Synthetic applications benzylic alcohols

The only industrially important processes for the manufacturing of synthetic benzaldehyde involve the hydrolysis of benzal chloride [98-87-3] and the air oxidation of toluene. The hydrolysis of benzal chloride, which is produced by the side-chain chlorination of toluene, is the older of the two processes. It is no longer utilized in the United States. Other processes, including the oxidation of benzyl alcohol, the reduction of benzoyl chloride, and the reaction of carbon monoxide and benzene, have been utilized in the past, but they no longer have any industrial application. 

Naiki, M. Shirakawa, S. Kon-i, K. Kondo, Y. Maruoka, K. Tris(2,6-diphenylbenzyl)amine (TDA) and tris(2,6-diphenylbenzyl)phosphine with unique bowl-shaped structures synthetic application of functionalized TDA to chemo-selective silylation of benzylic alcohols. Tetrahedron Lett. 2001, 42, 5467-5471. 

The CBS reduction has been employed in numerous synthetic applications.16 The cetirizine hydrochloride 32 (Zyrtec) is an effective treatment as a second-generation histamine HI antagonist for a range of allergic diseases. Zyrtec is one of the leading antihistamine drugs, with sales of 1.3 billion in 2004 in the United States alone. Corey and Helal prepared a chiral benzylic alcohol intermediate 34 en route to their enantioselective synthesis of Zyrtec17 (Scheme 4.3m). The asymmetric reduction of the ketone 33 in toluene with catecholborane in... 

Few synthetically useful examples of the oxidation of ethers by oxygen or ozcne have been publish-ed. In 1978, Ourisson and coworkers reported that ozonization of the natural product cedrane oxide (43) on silica gel at -78 °C led to the formation of the corresponding lactone 44) in 30% yield (equation 32). A small amount of the tertiary alcohol (45) was also produced. Later, in the course of a chiral total synthesis of compactin, Hirama examined the ozonolysis of the alkene (46 equation 33). Under carefully controlled conditions, selective ozonolysis of the double bond could be achieved in 88% yield. However, when excess ozone was employed, significant amounts of the benzoate (47) were obtained, even at -78 C. In subsequent studies, benzyl ethers of primary and secondary alcohols, and carbohydrates were oxidized to the corresponding benzoates in excellent yields. Surprisingly, no further synthetic applications of this reaction have been reported. 

Although bidentate Lewis acids still remain poorly studied, it is increasingly difficult to dismiss them as esoteric reagents of mere academic interest because truly efficient and useful synthetic applications have recently appeared. The authors reported a new catalytic Meerwein-Ponndorf-Verley reduction [60,61 ] system based on the bidentate Lewis acid chemistry [62]. Treatment of benzaldehyde with (2,7-dimethyl-l,8-biphe-nylenedioxy)bis(diisopropoxyaluminum) (57) at room temperature instantaneously produced the reduced benzyl alcohol almost quantitatively (entry 2, Table 1-10). Moreover, even with 5 mol% of the catalyst 57 the reduction proceeds quite smoothly at room temperature to furnish benzyl alcohol in 81 % yield after 1 h (entry 3, Table 1-10). This remarkable efficiency can be ascribed to the double electrophilic activation of carbonyls by the bidentate aluminum catalyst (Scheme 1-21). 

Many other species are stabilized in 18-electron organometallic complexes car-benes and carbynes, enyls and polyenyls (XL ligands), o-xylylene (o-quinodime-thane), trimethylenemethane, benzyne, norbornadiene-7-one, cyclohexyne, 1,2-di-hydropyridines (intermediates in biological processes), thermodynamically unfavorable organic tautomers such as vinyl alcohols [less stable by 14 kcafrmol (58.5 kJ mol ) than their aldehyde tautomers], aromatic anions resulting from deprotonation in juxta-cyclic position such as tautomers of phenolates and benzylic carbanions. All these species have a specific reactivity that can lead to synthetic applications in the same way as cyclobutadiene above. 

The reactions of 2-lithio- and 2-sodio-imidazoles and -benzimidazoles are not particularly novel. The compounds do, however, prove a means of introducing a variety of functional groups into the 2-position of the heterocyclic ring. Such metalation reactions at C-2 can only occur readily when there is no alternative site for the metal. Therefore, only N-substituted imidazoles are of synthetic utility, and it may be necessary to select an N-substituent which can be removed later. For this reason, benzyl (removed by reductive or oxidative methods), benzenesulfonyl (removed by ammoniacal ethanol), trityl (hydrolyzed by mild acid treatment) and alkoxymethyl (easily hydrolyzed in acid or basic medium) groups have proved useful in this context. A typical reaction sequence is shown in Scheme 136 <78JOC438l, 77JHC517). In addition, reactions with aldehydes and ketones (to form alcohols), with ethyl formate (to form the alcohol) and with carbon dioxide (to form carboxylic acids) have found application (B-76MI40701). 

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