Alcohols, general hydrogenolysis

The general intermediate 107 vide supm) was transformed into the corresponding pyrrolidine-enamine 121, which, when reacted with chloroacetonitrile, afforded the nitrile 122. Epoxide formation led to compound 123, which was reductively cleaved to the alcohol 124. Hydrogenolysis of 124 yielded the debenzylated compound 125 which was dibenzoylated to the Masamune intermediate 98 (Scheme 4). 

Aiyl esters, prepared from the phenol and an acid chloride or anhydride in the presence of base, are readily cleaved by saponification. In general they are more readily cleaved than the related esters of alcohols, thus allowing selective removal of phenolic esters. 9-Fluorenecarboxylates and 9-xanthenecarboxylates are also cleaved by photolysis. To permit selective removal, a number of carbonate esters have been investigated aryl benzyl carbonates can be cleaved by hydrogenolysis aryl 2,2,2-trichloroethyl carbonates, by Zn/THF-H20. 

This result stands in contrast to hydrogenation of 2-oximino-]-indanone (R = H), which stopped spontaneously at the 2-amino-1-indanol stage under similar conditions (43). This latter result accords with the general exp>erience in reduction of aromatic -oximino ketones (35,37 38,39,40). The amino function usually severely inhibits hydrogenolysis of the alcohol. 

Oxazines are prone to hydrogenolysis since the relatively weak N-O bond is easily cleaved. This reaction has often been employed for the transformation of this cycle (generally obtained from nitrones) into amino alcohols in a stereocontrolled manner. For example, reaction of 57 with hydrogen and palladium on charcoal as catalyst (Equation 1) furnished the expected substituted pyrrolidine 58 in moderate yields <2003EJ01153>. 

Benzylic alcohols were also converted to hydrocarbons by sodium borohy-dride [621], by chloroalane [622], by borane [623], by zinc [624], and by hy-driodic acid [225,625], generally in good to excellent yields. Hydrogenolysis of benzylic alcohols may be accompanied by dehydration (where feasible) [622],... 

Partial reduction of phenols affords mixtures of allylic and vinylic alcohols. From the generality derived for aliphatic systems, the most hydrogenolysis of this mixture is expected with platinum, palladium, and iridium catalysts, and much less with rhodium and ruthenium, an expectation substantiated in practice. For example, hydrogenation of resorcinol in neutral medium affords 20, 19, and 70% cyclohexanediol over palladium-, platinum-, and rhodium-on-carbon, respectively (29). Many examples attest to the value of rhodium and ruthenium at elevated pressure in avoiding hydrogenolysis. 

Carnahan et al. obtained good yields of alcohols and glycols by hydrogenation of lower mono- and dicarboxylic acids over ruthenium dioxide or Ru-C at 135-225°C and 34-69 MPa H2 (eqs. 10.1 and 10.2).8 In general, the optimum temperature was about 150°C. The chief side reaction was hydrogenolysis of the alcohols, as exemplified in the formation of ethanol from oxalic acid and of butanol and propanol from succinic acid (see eq. 10.2). Platinum and palladium catalysts were ineffective under similar or even more severe conditions. 

In order to study the hydrogenolysis in phenyl ether and its relationship to the formation of intermediates, Fukuchi and Nishimura hydrogenated phenyl ether and related compounds over unsupported ruthenium, rhodium, osmium, iridium, and platinum metals in f-butyl alcohol at 50°C and the atmospheric hydrogen pressure.151 The results are shown in Tables 11.11 and 11.12. In general, the greater part of the initial products as determined by an extrapolation method has been found to be cyclohexyl phenyl ether, phenol, and cyclohexane (Table 11.11). Over ruthenium, however, cyclohexanol was found in a greater amount than phenol even in the initial products. Small amounts of cyclohexyl ether, 1-cyclohexenyl cyclohexyl ether, cyclohexanol, cyclohexanone, and benzene were also formed simultaneously. 

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