Reduction of lactone to lactol

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. 

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. 

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]. 

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. ... 

Cp2Ti(/>-ClC6H40)2 reacts with polymethyl hydroxiloxane to give an active center for the reduction of lactones to lactols.1910... 

Reduction of lactones to lactols. This reaction has generally been conducted with diisobutylaluminum hydride (1,261 2, 140). Japanese chemists effected... 

In some cases, it is possible to limit the reduction to a single oxidation stage (specifically, the ester aldehyde conversion).212 Ester 184 was reduced at -90°C to give aldehyde 185, in 89% yield as part of Mulzer s synthesis of tartrolon B. l Notice that the reaction was run at low temperature, which is usually required for reduction to the aldehyde rather than the alcohol. In many cases, however, significant amounts of alcohol are formed, even at low temperatures. A popular use of DIBAL-H is reduction of lactones to lactols. This reduction can be done to protect the lactone, as in the reduction of 186 to lactol 187, which was not isolated but reacted with BF3 and methanol to give methoxy derivative 188 in 94% overall yield, as part of the Hart et al. synthesis of (-i-)-himbeline.2l9... 

Boron-mediated asymmetric aldol condensation methodology developed by Evans [90] served as an inspiration for preparation of daunosamine starting from chiral oxazoUdinones. It appeared that the choice of chiral auxiUary is quite important for the stereochemical outcome of planned reactions [91]. A successful series of reactions started from N -succinoylation of (R)-3-(l-oxo-3-carbomethoxypropyl)-4-diphenylmethyl)oxazolidin-2-one as a novel chiral auxihary. The chain extension was achieved in aldol condensation with protected lactaldehyde and the key intermediate 132 was converted into the target aminosugar 135, via Curtius rearrangement of carboxyhc acid azide, and reduction of lactone to lactol, as depicted in Scheme 24 [58]. Unexpectedly, boron catalysts were rather ineffective in the aldol condensation step and had to be replaced with more reactive lithiiun enolates (which proved to be non-Evans syn selective). 

Two new reagents have been introduced for the reduction of lactones. A modification of Red-al by addition of one equivalent of ethanol provides a method for reduction of lactones to lactols, and the easily prepared iron carbonyl complex NaHFe2(CO)g is useful for the reduction of the olefinic bond in a)3-unsaturated lactones, as well as in unsaturated esters and amides. ... 

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