Hydrogenolysis benzylic groups

A benzylidene acetal is a commonly used protective group for 1,2- and 1,3-diols. In the case of a 1,2,3-triol the 1,3-acetal is the preferred product. It has the advantage that it can be removed under neutral conditions by hydrogenolysis or by acid hydrolysis. Benzyl groups and isolated olefins have been hydrogenated in the presence of 1,3-benzylidene acetals. Benzylidene acetals of 1,2-diols are more susceptible to hydrogenolysis than are those of 1,3-diols. In fact, the former can be removed in the presence of the latter. A polymer-bound benzylidene acetal has also been prepared." ... 

Pd-C, EtOH, NaHC03, H2." Hydrogenolysis in the presence of NH4OAC cleaves only one benzyl group of a dibenzyl phosphate. ... 

The synthesis of the tranquilizer, spiropiperone (130) is completed by removal of the benzyl group by hydrogenolysis... 

The synthesis of a benzamide with a somewhat more complex side chain starts by condensation of acid 144 with racemic cis-aminopiperidine 152. Removal of the benzyl group of 153 by hydrogenolysis gives the secondary amine 154. Alkylation on nitrogen with the halide 155 gives finally the dopamine antagonist, cisapride (156) [38,39]. 

Nickel in the presence of ammonia is often used for reduction of nitriles to primary amines. The reaction is done at elevated temperatures and pressures ( 100 C, 1000 psig) unless massive amounts of nickel are used. Cobalt is used similarly but mainly under even more vigorous conditions. Nitriles containing a benzylamine can be reduced over Raney nickel to an amine without hydrogenolysis of the benzyl group (7). A solution of butoxycarbonyl)-3-aminopropyl]-N-<3-cyanopropyl)benzylamine (13.6 g) in 100 ml of ethanol containing 4 g. NaOH was reduced over 3.0 g Raney nickel at 40 psig for 28 h. The yield of A/ -benzyl-Air -(f-butoxycarbonyl)s >ermidine was 95% (7). 

Benzyl ester, hydrogenolysis of, 1034 Benzyl group, 518 Benzylic, 377... 

It is important to note that the one-step conversion of 27 to 28 (Scheme 4) not only facilitates purification, but also allows differentiation of the two carbonyl groups. After hydrogenolysis of the iV-benzyl group (see 28—>29), solvolysis of the -lactone-ring in 29 with benzyl alcohol and a catalytic amount of acetic acid at 70 °C provides a 3 1 equilibrium mixture of acyclic ester 30 and starting lactone 29. Compound 30 can be obtained in pure form simply by washing the solid mixture with isopropanol the material in the filtrate can be resubjected to the solvolysis reaction. 

The completion of the synthesis of gilvocarcin V (2) only requires a few functional group manipulations. Hydrogenolysis of the four benzyl groups, followed by acetylation of the liberated hydroxyl groups, provides 30 in 68 % overall yield. After cleavage of the MOM ether in 30 with bromotrimethylsilane, application... 

W. H. Hartung u. R. Simonoff, Hydrogenolysis of Benzyl Groups Attached to Oxygen, Nitrogen, or Sulfur, Organic Reactions, Vol.VII, S. 263—326, John Wiley Sons, London 1963. 

The benzyl group can serve as a hydroxy-protecting group if acidic conditions for ether cleavage cannot be tolerated. The benzyl C—O bond is cleaved by catalytic hydrogenolysis,176 or by electron-transfer reduction using sodium in liquid ammonia or... 

Hydrogenolysis of halides and benzylic groups presumably involves intermediates formed by oxidative addition to the active metal catalyst to generate intermediates similar to those involved in hydrogenation. The hydrogenolysis is completed by reductive elimination.58 Many other examples of this pattern of reactivity are discussed in Chapter 8. 

As seen in the retro-synthetic Scheme 5.3, intermediate 15 is useful for both routes. The choice of benzyl protection group was made based on the robust stability of benzyl phenol ethers toward most reactions and several possible avenues to remove it, although it was reported from Medicinal Chemistry that benzyl group removal via hydrogenolysis posed challenges in this compound. The choice of iodide substitution was born out of the known high reactivity of iodides in the Ullmann-type coupling reaction with alcohols and the robust stability of aryl iodides in many other common reactions. 

The deprotection of the Cbz protected amino acid proceeds via a two step mechanism (Figure 1). The first step comprises the catalytic hydrogenolysis of the benzyloxy group of the Cbz-protected amino acid (1). Toluene (3) is formed from the O-benzyl group as well as an unstable carbamic acid intermediate (2). This intermediate decomposes to form the unprotected amino acid (4) and carbon dioxide (5). 

Benzyl groups were removed from an acetyl-glucopyranoside over 5% Pd/C in EtOH-AcOH (5 1) under 50 psi H2 at room temperature.162 Hydrogenolysis of a hexapyranoside was made in EtOH-AcOH over 10% Pd/C under 55 psi hydrogen at room temperature for 21 days. The reaction time was shortened to 2 days by heating to 50°C.163 Benzyl-2,6-dideoxy- 3-D-glucopyranoside was... 

Concomitant hydrogenolysis of a benzyl ester and hydrogenation of a diene were performed in one step over Pt02 in AcOEt.207 In contrast, 10% Pd(OH)2/C in AcOEt or EtOH at room temperature for 1 hour under hydrogen was used for the hydrogenolysis of a benzyl group without the saturation of a cyclic carbon-carbon double bond.208... 

Hydrogenolysis of the benzyl group in a dioxane-containing compound under catalytic hydrogen-transfer conditions (10% Pd/C in MeOH and HC02NH4 for 10 minutes at room temperature) proceeded without affecting the dioxane moiety (Scheme 4.57).169,260... 

Desulfoxidation was achieved using Ra-Ni in ether. This was followed by selective hydrogenolysis of the benzyl group on W2 Ra-Ni under a hydrogen atmosphere in EtOH.420-422 Desulfoxidation had to be performed in ether use of ethanol as the solvent in desulfoxidation led to cleavage of a C-7-C-8 bond (Scheme 4.123). 

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