A-Alkylation reductive

Enders, D., Schubert, H. Enantioselective synthesis of P-substituted primary amines, a-alkylation/reductive amination of aldehydes via SAMP hydrazones. Arrgew. Chem., Int. Ed. Engl. 1984, 23, 365-366. 

Antistats such as polyoxyethylenes (151,152) and A/-alkyl polycarbonamide (153) are added to nylon to reduce static charge and improve moisture transport and soil release in fabrics. These additives also alter the luster of fiber spun from bright polymer. Static reduction in carpets is achieved primarily by the use of fibers modified with conductive carbon black (see Antistatic agents Carbon, carbon black). 

Several methods are available to supplement the phenol alkylations described above. Primary alkylphenols can be produced using the more traditional Friedel-Crafts reaction. Thus an -butylphenol can be synthesized direcdy from a butyl haUde, phenol, and mild Lewis acid catalyst. Alternatively, butyryl chloride can be used to acylate phenol producing a butyrophenone. Reduction with hydrazine (a Wolff-Kishner reduction) generates butylphenol. 

Reductive amination of cyclohexanone using primary and secondary aHphatic amines provides A/-alkylated cyclohexylamines. Dehydration to imine for the primary amines, to endocycHc enamine for the secondary amines is usually performed in situ prior to hydrogenation in batch processing. Alternatively, reduction of the /V-a1ky1ani1ines may be performed, as for /V,/V-dimethy1 cyclohexyl amine from /V, /V- di m e th y1 a n i1 i n e [121 -69-7] (12,13). One-step routes from phenol and the alkylamine (14) have also been practiced. 

A -Nitroso derivatives, prepared from secondary amines and nitrous acid, are cleaved by reduction (H2/Raney Ni, EtOH, 28°, 3.5 h CuCl/concd. HCF). Since many A -nitroso compounds are carcinogens, and because some racemiza-tion and cyclodehydration of A -nitroso derivatives of A -alkyl amino acids occur during peptide syntheses, A -nitroso derivatives are of limited value as protective groups. 

Coe et al. reported an efficient modification for the preparation of /-substituted indole analogs for biology screening in good yield. The intermediate P-nitrostyrene 44, prepared from the condensation of 43 with DMFDMA, underwent methanolysis and reduction to provide the aniline acetal intermediate 45. Alkylation of amine 45 was carried out employing standard conditions of reductive alkylation to provide A-alkyl analogs represented by 46. The indole 47 was generated by formation of the oxonium ion (from 46) under acidic conditions, followed by cyclization, accompanied by loss of methanol. 

In general, an ethyl(monoalkoxy)zinc is formed with amino alcohols6. Therefore, in the presence of an equimolar amount of chiral amino alcohol, a slow reduction of benzaldehyde to benzyl alcohol is observed rather than alkylation1. Alkylation only occurs with a ratio of diethylzinc to amino alcohol greater than equimolar. Consequently, a two-zinc species is postulated to be the actual catalyst1, n. 

The Reissert method15—conversion of an isoquinoline to a 2-benzoyl-1,2-dihydroisoquinaldonitrile (Reissert compound), alkylation, and hydrolysis—has enjoyed wide success in the synthesis of benzyliso-quinoline and related alkaloids.16,17 In particular, aporphines are prepared conveniently by converting isoquinolines to I-(o-nitrobcnzyl)-isoquinolines via a Reissert sequence, followed by A7-alkylation, reduction, and Pschorr cyclization.17... 

This procedure illustrates a general method for preparing aromatic hydrocarbons by the tandem alkylation-reduction of aromatic ketones and aldehydes.2 Additional examples are given in Table I. 

Reaction No. 5 (Table 11) is part of a synthetically useful method for the alkylation of aromatic compounds. At first the aromatic carboxylic acid is reductively alkylated by way of a Birch reduction in the presence of alkyl halides, this is then followed by an eliminative decarboxylation. In reaction No. 9 decarboxylation occurs probably by oxidation at the nitrogen to the radical cation that undergoes decarboxylation (see... 

Dynamic kinetic resolution of racemic ketones proceeds through asymmetric reduction when the substrate does racemize and the product does not under the applied experimental conditions. Dynamic kinetic resolution of a-alkyl P-keto ester has been performed through enzymatic reduction. One isomer, out of the four possible products for the unselective reduction (Figure 8.38), can be selectively synthesized using biocatalyst, and by changing the biocatalyst or conditions, all of the isomers can be selectively synthesized [29]. 

Dynamic kinetic resolution of a-alkyl-P-keto ester was conducted successfully using biocatalysts. For example, baker s yeast gave selectively syn(2R, 3S)-product [29a] and the selectivity was enhanced by using selective inhibitor [29b] or heat treatment of the yeast [29c]. Organic solvent was used for stereochemical control of G. candidum [29d]. Plant cell cultures were used for reduction of 2-methyl-3-oxobu-tanoate and afforded antialcohol with Marchantia [29e,f] and syn-isomer with Glycine max [29f]. 

White-rot fungus has been used as a biocatalyst for reduction and alkylation. The reaction of aromatic -keto nitriles with the white-rot fungus Curvularia lunata CECT 2130 in the presence of alcohols afforded alkylation-reduction reaction [291]. Alcohols such as ethanol, propanol, butanol, and isobutanol could be used (Figure 8.39d). 

Although the synthesis of multiple-pyrrolyl compounds can be achieved by SnAt reactions of perfluoroaromatics with pyrrolylsodium at ambient temperature <96JOC9012>, deleterious side reactions are often observed during attempted A-alkylations of the alkali salts of pyrrole. A protocol has therefore been developed for the preparation of N-arylmethylenepyrroles by reduction of the corresponding AT-acyl derivatives by treatment with sodium borohydride/boron trifluoride etherate in a sealed tube <96S457>. ... 

Electroreduction of the cationic Rh(IlI) complex [Rh(Por)(MeNFl2)2l in CH2CI2 followed by reaction with alkyl halides has been utilized to form a-alkyl products. The reaction scheme proposed for this reaction was one-electron reduction of Rh(lll) to form Rh(Por)-. This can either dimerize or attack the carbon atom of the alkyl halide RCH2X, the latter step involving elimination of either X- or 2t7.2.ix reactions of Co(ll) and Fe(II) porphyrins M(Por) with... 

During the course of the development of our group s alkylation/reductive decyanation strategy, a very reliable method for distinguishing between syn-and anfz-l,3-diols was discovered [17,18]. The acetonide methyl groups reliably display diagnostic C-NMR chemical shifts, allowing for stereochemistry to be determined simply by inspection (Fig. 1). Evans later extended the C-NMR chemical correlation to polypropionate chains [19,20]. 

Upon aluminum alkyl exposure the intensity of the EPR signals is reduced by 10-60% depending on the preparation condition. This can be interpreted as a further reduction of the Ti " centers in agreement with other experiments (see next section) however, the surface concentration of these sites varies considerably with preparation conditions. 

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