Hydrogenation under phase-transfer conditions

Electronegatively substituted acetylenes, such as dimethyl acetylenedicar-boxylate, do not react under normal conditions but will add the elements of hydrogen fluoride by reaction with fluoride ion (e g, CsF or tetraalkylammonium dihydrogen trifluoride) and a proton source under phase-transfer conditions [49, 50] (equation 8)... 

Epoxidation systems based on molybdenum and tungsten catalysts have been extensively studied for more than 40 years. The typical catalysts - MoVI-oxo or WVI-oxo species - do, however, behave rather differently, depending on whether anionic or neutral complexes are employed. Whereas the anionic catalysts, especially the use of tungstates under phase-transfer conditions, are able to activate aqueous hydrogen peroxide efficiently for the formation of epoxides, neutral molybdenum or tungsten complexes do react with hydrogen peroxide, but better selectivities are often achieved with organic hydroperoxides (e.g., TBHP) as terminal oxidants [44, 45],... 

Amides are very weak nucleophiles, far too weak to attack alkyl halides, so they must first be converted to their conjugate bases. By this method, unsubstituted amides can be converted to N-substituted, or N-substituted to N,N-disubstituted, amides. Esters of sulfuric or sulfonic acids can also be substrates. Tertiary substrates give elimination. O-Alkylation is at times a side reaction. Both amides and sulfonamides have been alkylated under phase-transfer conditions. Lactams can be alkylated using similar procedures. Ethyl pyroglutamate (5-carboethoxy 2-pyrrolidinone) and related lactams were converted to N-alkyl derivatives via treatment with NaH (short contact time) followed by addition of the halide. 2-Pyrrolidinone derivatives can be alkylated using a similar procedure. Lactams can be reductively alkylated using aldehydes under catalytic hydrogenation... 

This methodology provides a general synthesis of L-amino acids in 92-96% ee and in chemical yields of about 40-60%. Thus reaction of 3 (X = Br) with NaN3 under phase-transfer conditions provides 6, which is homologated to the 1-chloro-2-azidoboronate 7. This product is oxidized by sodium chlorite directly to an azido carboxylic acid (8). Hydrogenation of 8 provides L-amino acids (9). 

The hydration number (the number of water molecules intimately associated with the salt) of the quaternary ammonium salt is very dependent upon the anion. The change in the order of reactivity is thus believed to be due to the hydration of the anion the highly hydrated chloride and cyanide ions are less reactive than expected, and the poorly hydrated iodide fares better under phase transfer conditions than in homogeneous reactions. Methanol may specifically solvate the anions via hydrogen bonding, and this effect is responsible for the low reactivity of more polar nucleophiles in that solvent. 

Wacker oxidation of styrene has also been performed in [bmim][BF4] and [bmim][PF6], at 60 °C with H2O2 and PdCF as a catalyst [19]. This system gave yields of acetophenone as high as 92 % after 3 h. Hydrogen peroxide may also be used under phase transfer conditions for alkene bond cleavage, to produce adipic acid (an intermediate in the synthesis of nylon-6) from cyclohexene (Scheme 9.9). 

Diethyl 7V-(t-butoxycarbonyl)phosphoramidate 18 is obtained from diethyl phospho-ramidate by successive treatment with oxalyl chloride and t-butyl alcohol. It forms a stable non-hydroscopic sodium salt, which reacts with a variety of alkyl halides in benzene in the presence of tetrabutylammonium bromide under phase-transfer conditions to give the corresponding TV-alkyl derivatives. The latter are cleaved by hydrogen chloride in benzene to yield amine hydrochlorides (equation 16)48. 

CATALYTIC HYDROGENATION UNDER PHASE-TRANSFER CATALYTIC CONDITIONS... 

