Hydroxymethyl lactones

This methodology was initially applied to a synthesis of (—)-alloyohimbane (82) (Scheme 3.13) (29). Readily available levoglucosenone (75), a product of cellulose pyrolysis, was the starting material. Diels-Alder reaction of 75 with 1,3-butadiene afforded adduct 76 which underwent Wolff-Kishner elimination and subsequent acylation to provide the bicyclic enol ether 77. Hydrolysis followed by oxidation and saponification afforded hydroxymethyl lactone 78 which was then condensed with tryptamine to yield the amide diol 79. Periodate cleavage of the diol was followed by conversion to chloride 80 which was cyclized to afford lactam 81. Subsequent Bischler-Napieralski cyclization followed by hydrogenation of the olefin moiety afforded the target ( )-alloyohimbane (82). 

Chiral Alcohols and Lactones. HLAT) has been widely used for stereoselective oxidations of a variety of prochiral diols to lactones on a preparative scale. In most cases pro-(3) hydroxyl is oxidized irrespective of the substituents. The method is apphcable among others to tit-1,2-bis(hydroxymethyl) derivatives of cyclopropane, cyclobutane, cyclohexane, and cyclohexene. Resulting y-lactones are isolated in 68—90% yields and of 100% (164,165). 

The reaction between the chiral furanones (/ )-/3-angelica lactone 129 (Z = H) and 5-hydroxymethyl-2(5//)-furanone 143 (Z = OH) with cyclopentadiene was... 

In contrast, (benzyloxymethoxymethyl)lithium underwent addition to the a,/(-unsaturated y-lactone in the nonchelated confonnation to give, after reductive desulfurization, a protected (S)-dihydro-4-(hydroxymethyl)-2(3/f)-furanone19. 

The nonaromatic lactones from cis-13, and trcyclohexaneacetic acid14 were important intermediates in the synthesis of indole alkaloids. 

CI8H21Br07S 5-0-(p-Bromophenylsulfonyl)-2,21-0-cyclohexylidene-3-deoxy-2-C-(hydroxymethyl)-D-erythro-pentono-1,4-lactone HCDBPL 30 454... 

The formyl group in orthoformylselenophenecarboxylic acids on reduction to an hydroxymethyl group undergoes ring closure to lactones.100 To obtain 2,4-disubstituted selenophenes, 4-bromo-2-formylselenophene was prepared by the swamping catalyst method.101 Selenopheno[2,3-b]thiophene derivatives may be prepared from compound 84.102 Another route to substituted... 

Cycloaddition of the nitrone 161 to the lactone 160 in boiling benzene for 6 h gave a 53 37 10 mixture of the three optically active adducts 162-164 in 66% combined yield (Scheme 9.50). Formation of the diastereoisomers 162-164 can be rationalized in terms of a highly preferred anti approach of the nitrone to the hydroxymethyl group in the transition state. The isomer ratio in the adducts was found to be dependent upon the solvent used in the reaction. Optimization of the reaction or the dia-stereoselectivity by Lewis acid catalysis failed. However, attempts to accelerate the cycloadditions by microwave irradiation, using 1,4-dioxane as the solvent, were successful and the reaction time decreased from hours to less than 10 min with only a... 

Deoxy-2-C- (hydroxymethyl) -2,21-0-i8opro-pylidene-D-eryihro-pentono- y-lactone... 

The structure of hamamelose as 2-C -(hydroxymethyl)-D-ribose has been established by the investigations of Freudenberg and of Schmidt. The studies of the latter author culminated in the chemical synthesis of the lactone which results from the oxidation of hamamelose. 

Finally, when L-sorbose (81) was treated with hydrogen cyanide, a branched-chain, sugar lactone was formed which was characterized by converting it into a diacetal.127 An X-ray structure determination of this material revealed it to be 2,21 5,6-di-0-isopropylidene-[2-C-(hy-droxymethyl)-L-gulono-l,4-lactone] (82). However, all subsequent efforts to prepare 82 resulted in the formation of 2,3 5,6-di-0-isopropyli-dene-2-C-(hydroxymethyl)-L-gulono-l,4-lactone (83). 

C13H20O7 2,21 5,6-Di-0-isopropylidene-[2-C-(hydroxymethyl)-L-gulono-1,4-lactone] (IPHMGL)84... 

The chirality of compound 16b was completely inverted, to give 2,3-0-cyclohexylidene-L-ribonolactone (19), by means of a procedure (28) that involves oxidation of the hydroxymethyl group of 16b by ruthenium te-traoxide, followed by reduction of the lactone group. The resulting intermediate 1,5-lactone (18) underwent isomerization (with cyclohexylidene migration) upon refluxing in xylene, in the presence of a catalytic amount of D-camphorsulfonic acid [in Ref. (28) the formulas for the series were erroneously depicted]. 

R,5S)-4-HYDR0XYMETHYL-(5-0-tert-BUTYLDIMETHYLSIL0XYMETHYL)FURAN-2(5H)-ONE D-erythro-PENTONIC ACID, 2.3-DIDE0XY-5-0-[(1,1-DIMETHYLETHYL)DIMETHYLSILYL]-3-HYDROXYMETHYL)-, y-LACTONE (164848-06-0), 75, 139... 

PHOTOINDUCED-ADDITION OF METHANOL TO (5S)-(5-0-tert-BUTYLDIMETHYLSILOXYMETHYL)FURAN-2(5H)-ONE (4R,5S)-4-HYDROXYMETHYL-(5-0-tert-BUTYLDIMETHYLSILOXYMETHYL)FURAN-2(5H)-ONE (2(5H)-Furanone, 5-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-, (S)-and D-erythro-Pentonic acid, 2,3-dideoxy-5-0-[(1,1-dimethylethyl)dimethylsilyl]-3-(hydroxymethyl)-, y-lactone)... 

The lactonization-elimination step was investigated independently with a broad array of A,A-disubstituted 2-(hydroxymethyl)benzamides. The rate of this reaction was highly sensitive to the nature of the /V-subslilucnls and to pH (minimum at pH 5 - 6). Above pH 6, general base catalysis occurred. 

In a multistep reaction sequence, A-Boc-L-allylglycine was converted into detoxinine 9 (84TL4133). Hydroxymethyl L-allylglycine was converted via a lactone into (-)-bulgenicine 10 (86TL6079). 

The hydroxymethyl and carboxyl group of Ser can participate in pyrazole-ring formation, as shown in the transformation of A -protected L-Ser with the Mitsunobu reagent into a /3-lactone which afforded the N-protected serine hydrazide upon treatment with methyl hydrazine. Cyclization to 25 was achieved by diisopropyl azodicarboxylate (DIAD) and TPP [90H(31)79]. 

ASYMMETRIC SYNTHESIS OF (M)-2-HYDROXYMETHYL-1-(2-HYDROXY-4,6-DIMETHYLPHENYL)NAPHTHALENE VIA A CONFIGURATIONALLY UNSTABLE BIARYL LACTONE... 

It is interesting that, apparently, cyanide ion does substitute75 mainly at C-3, the cyano group being hydrolyzed under the conditions of the reaction with assistance from the 5-hydroxymethyl group, to give the lactone 60. Here, the reaction may be rationalized if the initial addition of cyanide is reversible, C-3- substituted product being irreversibly removed by hydrolysis.75... 

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