Aromatic esters, hydrogenolysis

With <, / -unsaturated aromatic esters, the aromatic nucleus seems to destabilize the alkylcobaltcarbonyl, thus favoring hydrogenolysis rather than CO insertion or isomerization. 

Fig (12) Transformation of keto ester (94) to (96) is described. Michael addition leads the formation of the adduct (97) which is subjected to cyclization, aromatization and hydrogenolysis to obtain the phenol (99). This on diazotization, methylation and reduction afforded the amino ether (100). Further diazotization, methanolysis and saponification produce ethyl (+)-camosic acid dimethylether (102). 

With the palladium black in dioxane, 2-benzoyloxy- and 2-(2-naphthoyloxy)pyridines underwent rapid hydrogenolysis to form toluene and 2-methylnaphthalene, respectively, with liberation of 2-hydroxypyridine, which was further hydrogenated to 2-piperidone. Similarly, 4-benzoyloxypyridine was readily hydrogenolyzed to give toluene and 4-hydroxypyridine, which was not hydrogenated further (Scheme 12.6). Cavallito and Haskell suggested that the unusual ease of hydrogenolysis was associated with the weakness of the aromatic ester bond.39... 

Alkylation of potassium enolates is not always fruitful, and so counterion exchange with lithium bromide prior to addition of the electrophile has been recommended. Reduction of aromatic esters instead of acids provides a number of potential advantages. The esters tend to be more soluble than carboxylate salts, hydrogenolysis of 2-alkoxy substituents does not appear to present the s me problem, and the products are more stable. This can be important when enol ether functions are generated, allowing the necessarily acidic work-up procedures for carboxylic acids to be avoided. Indeed, the hydrolysis of enol ether functions may be very slow in aqueous acid and is best achieved through catalysis by mercury(II) nitrate. ... 

Lactones (cyclic esters) are usually stable toward hydrogenolysis. However, the aromatic lactones contain benzylic C—O bonds and can be hydrogenolyzed. As an example, the hydrogenolysis of an aromatic lactone was performed over Ra-Ni in THF under 4 atm H2 pressure at 50°C for 30 hours.213... 

The platinum catalysts are universally used for hydrogenation of almost any type of compound at room temperature and atmospheric or slightly elevated pressures (1-4 atm). They are usually not used for hydrogenolysis of benzyl-type residues, and are completely ineffective in reductions of acids or esters to alcohols. At elevated pressures (70-210atm) platinum oxide converts aromatics to perhydroaromatics at room temperature very rapidly [5]. 

In contrast to phenolic hydroxyl, benzylic hydroxyl is replaced by hydrogen very easily. In catalytic hydrogenation of aromatic aldehydes, ketones, acids and esters it is sometimes difficult to prevent the easy hydrogenolysis of the benzylic alcohols which result from the reduction of the above functions. A catalyst suitable for preventing hydrogenolysis of benzylic hydroxyl is platinized charcoal [28], Other catalysts, especially palladium on charcoal [619], palladium hydride [619], nickel [43], Raney nickel [619] and copper chromite [620], promote hydrogenolysis. In the case of chiral alcohols such as 2-phenyl-2-butanol hydrogenolysis took place with inversion over platinum and palladium, and with retention over Raney nickel (optical purities 59-66%) [619]. 

Hydrogenolysis (23S) of perchloryl aromatic compounds yields ArH and not ArOH, thus confirming the presence of a —Cl bond. Another useful reaction of FCIO3 involves the replacement of the active hydrogens of methylene compounds by fluorine (145, 262, 284). A typical example is the fluorination of malonic esters ... 

Cycloamidation has been used extensively to prepare 17-membered cycloisodityrosines. The acyclic biaryl ether precursors were prepared by methods including the Ullmann reaction 2-5 and nucleophilic aromatic substitution (SNAr)J6 7 Since these methods have all been used intramolecularly in cyclization reactions, they will be discussed in Sections 9.5.3 and 9.5.4. Evans and co-workers employed the pentafluorophenyl ester method of macrolactamization 8] to prepare 11, an intermediate in their total synthesis of OF4949-III (7) (Scheme 2)J3 In this case, the acidic removal of a Boc group was employed to release the cyclization substrate, although hydrogenolysis of a Z group is also effective 3 ... 

The condensation of an aldehyde, benzyl carbamate, and triphenyl phosphite, first described by Oleksyszyn et al., 25,26 affords a direct route to a-aminoalkylphosphonates 4 that are conveniently protected for subsequent reactions (Scheme 4). Since dealkylation of the quaternary phosphonium intermediate 3 is not possible in this case, formation of the pen-tavalent product 4 presumably involves activation of the solvent and formation of phenyl acetate. This method is useful for the synthesis of aliphatic and aromatic amino acid analogues. However, monomers with more elaborate side chains are often incompatible with the reaction conditions. The free amine can be liberated by treatment with HBr/AcOH or by hydrogenolysis after removal of the phenyl esters. The phosphonate moiety can be manipulated by ready exchange of the phenyl esters in alkaline MeOH and activation as described in Section 10.10.2.1.1. Related condensations with other trivalent phosphite derivatives have been reported. 27-30 ... 

In Fig. (12) keto ester (94) was selected as starting material. It was converted to the formyl derivative (95) which yielded a,P-unsaturated aldehyde (96) by treatment with DDQ. Michael addition of the sodium enolate of tert-butyl- isovalerylacetate to aldehyde (96) afforded the adduct (97) as a mixture of C-ll diastereomers. By fractional crystallization one of the adducts could be separated but for the synthetic purpose the mixture was not separated. Treatment of the adduct (97) with p-toluenesulfonic acid in glacial acetic acid caused t-butyl ester cleavage, decarboxylation and cyclodehydration leading the formation of tricyclic enedione (98) in 80% yield. This approach was previously utilized by Meyer in the synthesis of nimbiol [29], Treatment of (98) with pyridinium bromide perbromide, followed by hydrogenolysis with palladium and carbon caused aromatization of (98) leading the formation of the phenolic ester (99). 

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