Reduction of lactones

MISCELLANEOUS BENZOHETEROCYCLES Partial reduction of lactone 166 (using for example diisobutylaluminum hydride in the cold) affords lactol 167. Condensation with nitromethane leads to the corresponding alkylated tetrahydrobenzopyran 170. The sequence probably starts by aldol reaction of the hydroxylactone form of the lactol (168) with nitrome thane to give the vinyl nitro intermediate 169 ... 

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]. 

A more useful way of reducing esters to ethers is a two-step procedure applied to the reduction of lactones to cyclic ethers. First the lactone is treated with diisobutylaluminum hydride in toluene at —78°, and the product - a lactol - is subjected to the action of triethylsilane and boron trifluoride etherate at —20° to —70°. y-Phenyl-y-butyrolactone was thus transformed to 2-phenyltetrahydrofuran in 75% yield, and 5-lactone of 3-methyl-5-phenyl-5-hydroxy-2-pentenoic acid to 4-methyl-2-phenyl-2,3-dihydropyran in 72% yield [1034]. 

Reduction of lactams (cyclic amines) 9-40 Reduction of lactones (cyclic ethers)... 

Lactones - ethers, y- and (5-Lactones can be converted into tetrahydrofuranes and tetrahydropyrancs, respectively, by a two-step procedure. The first step is the well-known reduction of lactones to lactols with DIBAH (1, 261 2, 140). The second step is deoxygenation of the alcohol with triethylsilanc and BF3 etherate.1 This reaction is compatible with several other functional groups, even including hydroxyl groups. 

Notes A reducing agent. Alcohols are generated from aldehydes, ketones, esters and acid chlorides. Nitriles can be converted to aldehydes. Tosylates will be replaced by -H halides are inert. Amides are reduced to amines. Reduction of lactones can provide a useful synthetic strategy ... 

In 1894, Fischer wrote "It will probably be possible to obtain all riiem-bers of the sugar group by a combination of the cyanohydrin reaction with the reduction of lactones, as soon as we have succeeded in finding the two optically active forms of glyceraldchyde. All observations agree with the isomerisms foreseen by Van t Hoff, above all the disappearance of isomers if the molecule becomes constitutionally symmetric. This includes the transformation of different stereoisomers into one and the same substance if one of several asymmetric centers is abolished." An example of this is... 

Reduction of lactone 5 results in lactol 6, a cyclic hemiacetal. Thus, the ester function is reduced only to the level of an aldehyde. 

The combination of polymethylhydrosiloxane (PMHS) and catalytic amounts of TBAF (1 mol%) and Cp2Ti(OC6H4Cl-4)2 (2 mol%) provides an efficient and convenient method for the partial reduction of lactones 187 to lactols 189 via hydrosilylation and subsequent hydrolysis of the resulting O-silyllactols 188 (equation 76)184. 

The chemoselective reduction of lactone 479 with LiBEt3H provided diol 480 with recovered starting material 479 (08T11580). 

The reduction of lactones, e.g., ribonolactone 537-540), can be carried out over a prolonged period with reasonable current efficiencies only at Hg cathodes ... 

A stable tetrahedral intermediate is more likely in the reduction of lactones, and DIBAL is most reliable in the reduction of lactones to lactols (cyclic hemiacetals), as in E.J. Corey s synthesis of the prostaglandins. The key step, the hydride transfer from Al, is shown in the green frame. 

DIBAL is also good for reducing nitriles to aldehydes. Indeed, this reaction and the reduction of lactones to lactols are the best things that DIBAL does. 

The asymmetric reduction of lactone (9) to give predominantly one atropoisomer can be achieved using 10 equiv of a complex prepared from LAH and BINAL (1 1) at —40°C. This reduction gives an 88 12ratio of (10a) (10b) in good yield (80%). Reduction of the same substrate with 8 equiv of a complex of LAH with (S)-(+)-2-(anilinomethyl)pyrrolidine in ether at —40°C leads to opposite stereochemical results (38 62 ratio of 10a 10b). 

Secondary or tertiary amides have been converted to aldehydes with Ph2SiH2 in the presence of Ti(0-f-Pr)4 (Eq. 133) [327]. It has been proposed that a species such as HTi(0-f-Pr)3 is the active reductant in this reaction. A similar reduction of lactones to lactols has also been reported [328]. 

Normally, lithium aluminum hydride is too vigorous a reagent for the reduction of lactones to the he-miacetal (hydroxyaldehyde lactol) stage, but, in certain circumstances under carefully controlled conditions, it can be used successfully. Usually, lactones give diols with LiAlH4 but, with 0.25 equiv., hemiacetals have been prepared from -y-lactones in high yield (Scheme Sodium bis(2-meth-... 

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. ... 

The reduction of lactones with DIBAL provides lactols. Lactols are latent hydroxy aldehydes. 

Diisobutylaluminum hydride (DIBAL) is a reliable reagent for the reduction of lactone 29 to the corresponding lactol 67. This is due to the formation of stable tetrahedral intermediate 66, which prevents further reduction (via hydroxyaldehyde 68 to the diol) and decomposes during aqueous workup to provide the desired lactol 67. 

The reduction of esters to aldehydes generally works best when alkoxy or amino functionality is in close proximity to the ester group, as in a- or -alkoxy esters. A neighboring alkoxy group will stabilize the tetrahedral intermediate through chelation and prevent overreduction. DIBAL-H-mediated mono-reduction of lactones delivers the corresponding lactols (hemiacetals). ... 

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

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