Lactols, reaction with

In the reaction with epoxides, y-hydroxysulfones are obtained278-280. For example, Kondo and coworkers279 synthesized various (5-lactols 226 by treating sulfone acetals 225 with terminal epoxides as shown below. Dilithiated phenylsulfonylmethylene reacted with haloepoxide and afforded 3-(phenylsulfonyl)cycloalkanols281. Treatment of y, 5-epoxysulfones 227 and 229 with n-butyllithium resulted in cyclization to form cyclopropane derivatives 228 and bicyclobutane 230, respectively282. 

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 ... 

Enantio-pure five-membered cyclic nitrones (154) and (155) were formed in a one-pot synthesis from the corresponding lactols (152) and (153) as the result of their reactions with unsubstituted hydroxylamine and by (a) subsequent treatment with MsCl and NaOH (Scheme 2.55) (310a) or by (b) subsequent treatment with TBDMSC1,12, TPP, imidazole, and tetrabutylammonium fluoride (TBAF) (310b). 

Carbohydrate lactones have been used as the carbonyl reagent in the Reformatsky reaction. Thus, 2,3 5,6-di-O-cyclohexylidene-D-mannono-1,4-lactone [44, obtained by oxidation of the mannofuranose derivative (49)] reacted with ethyl bromoacetate and zinc to give the protected 2-deoxy-3-octulosonic acid ethyl ester (45a) in 69% yield (50). Ketonic hydrolysis with potassium hydroxide in aqueous methanol, followed by acidification and heating, afforded the 1-deoxyheptulose derivative 45b. Similarly, starting from compound 44, the 1-C-substituted allyl and propar-gyl lactols were prepared on reaction with allyl or propaigyl bromides in the presence of zinc (51). 

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 ... 

Radical cyclization of polyfunctional 5-hexenyl halides mediated by Et2Zn and catalyzed by nickel or palladium salts has been demonstrated to produce stereoselectively polyfunctional 5-membered carbo- and heterocycles [56, 57]. Based on this strategy a formal synthesis of methylenolactocin (11) was achieved (Scheme 20). The acetal 130, readily being built up by asymmetric alkylation of aldehyde 127 followed by reaction with butyl vinyl ether and NBS, served as the key intermediate for the construction of the lactone ring. Nickel(II)-catalyzed carbometallation was initiated with diethylzinc to yield exclusively the frans-disubstituted lactol 132, which could be oxidized directly by air to 134. Final oxidation under more forcing conditions then yielded the lactone (-)-75 as a known intermediate in the synthesis of (-)-methylenolactocin (11) [47aj. 

Intermolecular reactions with O- and A-nucleophiles produce labile adducts of type 65 (equation 42). These adducts can be used for reversible generation of oxyiminium cations in situ. In contrast, reaction of hydroxylamines with S- or 8-lactols results in intramolecular additions of an oxygen nucleophilic group to intermediate oxyiminium cation, thus providing stable cyclic products. Reactions of this type have been extensively used for glycosidation of hydroxylamine derivatives such as 66 (equation 42), resulting in neoglycosides of type 67 . 

For preparative-type resolutions (chromatography or other separation techniques) it is of vital importance that the derivatives can be cleaved smoothly to avoid chemical and optical losses. In addition, it would be advantageous to recover the CDA (see Section 3.2.1.2.). The Noe lactol (Tabic 1, entry 55) fulfills such criteria almost perfectly during the course of reaction with chiral alcohols to form diastereomeric acetals220. 

Ring-chain tautomerism of intermediate lactols is also exploited in a conversion of Reformatsky adducts 87 into enamines 88 via mesylation followed by reaction with aliphatic amines in CH2C12 at room temperature and in the presence of molecular sieves... 

Medium-sized lactones A new method for synthesis of lactones that is particularly useful in the case of medium sized ones involves the hypoiodite reaction with a catacondensed lactol such as 1, which results in cleavage to the ten-membered isomeric iodo lactone 2. Phoracantholide I (3) is obtained on reductive removal of iodine. 

A naive look at the product suggests an oxidation to a ketone followed by a Baeyer-Villiger like reaction. The product is best explained by a fragmentation from an intermediate chromate ester, resulting on an aldehyde and a stabilized tertiary carbocation that is transformed into a tertiary alcohol by reaction with water. The hydroxyaldehyde so obtained may evolve to the final lactone either via a lactol or a hydroxyacid. 

Selenides are oxidized to selenoxides that normally suffer an in situ elimination.111 Amines are destroyed,112 although its protection as amides or carbamates prevents the reaction with Collins reagent. Lactols are very quickly oxidized to lactones,113 unless a very great steric hindrance is present.114 Tertiary lactols suffer oxidation via its opened hydroxyketone form.115 The oxidation of tertiary lactols may be slow, so that an alcohol can be selectively oxidized. 

Chlorophenyl)glutarate monoethyl ester 87 was reduced to hydroxy acid and subsequently cyclized to afford lactone 88. This was further submitted to reduction with diisobutylaluminium hydride to provide lactol followed by Homer-Emmons reaction, which resulted in the formation of hydroxy ester product 89 in good yield. The alcohol was protected as silyl ether and the double bond in 89 was reduced with magnesium powder in methanol to provide methyl ester 90. The hydrolysis to the acid and condensation of the acid chloride with Evans s chiral auxiliary provided product 91, which was further converted to titanium enolate on reaction with TiCI. This was submitted to enolate-imine condensation in the presence of amine to afford 92. The silylation of the 92 with N, O-bis(trimethylsilyl) acetamide followed by treatment with tetrabutylammonium fluoride resulted in cyclization to form the azetidin-2-one ring and subsequently hydrolysis provided 93. This product was converted to bromide analog, which on treatment with LDA underwent intramolecular cyclization to afford the cholesterol absorption inhibitor spiro-(3-lactam (+)-SCH 54016 94. 

Reaction of the lactol 1 with the isocyanate 2 in acetonitrile in the presence of 5 mol % of DBU resulted in a cascade of reactions and formation of a pentacyclic product A in 86% yield. Treatment of A with methoxide gave the highly functionalised octahydroacridine 3 in 90% yield. 

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