Lactols from lactones

Reduction of lactones leads to cyclic bemiacetals of aldehydes. With a stoichiometric amount of lithium aluminum hydride in tetrahydrofuran at —10° to —15° and using the inverse technique, y-valerolactone was converted in 58% yield to 2-hydroxy-5-methyl tetrahydrofuran, and a-methyl-5-caprolac-tone in 64.5-84% yield to 3,6-dimethyl-2-hydroxytetrahydropyran [1028]. Also diisobutylaluminum hydride in tetrahydrofuran solutions at subzero temperatures afforded high yields of lactols from lactones [7024]. 

Lactols from lactones. Reduction of lactones by this reagent system at room... 

Diisobutijlaluminum hydride Lactols from lactones Stereospecific reduction... 

Bis-(3-methyL2-butgl)borane Lactols from lactones... 

Reduction of lactones to lactols with diisobutylaluminum hydride has become an important, high-yielding reaction in the wake of many syntheses of prostaglandins. First introduced in this role in 1969, ° DIB AH can give 98% yields of lactols from y-lactones by reaction at -60 C for 20 min in toluene. ... 

Unusual carbanions. Lithium homoenolates are formed from P-aryl-a,P-unsaturated ketones and esters. Their reaction with carbonyl compounds leads to y-lactols and lactones. Reductive dechlorination of a-chloroimines provides a-amino carbanions. Access to 1,2-amino alcohols is assured. 

Esters and lactones can be partially reduced with the participation of a single hydride. Starting from esters, aldehydes are formed via the corresponding hemiace-tals. Starting from lactones, the products are generally lactols (Figure 3.51). 

Oxidation Reactions. Hypoiodite intermediates may be generated from the reaction of simple alcohols with NIS. When conducted under photochemical irradiation, the products of Barton-type or fragmentation reactions of alkoxyl radical intermediates may be obtained. Aldehydes are oxidized to methyl esters via hemiacetal intermediates by reaction with NIS in methanol at rt. However, such conditions are not effective for the oxidation of simple alcohols. The combination of NIS and Tetrabutylammonium Iodide in dichloromethane has been developed for the oxidation of a variety of alcohols to the corresponding carbonyl corrpounds (eq 8). This reagent system is most widely used for the oxidation of lactols to lactones, in which near-quantitative yields are generally obtained under mild conditions (eq 9). ... 

The significant bias that IBX displays towards the relative rates of oxidation of primary and secondary alcohols may also be exploited in other ways. Despite the fact that in general, even mild oxidizing agents readily oxidize secondary lactols to lactones, IBX may be successfully employed in the previously unknown one-step synthesis of y-lactols from both 1,4-bis primary diols as well as from 1,4-primary-secondary diols. Treatment of a 1,4-diol with IBX in DMSO gives the desired y-lactol in good yield with very little over-oxidation to the corresponding lactone. Consequently this is an excellent procedure for the synthesis of y-lactols (eq 5)... 

Applications. Twelve examples are given in ref 2 to demonstrate the applications of fluorous sulfoxide 1 for the oxidation of primary alcohols to aldehydes (eq 2), secondary alcohols to ketones (eq 3), and lactols to lactones (eq 4). The mild reaction conditions and the tolerance of a broad range of functional groups, which are characteristic of the original Swem oxidation protocol, are retained. The reactions are generally completed in 2-3 h. The desired aldehydes, ketones, or lactones are Isolated in 84-90% yields, while fluorous sulfide 2 is separated from the reaction mixture by continuous extraction and is oxidized to sulfoxide 1 for reuse. 

Conjugate addition of methyl magnesium iodide in the presence of cuprous chloride to the enone (91) leads to the la-methyl product mesterolone (92) Although this is the thermodynamically unfavored axially disposed product, no possibility for isomerization exists in this case, since the ketone is once removed from this center. In an interesting synthesis of an oxa steroid, the enone (91) is first oxidized with lead tetraacetate the carbon at the 2 position is lost, affording the acid aldehyde. Reduction of this intermediate, also shown in the lactol form, with sodium borohydride affords the steroid lactone oxandrolone... 

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