Benzylic hydrogenation, with aldehydes

Prepare 3,5-dimethoxy benzyl alcohol by reducing the acid with lithium aluminum hydride as described elsewhere here, by hydrogenating the aldehyde (2-3 atmospheres H2, room temperature,Pt02 in ethanol - or by the NaBH4 method), in five steps as described in J ACS 70,666(1948), or prepare (II) directly by the doborane procedure. 

Nickel, Raney nickel and copper chromite are other catalysts suitable for hydrogenation of aldehydes to alcohols with little if any further hydrogenolysis. Benzaldehyde was hydrogenated to benzyl alcohol over nickel [43], Raney nickel [45] and copper chromite [50] in excellent yields. In the last-... 

This heme-dependent enzyme [EC 1.11.1.14], also known as diarylpropane peroxidase, diarylpropane oxygenase, and ligninase I, catalyzes the reaction of 1,2-bis(3,4-dimethoxyphenyl)propane-l,3-diol with hydrogen peroxide to produce veratraldehyde, l-(3,4-dimeth-ylphenyl)ethane-l,2-diol, and four water molecules. The enzyme brings about the oxidative cleavage of C—C bonds in a number of model compounds and also oxidizes benzyl alcohols to aldehydes or ketones. 

The N-alkylation of amines with alcohols [63] can also be carried out with Ir catalysts through a similar domino sequence reaction. In this case, the aldehyde/ketone resulting from oxidation is condensed with an amine to the corresponding imine, which is hydrogenated to the alkylated amine [63]. By way of example, the reaction of benzyl alcohol with aniline in toluene afforded benzylaniline in a 88% isolated yield by using catalytic amounts of [ lr(/z-Cl)Cp Cl 2]/K2C03. 

Methoxy-2-tetralone was methylated by the Stork method to yield 337. The latter was treated with sodium hydride and benzyl chloromethyl ether to furnish compound 338 in 60% yield. Ketalization of 338 afforded the ketal 339 which was hydrogenated with palladium on calcium carbonate to give the alcohol 340 in a yield of 92%. The alcohol 340 was oxidized with chromium trioxide in pyridine to afford the aldehyde 341 in quantitative... 

On this hypothesis, benzylic alcohols should exhibit the fastest reaction rates, owing to the higher stability of their corresponding carbocations. It is therefore apparent that the incomplete conversion observed under our experimental conditions is due not to an intrinsically poor reactivity of the substrates but to the inadequacy of styrene as hydrogen acceptor, unable to prevail over the aromatic aldehyde formed, highly activated toward hydrogenation with Cu/... 

A primary alcohol and amines can be used as an aldehyde precursor, because it can be oxidized by transfer hydrogenation. For example, the reaction of benzyl alcohol with excess olefin afforded the corresponding ketone in good yield in the presence of Rh complex and 2-amino-4-picoline [18]. Similarly, primary amines, which were transformed into imines by dehydrogenation, were also employed as a substrate instead of aldehydes [19]. Although various terminal olefins, alkynes [20], and even dienes [21] have been commonly used as a reaction partner in hydroiminoacylation reactions, internal olefins were ineffective. Recently, methyl sulfide-substituted aldehydes were successfully applied to the intermolecu-lar hydroacylation reaction [22], Also in the intramolecular hydroacylation, extension of substrates such as cyclopropane-substituted 4-enal [23], 4-alkynal [24], and 4,6-dienal [25] has been developed (Table 1). 

Treatment of N-acyloxazolidinones with di-n-butylboron triflate in the presence of Et3N furnishes the (Z)-(O) boron enolates. These on treatment with aldehydes give the corresponding 2,3-syn aldol products (the ratio of syn- to anti- isomers is typically 99 1 ). On hydrolysis they produce chiral a-methyl-(3-hydroxy carboxylic acids, as exemplified below. The facial selectivity of the chiral boron enolate is attributed to the favored rotomeric orientation of the oxazolidinone carbonyl group, where its dipole is opposed to the enolate oxygen dipole. At the Zimmerman-Traxler transition state, the aldehyde approaches the oxazolidinone appendage from the face of the hydrogen rather than from the benzyl substituent. 

Hydrogenolysis. A neat approach to syn-3-hydroxy a-amino acids involves condensation of (5)-5-phenylmorpholin-2-one with excess aldehyde, methanolysis, removal of the A-(hydroxymethyl)benzyl unit by hydrogenation with Pd(OH)/C and 1 equiv of CF3COOH, and saponification. The method can be used for access to polyoxamic acid. 

Recent developments tend to focus on the asymmetric aspects of stereoselective aldols but the diastereoselectivity is just as important. The cyclic ester 56 must of course form an E enolate and when the boron enolate -57 reacts with aldehydes the an//-aldol products 58 are formed with good stereoselectivity ranging from 4 1 to >20 1. The predominate isomer is that expected from the Zimmerman-Traxler transition state. The two benzylic-0 bonds can be cleaved by hydrogenation and the 2,3-dihydroxy acids anti-59 released in good yield.17... 

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