Primary alcohols, ring-opening

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

We saw an example of nucleophilic ring opening of epoxides in Section 15 4 where the reaction of Grignard reagents with ethylene oxide was described as a synthetic route to primary alcohols... 

The reactivity of hydrido(ethoxo) complex 4 was examined (Scheme 6-15) [8]. Metatheses similar to those postulated for alcohol exchange (Eq. 6.5) occurred between HCl, LiCl, phenyl acetate or primary amines and yielded complexes 94. The reaction of 4 with cyclic anhydrides proceeded similarly to give iridium-assisted ring opening products 95. Heterocumulenes afforded the inserhon products 96 into the Ir-O bond. 

In the cases of oxiranes, the formation of alcohols and oxo compounds (ketones and aldehydes) are the result of primary processes.3,274-286 Hydrogenation of oxo compounds does not occur on surfaces covered with oxirane. The adsorption of oxiranes on metal surfaces is irreversible during adsorption, ring-opening takes place also. As the temperature is raised, the proportions of the oxo compounds increase. 

Ti(OPr1)4-mediated nucleophilic ring opening of 2,3-epoxy-alcohol with primary amine requires more rigorous conditions, and the product is a complex mixture. Lin and Zeng22 found that this problem could be overcome and moderate to good yields could be obtained under weak base conditions by in situ /V-acylation of the aminolysis product with benzoyl chloride. 

In animals, ascorbic acid is synthesized in the liver from o-glucose, by a pathway that initially involves specific enzymic oxidation of the primary alcohol function, giving o-glucuronic acid (see Section 12.8). This is followed by reduction to L-gulonic acid, which is effectively reduction of the carbonyl function in the ring-opened hemiacetal. 

In 1993, Yoshida et al. pubhshed trapoxin (TPX, Fig. 3), a fimgal product, which, in contrast to TSA, is an irreversible inhibitor of mammalian histone deacetylase [38]. When the epoxide moiety is reduced to the corresponding primary alcohol, HDAC inhibiting activity is completely lost. This observation emphasizes the importance of the oxirane ring, which most likely binds irreversibly via ring opening at the activated 2-position to a nucleophihc active site residue. 

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