Reaction of the a-hydroxyketone (+)-1402 with hydroxylamine hydrochloride gave the oxime (—)-1407 in 95% yield. A bis-methylation of (—)-1407 under phase transfer conditions afforded the corresponding dimethyl derivative (—)-1408. Stereoselective hydrogenation of (—)-1408 using H2/Pt02 led to the amine... 

The hydrofluoride anion is also useful for substituting tertiary diazo groups by hydrogen fluoride under phase-transfer conditions, giving products 4. The reaction is less efficient on secondary diazo compounds.330... 

Special reagents introduced more recently allow significant improvements in hydrohalogenation of alkenes. HC1, HBr, and HI in aqueous-organic two-phase systems under phase-transfer conditions readily add to alkenes affording halides in nearly quantitative yields.123 Appropriately prepared silica and alumina have been found to mediate the addition of HC1, HBr, and HI to alkenes.124 The method is very convenient since it uses hydrogen halides prepared in situ 124 125... 

Amino acid synthesis (8, 389). Alkylation of the aldimine (1) from glycine ethyl ester and /j-chlorobenzaldehyde under phase-transfer conditions offers a general route to amino acids. Either liquid-liquid phase-transfer or solid-liquid phase-transfer catalytic conditions are satisfactory with active halides, but alkylation with allylic halides and less active alkyl halides is best effected under ion-pair extraction conditions (6,41), with 1 equiv. of tetra-n-butylammonium hydrogen sulfate (76-95% yields).1... 

Bortolini, O., Conte, V., Di Furia, F. and Modena, G. (1986) Metal catalysis in oxidation by peroxides. Part 25. Molybdenum- and tungsten-catalyzed oxidations of alcohols by diluted hydrogen peroxide under phase-transfer conditions. /. Org. Chem., 51, 2661. Barak, G. and Sasson, Y. (1989) Effect of phase-transfer catalysis on the selectivity of hydrogen peroxide oxidation of aniline. /. Org. Chem., 54, 3484. 

Benzosultams 450 undergo a tandem alkylation-sulfanylation on treatment with 4-bromobutyl thiocyanate under phase transfer conditions. Extrusion of SO2 occurs on thermolysis of the resulting spiro-tetrahydrothiopyranobenzo-sultams, generating an azaxylylene and thence 6-aryl-3,4-dihydro-2//-thiopyrans by a [l,5]-sigmatropic hydrogen shift (Scheme 155) <2005T8848>. 

Weak acid-base chiral complex formation represents hydrogen bond catalysis (see Chapter 9) and deprotonation followed by cation/anion association under homogeneous, and also under phase-transfer conditions (see Chapter 4) [14, 65],... 

Alkylation of (4) with ethyl bromo acetate was effected under phase-transfer conditions with powdered potassium hydroxide and tetrabutyl ammonium bromide in tetrahydrofuran to yield compound (5), and the azide function in (5) was then reduced by catalytic hydrogenation (over Pd/C) to give (6). The aminoester (6) was resolved into its enantiomers via... 

Recently, a number of v/c-diols have been efficiently cleaved employing a heteropolyacid/hydrogen peroxide system under phase-transfer conditions.173 The conversions of the substrates were 60-100% and selectivities to the carboxylic acids were 30-98%. 

Table 3.5 Oxidation of alcohols to the corresponding carbonyl compounds with hydrogen peroxide catalysed by Mo(VI) or W(VI) complexes under phase-transfer conditions at 70°C ...

Heteropolyacid species of tungsten and molybdenum in the presence of hydrogen peroxide have also been employed for alcohol oxidation, again under phase-transfer conditions (Figure 3.38).201... 

Ruthenium(III) chloride has been shown to be particularly effective with hydrogen peroxide for the oxidation of alcohols under phase-transfer conditions.204 Primary alcohols are converted to acids, allylic and secondary alcohols to ketones, and benzyl alcohols to either benzaldehydes or benzoic acids. 

Fig. 1.26 Catalytic oxidations with hydrogen peroxide under phase transfer conditions.

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