A-Hydroxylactones

The cyclic a-hydroxylactone, pantolactone, has been used extensively as a chiral auxiliary in D-A reactions.84 Reactions involving TiCl4 and SnCl4 occur through chelated TSs.85... 

Fluorine has also been introduced onto the E ring. For instance, both epimers of 20-fluorocamptothecin, where the fluorine atom replaces the 20-hydroxyl, have been prepared by total synthesis via stereoselective fluorination with DAST of the (K) and (S) a-hydroxylactone precursors (Figure 4.53). An asymmetric... 

Lactone formation on treatment of uneatumted acids with pwox acids ib not confined to the field of fatty acid chemistry. Howell m l Taylor obtained a hydroxylactone, for instance, on adding perfoi nm acid to the indene derivative shown in Eq. 1 106). An epoxide < assumed to constitute the intermediate stage of this transformation. 

Not only acids but also a-hydroxylactones (y- and S-) when submitted to the system DIB-iodine underwent oxidative decarboxylation, accompanied by -fragmentation. This reaction took place under non-photochemical conditions in various solvents, at 20-58°C. The substrates - mainly sugar derivatives - eventually yielded, after a mechanistically interesting route, j8-iodo or a,/ -unsaturated compounds. An example follows [71] ... 

As another example, Lubineau [572] has shown that well available glyoxylate cycloadds to several dienes such as cyclopentadiene, cyclohexadiene and iso-prene. The reaction of cyclopentadiene 9-14 and glyoxylic acid 9-15 in water at pH 0.9 is complete within 90 min at 40 °C to give the diastereomeric a-hydroxylactones 9-16 and 9-17 via a cycloadduct as the primary intermediate (Fig. 9-5). 

Hydrated ruthenium dioxide will act as a catalyst for the oxidation of primary allylic alcohols (equations 8 and 9) in an oxygen atmosphere (a trace of the antioxidant 2,6-di-r-butyl-4-methylphenol is required to prevent autoxidation of the aldehyde to the acid). The oxidation is not accompanied by any loss in double bond stereochemistry, secondary allylic alcohols are oxidized but at a decreased rate, and saturated alcohols are scarcely oxidized at all. However, a-hydroxy ketones and a-hydroxylactones will oxidize under forcing conditions, so there is clearly likely to some degree of substrate dependence. ... 

Dondoni and co-workers [197,198,199,200,201,202,203,204,205,206] have shown that homologation of a-hydroxycarbaldehydes and a-hydroxylactones can be achieved with high... 

Pracejus also studied the tandem nucleophilic addition/diastereoselective protonation of optically pure (S)-phenylethylamine on phenylmethylketene [11], With the aim of synthesizing amino acids and their derivatives, Calmes and coworkers reinvestigated the reaction of prochiral ketenes (generated in situ from acid chorides in the presence of a tertiary amine) with (R)-pantolactonc, an a-hydroxylactone [12], The authors have shown that the diastereoselectivity is dependent on the base used. Particularly, triethylamine and quinuclidine afforded complementary results and the diasteromeric ratios observed with quinuclidine suggest that the high stereoselections could be observed in nucleophilic additions to prochiral ketenes in the presence of cinchona alkaloids. 

We shall illustrate this with Prestwich s synthesis11 of the natural anti-cancer compound (—)-aplysistatin 69. This interesting compound with a seven-membered cyclic ether and a bromine atom proclaiming its marine origin is probably made in nature by a polyolefin cyclisation and that strategy was used in the synthesis. The alkene must be removed 70 before the cyclisation can be reversed. The stereochemistry of the extra centre in 70 is unimportant until the realisation that it can be made by alkylation of a hydroxylactone 71 whose stereochemistry must be anti. 

A soln. of phthalic anhydride and Na-trichloroacetate in anhydrous 1,2-di-methoxyethane refluxed 20 min. with stirring, more solvent added after thick paste has formed, heating continued 45 min., the resulting salt treated with water, filtered, and acidified with HGl 3-hydroxy-3-trichloromethylphthalide. Y 80%. F. e. and ring-chain tautomerism between a)-hydroxylactones and ketocarboxylic acids s. A. Winston et al., J. Org. Ghem. 30, 2784 (1965). 

Torri, C. Lesci, I.G. Fabbri, D. Analytical study on the production of a hydroxylactone from catalytic pyrolysis of carbohydrates with nanopowder aluminium titanate. J. Anal. Appl. Pyrol. 2009, 84, 25-30. 

The strategy being pursued is guided by knowledge obtained during the structure elucidation that the hemilactal component of (140) (Scheme 34) exists in equilibrium with a-hydroxylactone forms such as (141) 103). One mode of disconnection of the latter (Scheme 34) leads sequentially to the glyoxylate ester (142) and thence to the meso dialdehyde (143). Actually, employment of (143) would yield a racemic product unless the aldehydic centres were differentiated as in the case of dinitro equivalent... 

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