Alcohols reductive alkylation

Et3SiH has been used to reduce p-trifluoromethylacetc henone to the alcohol, deoxygenate allyl alcohols, reductively alkylate enol esters using t-BuHgQ. ring open oxaziridines with enantioselective conversion to the silanol, while (H2CsCHSiMe2)2X cyclise to the disilacyclohexane and cyclopentane under radical conditions. ... 

Condensation of the anion obtained on reaction of acetonitrile with sodium amide, with o-chlorobenzophenone (36), affords the hydroxynitrile, 37. Catalytic reduction leads to the corresponding amino alcohol (note that the benzhydryl alcohol is not hydrogenolyzed). Reductive alkylation with formaldehyde and hydrogen in the presence of Raney nickel gives the antitussive a-gent, chlorphedianol (39). °... 

Alkylation lo yield a leriiary amine may occur easily if the formation involves cyclization (ii). Catalysts may have a marked influence. In reductive alkylation of ammonia wilh cyclohexanones, more primary amine was formed over Ru and Rh and more secondary amine over Pd and Pt. Reduction of the ketone to an alcohol is an important side reaction over ruthenium. 

Platinum and rhodium sulfided catalysts are very effective for reductive alkylation. They are more resistant to poisoning than are nonsulfided catalysts, have little tendency to reduce the carbonyl to an alcohol, and are effective for avoidance of dehydrohalogenation in reductive alkylation of chloronitroaromatics and chloroanilines (14,15). Sulfided catalysts are very much less active than nonsulfided and require, for economical use, elevated temperatures and pressures (300-2(KX) psig, 50-l80 C). Most industrial reductive alkylations, regardless of catalyst, are used at elevated temperatures and pressures to maximize space-time yields and for most economical use of catalysts. 

Reductive alkylation by alcohol solvents may occur as an unwanted side reaction 22,39), and it is to avoid this reaction that Freifelder (20) recom mends ruthenium instead of nickel in pyridine hydrogenation. Alkylation by alcohols may occur with surprising ease 67). Reduction of 18 in ethanol over 10% palladium-on carbon to an amino acid, followed bycyclization with /V,/V-dicyclohexylcarbodiimide gave a mixture of 19 and 20 wiih the major product being the /V-ethyl derivative 49,50). By carrying out the reduction in acetic acid, 20 was obtained as the sole cyclized product 40). 

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). 

The reduction of nitrobenzene to aniline is a major industrial process at the heart of the production of polyurethanes, and it is also often used as a marker reaction to compare activities of catalysts [1,2], It can be performed over a variety of catalysts and in a variety of solvents. As well as its main use in polymethanes, aniline is used in a wide range of industries such as dyes, agrochemicals, by further reaction and functionalisation. Reductive alkylation is one such way of functionalising aromatic amines [3, 4], The reaction usually takes place between an amine and a ketone, aldehyde or alcohol. However it is possible to reductively alkylate direct from the nitro precursor to the amine and in this way remove a processing step. In this study we examined the reductive alkylation of nitrobenzene and aniline by 1-hexanol. 

Ye et al. reported that the reduction of 2,4-dichlorophenyl-2-chloroethanone 1 with potassium borohydride in dimethylformamide to give 90% a-chloromethyl-2,4-dichlorobenzyl alcohol 2. Alkylation of imidazole with compound 2 in dimethyl formamide in the presence of sodium hydroxide and triethylbenzyl ammonium chloride, gave l-(2,4-dichlorophenyl-2-imidazolyl)ethanol 3 and etherification of 3 with 2,4-dichlorobenzyl chloride under the same condition, 62% yield of miconazole [9]. 

Tertiary Alkyl Alcohols. Tertiary alkyl alcohols generally undergo facile reduction when treated with acids in the presence of organosilicon hydrides.127,136 This comparative ease of reduction reflects the enhanced stability and ease of formation of tertiary alkyl carbenium ions compared with primary and secondary carbenium ions. Thus, treatment of 1-methylcyclohexanol with mixtures of triethylsilane and aluminum chloride in dichloromethane produces near quantitative yields of methylcyclohexane with or without added hydrogen chloride in as little as 30 minutes at room temperature, in contrast to the more vigorous conditions needed for the reduction of the secondary alcohol cyclohex-anol.136... 

Allyl halides, reduction reactions, 31 Aluminum chloride reagent/catalyst alkyl halide reduction, 30-31 secondary alkyl alcohol reduction, 14-15... 

Deuterium-labeled organosilicon hydride alkene to alkane reductions, 34 disubstituted alkenes, 37-38 alkyl halide reduction, 29-31 Diastereoselectivity, ketone-alcohol reduction, 76-79... 

S ilylation-intramolecular reduction, ketone-alcohol reduction, 78-79 Single-electron transfer (SET) process, alkyl halides and triflate reduction to alkanes, 28-31... 

Scheme 15 Cathodic Birch-type reduction of aliphatic esters to alcohols R alkyl, yields 95%.

Birch reduction-alkylation of 5 with 2-bromoethyl acetate was carried out with complete facial selectivity to give 57. This tetrafunctional intermediate was converted to the bicyclic iodolactone 58 ( > 99% ee) from which the radical cyclization substrate 59 was prepared. The key radical cyclization occurred with complete regio- and facial-selectivity and subsequent stereoselective reduction of the resulting tertiary radical gave 60 with the required trans BC ring fusion.The allylic alcohol rmit of (+)-lycorine was obtained by a photochemical radical decarboxylation, 62 63. 

---