Benzyl alcohol bond, carbon-oxygen

Styrene derivatives can be selectively converted to the corresponding benzyl alcohols by molecular oxygen in the presence of bis(dimethylglyoximato)chloro(pyridine)cobalt(III) and sodium tetrahydroborate (equation 242).559 A likely mechanism for this reaction involves insertion of the alkene into the cobalt-hydride bond, followed by 02 insertion into the cobalt-carbon bond, as in equation (11), and decomposition of the peroxide adduct (168) to the ketone, which is reduced to alcohol by NaBH4 (equation 243). 

Arguably the most challenging aspect for the preparation of 1 was construction of the unsymmetrically substituted sec-sec chiral bis(trifluoromethyl)benzylic ether functionality with careful control of the relative and absolute stereochemistry [21], The original chemistry route to ether intermediate 18 involved an unselective etherification of chiral alcohol 10 with racemic imidate 17 and separation of a nearly 1 1 mixture of diastereomers, as shown in Scheme 7.3. Carbon-oxygen single bond forming reactions leading directly to chiral acyclic sec-sec ethers are particularly rare since known reactions are typically nonstereospecific. While notable exceptions have surfaced [22], each method provides ethers with particular substitution patterns which are not broadly applicable. 

Oxidation of benzyl alcohol catalysed by chloroperoxidase exhibits a very high prochiral selectivity involving only the cleavage of the pro-S C-H bond. The reaction mechanism involved the transfer of a hydrogen atom to the ferryl oxygen of the iron-oxo complex. An a-hydroxy-carbon radical and the iron-hydroxy complex P-Fe -OH form. They may lead to the hydrated benzaldehyde or stepwise with the formation of the intermediate a-hydroxy cation. 

In general, the breaking of the carbon—oxygen bond appears difficult to achieve and needs activation by strongly polar groups. For these reasons, alcohol deprotection is carried out cathodically under the form of benzylic[91] and allylic [92] ethers as well as tosylates [91]. Thus, Torii [93] used the 4-nitrobenzyl group to protect alcohols. The deprotection was carried out in two steps (1) reduction of the nitrogroup of the amine and (2) oxidation of the amine at a platinum electrode (yield up to 93%). 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

Exposure of benzylic alcohols, ethers, or esters to hydrogen in the presence of metal catalysts results in rupture of the reactive benzylic carbon-oxygen bond. This transformation is an example of hydrogenolysis, cleavage of a o- bond by catalytically activated hydrogen. 

Because the hydrogenolysis of the phenylmethyl (benzyl) ether in the final step occurs under neutral conditions, the tertiary alcohol function survives untouched. A tertiary butyl ether would have been a worse choice as a protecting group, because cleavage of its carbon-oxygen bond would have required acid (Section 9-8), which may cause dehydration (Section 9-2). 

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