49b was subjected to the standard reaction conditions, a thermodynamically stable hydroacylation product 50b was generated with excellent diastereoselectivity (>99 1 dr) and enantioselectivity (97% ee), although dramatically reduced reactivity was observed (5% yield) (Scheme 8.24c). This report represents the first example of an asymmetric hydroacylation reaction of a trisubstituted alkene. 

Tanaka and Shibata reported the intermolecular hydro acylation of 1,1-di-substituted alkenes (acrylamides) with aldehydes by using a Rh(I)//-Bu-QuinoxP complex as catalytic precursor. Good yields and outstanding enantioselectivities in 74 were found for many aliphatic aldehydes. In contrast, benzaldehyde reacted... 

Scheme 8.29 Rh-catalysed enantioselective hydroacylation of acrylamides 73 and ketones 75.

Masutomi, K., Sakiyama, N., Noguchi, K., Tanaka, K. (2012). Rhodium-catalyzed regio-, diastereo-, and enantioselective [2+2+2] cycloaddition of 1,6-enynes with acrylamides. Angewandte Chemie International Edition, 51, 13031-13035. 

Yamamoto and Narasaka reported another example of a catalytic enantioselective fiiran cycloaddition reaction [54]. Reaction of 3-methylthiofuran with acrylamide 79 in the presence of 10mol% of a chiral titanium catalyst at — 10°C... 

Besides a highly active nitrile hydratase employed in the industrial production of acrylamide and nicotinamide [7-10] and a nitrilase [14,20-22], R. rhodochrous J1 contains an amidase with a high (5)-specificity in the hydrolysis of 2-phenylpropionamide. The corresponding gene was cloned and overexpressed in E. coli [71,72]. The recombinant enzyme was used for the preparation of (5)-2-phenylpropionic acid with high enantiomeric purity (Fig. 24) but could not recognize the configuration of 2-chloropropionitrile presumably due to the requirement of a bulky moiety for enantioselectivity. 

Pseudomonas chloraphis B23, the nitrile hydratase of which was used as the second-generation biocatalyst for the industrial production of acrylamide [83], contains additionally an enantioselective amidase that was purified and characterized as a typical homodimer [84]. The amidase exhibited activity against a broad range of ahphatic and aromatic amides and exhibited enantioselectivity for several aromatic amides including 2-phenyl-propionamide (Fig. 24), phenylalanine amide, and 2-(4-chlorophenyl)-3-methylbutyramide (Fig. 29), but not for the amide of naproxen. The enzyme resembles in a number of characteristics other enantioselective amidases. 

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