Enediols synthesis

It will be seen that the enediolic system can theoretically be written in the isomeric 2-keto (II) or 3-keto (III) forms and these in turn are seen to be derived from the 2-keto and the 3-keto acids IV and V, respectively (compare with benzoin which reacts with iodine in an analogous fashion to L-ascorbic acid). Consequently the synthesis of L-ascorbic acid and of its analogs has consisted in devising methods for the formation of 2-keto or 3-keto hydroxy acids followed by their enolization and lactonization. Four main methods are available for the synthesis of analogs of L-ascorbic acid containing the characteristic five-membered unsaturated enediolic ring. 

Metallic tin, Sn(0), is even more effectively employed. For example, in the presence of Sn(0), allyl bromide and a-halocarbonyl compounds afford nucleophilic organometallic species, which add to aldehydes in good yields to give homoallylic alcohols (12) and g-hydroxycarbonyl compounds (13,14) respectively. a-Diketones could be reduced by activated Sn(0), to give tin(II) enediolates which in turn undergo aldol reaction to form a,g-dihydroxyketones (15,16). This reaction was successfully applied to a stereoselective synthesis of methyl D-glucosaminate (17). 

The biosynthesis of 9-/ -D-arabinosyladenine (14), which inhibits the synthesis of DNA in viruses and various tumors,70 has been thoroughly studied by Farmer and coworkers.8 2 -Ketoadenosine 13 was postulated to be an intermediate of the biosynthesis (see Scheme 1). This 2 -ketonu-cleoside 13, formed by oxidation at C-2 of adenosine, should be epimer-ized to the 2, 3 -enediol nucleoside, which undergoes reduction70 to give 14. 

A reaction, that does not involve the enediol takes place on halogenation. Treatment of 138 with hydrogen bromide-acetic acid affords 5-0-acetyl-6-bromo-6-deoxy-L-ascorbic acid (166).360 Compound 166 was used for the synthesis of 6-substituted derivatives of 138, via the 5,6-anhydro derivative.361... 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

The parallel synthesis of an exhaustively stereodiversified library of r-l,5-enediols by silyl-tethered RCM has also been described <20010L2157>. 

The first multistep synthesis of this compound was described by Conia and cowork-ers o.55 condensation of bicyclopropyl diester 29 to the bis-TMS-enediol... 

Reaction with a-hydroxy epoxides. This regioselective reaction provides a key step in a synthesis of a unique furyl sesquiterpene, pleraplysillin-l (5), isolated from a marine sponge. Thus treatment of 1 with TifO-i-Pr), results in the enediol 2. which is converted... 

Scheme 32. Synthesis of the protected enediol 124 by Bradsher cycloaddition [94]...

An improved synthesis of 5-acetyl-2-methoxy-5-methyI-2,4-dioxo-l,3,2-dioxa-phospholan (8), starting from the oxyphosphorane (7), has been reported, as has one of the enediol cyclic phosphoryl chloride (9 R==C1) from (9 R=OMe) via the corresponding pyrophosphate by reaction with phosgene-pyridine (see Organophosphorus Chemistry , Vol. 8, p. 106). ... 

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