Lithium aluminum hydride lactones

Lithium aluminum hydride (LiAlH4) is the most powerful of the hydride reagents. It reduces acid chlorides, esters, lactones, acids, anhydrides, aldehydes, ketones and epoxides to alcohols amides, nitriles, imines and oximes to amines primary and secondary alkyl halides and toluenesulfonates to... 

Because direct glycosidation of 4 with phenols is not possible, indirect methods must be used for the preparation of aryl D-glucofuranosidurono-6,3-lactones (29). In addition, aryl 2,5-di-O-acetyl-D-glucofuranosidurono-6,3-lactones (30), obtained35-37 from the reaction of 1,2,5-tri-0-acetyl-D-glucofuranurono-6,3-lactones with phenols, can only be deacetylated by such multi-step procedures as (1) ammonolysis of 30 to afford aryl D-glucofuranosiduronamides (31), followed by amide hydrolysis and lactonization, 35,37 or (2) reduction of 30 with lithium aluminum hydride, and subsequent oxidation of the intermediate aryl D-glucofuranosides38 (32) (see Scheme 1). 

The importance of reactions with complex, metal hydrides in carbohydrate chemistry is well documented by a vast number of publications that deal mainly with reduction of carbonyl groups, N- and O-acyl functions, lactones, azides, and epoxides, as well as with reactions of sulfonic esters. With rare exceptions, lithium aluminum hydride and lithium, sodium, or potassium borohydride are the... 

Scheme 21 shows the synthesis of a dihydrofuran derivative 86. Synthesis of this compound was described by Nam et al. [68] utilizing a furanone compound 87 synthesized by Kim et al. [61] via a similar synthetic approach as described in Scheme 17. The lactone was reduced using lithium aluminum hydride to give the diol 88 and intramolecular etherification using the Mitsunobu reaction afforded the dihydrofuran 86 in moderate yield (47%).

Several total syntheses of antirhine (11) and 18,19-dihydroantirhine (14) have been developed during the last decade. Wenkert et al. (136) employed a facile route to ( )-18,19-dihydroantirhine, using lactone 196 as a key building block. Base-catalyzed condensation of methyl 4-methylnicotinate (193) with methyl oxalate, followed by hydrolysis, oxidative decarboxylation with alkaline hydrogen peroxide, and final esterification, resulted in methyl 4-(methoxycar-bonylmethyl)nicotinate (194). Condensation of 194 with acetaldehyde and subsequent reduction afforded nicotinic ester derivative 195, which was reduced with lithium aluminum hydride, and the diol product obtained was oxidized with manganese dioxide to yield the desired lactone 196. Alkylation of 196 with tryptophyl bromide (197) resulted in a pyridinium salt whose catalytic reduction... 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

The neutralization values were influenced by reduction with strong reducing agents, lithium aluminum hydride, sodium borohydride, and amalgamated zinc plus hydrochloric acid (35, 46). For the most part, the consumption of NajCOj and of NaOEt decreased in equivalent amounts. This is further confirmation of the assumption that lactones of the fluorescein type or of the lactol type are present. The reaction with sodium ethoxide was shown to be no true neutralization, that is, exchange of H+for Na+, at all, but an addition reaction w ith the formation of the sodium salt of a semi-acetal or ketal ... 

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]. 

Countless reductions of esters to alcohols have been accomplished using lithium aluminum hydride. One half of a mol of this hydride is needed for reduction of 1 mol of the ester. Ester or its solution in ether is added to a solution of lithium aluminum hydride in ether. The heat of reaction brings the mixture to boiling. The reaction mixture is decomposed by ice-water and acidified with mineral acid to dissolve lithium and aluminum salts. Less frequently sodium hydroxide is used for this purpose. Yields of alcohols are frequently quantitative [83,1059]. Lactones afford glycols (diols) [575]. 

Acid treatment of a 3 1 mixture of murrayafoline A (7) and koenoline (8) led to chrestifoline A (192) in 70% yield. Addition of murrayafoline A (7) to a mixture of 1057 and lithium aluminum hydride in ether and dichloromethane afforded bismurrayafoline-A (197) in 19% yield (662) (Scheme 5.166). In addition to the aforementioned methods, the same group also reported a stereoselective synthesis of axially chiral bis-carbazole alkaloids by application of their "lactone concept" (663) and a reductive biaryl coupling leading to 2,2 -bis-carbazoles (664). 

Enantioselective reduction of prostereogenic anhydrides la-g with 4 equivalents of chiral reducing reagent, obtained from lithium aluminum hydride, enantiomerically pure (M)-, 1 -bi-2-naph-thol and ethanol, provides easier access to chiral lactones as exemplified by 3a-g.10 la. Absolute configurations of lactones 3 are based on chemical correlation and the ee value for 3b is determined by HPLC on the chiral column Chiralcel OB-H (Daicel Chemical Industries, Ltd.)101b. 

Sasaki42 performed trcms-hydroxylation of trcm,y-2-hydroxy-3-pent-enoic acid (89) with 40% peroxyacetie acid, and obtained 5-deoxy-DL-arabinono-l,4-laetone (90) as the sole product. Jary and Kefurt41 repeated this experiment, and found that the reaction was not fully stereospeci-fie besides 90, 5-deoxy-DL-ribono- 1,4-lactone (91) was also formed. Reduction of the mixture of 90 and 91 with lithium aluminum hydride gave the corresponding 5-deoxy-DL-pentitols (92 and 93) in the ratio of 2.8 1. 

Lithium aluminum hydride in ether readily reduces /3-propiolactones to 1,3-diols in fair to good yield. A recent application of this reaction is with the y-bromo-/3-lactone in equation (61), in which reductive cleavage of the bromine atom occurred simultaneously (78CC961). 

A new synthesis of ( )-menthofuran (155) has been described which involves a three-step reaction sequence from the cyclohexanone (152) via direct C-alkylation with ethyl 2-iodopropionate to give (153) (Scheme 35). Hydrolysis of the diester (153) with hydrochloric acid afforded 3,6-dimethyl-2,4,5,6,7,7a-hexahydrobenzofuran-2-one (154). The final step in the sequence was the conversion of the a,/3-unsaturated y-lactone ring into the furan ring by reduction with lithium aluminum hydride and 2-propanol to afford (i)-menthofuran (155) in satisfactory yield (80JOC1517). 

The diversity of the products obtained by the three-component domino-Knoevenagel-hetero-Diels-Alder reaction can be further increased by a different work-up of the formed cycloadduct 141. Thus, hydrogenolytic removal of the Cbz-group in 141 led to 151 with a lactam and an aldehyde moiety by reaction of the formed secondary amine with the lactone moiety followed by elimination of benzyl alcohol. Reduction of 151 with lithium aluminum hydride gave benzoquinolizidine 152 (Scheme 5.30). Alkaloids of this type have so far not been found in nature, but it can be assumed that they might exist, since they could easily be formed from deacetylisopecoside 153, which is an intermediate in the biosynthesis of emetine 111. 

Step la Reduction of the lactone with lithium aluminum hydride LiAlH4 provides the diol. 

Further, acetic acid lip-hydroxy-3,18,20-trione-pregn-4-ene lip,18-lactone 17-oxoethyl ether has been converted to lip-hydroxy-18-one-pregn-4-ene lip,18-lactone-3,20-bis-ethylenketal 17-oxoethyl ether, which was reduced with lithium-aluminum hydride to 3,20-bis-ethylenketal aldosterone. Then by hydrolisation of 3,20-bis-ethylenketal aldosterone with FICI04 aldosterone can be obtained. 

To a solution of 4.2 g of lithium aluminum hydride in 420 ml of ether under a nitrogen atmosphere and cooled in a ice bath was added dropwise a solution of 99 g of tributyltin chloride in 210 ml of ether. The cooling bath was removed and stirring continued at ambient temperature for 1.5 hours. To the cooled solution was added 260 ml of water. The organic layer was washed with water and dried. This solution was added slowly at 15°C to a solution of (+)-2p,4p-dihydroxy-3a-iodo-5a-(methoxymethyl)cyclopentane-ip-acetic acid y-lactone 4-benzoate in 240 ml of benzene. Then the solution was evaporated and the product was stirred with water. Yield of (-)-3a,5a-dihydroxy-2p-(hydroxymethyl)cyclopentane-la-acetic acid y-lactone 3-benzoate 93%. 

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