1.4- Oxathianes, synthesis

An unusual 1,4-oxathian synthesis, the formation of (174) in 12% yield, was observed in the phase-transfer-catalysed generation of dimethyloxosulphonium methylide and its reaction with benzaldehyde. A possible pathway to (174) involves protonation and dehydration of the initial ylide-benzaldehyde adduct to give (175). Ylide formation at a methyl... 

Solladie-Cavallo A, Balaz M, Salisova M, Suteu C, Nafie LA, Cao X, Freedman TB. A new chiral oxathiane synthesis, resolution and absolute configuration determination by vibrational circular dichroism. Tetrahedron Asymmetry 2001 12 2605-2611. 

Solladie-Cavallo has recently reported a two-step asymmetric synthesis of dis-ubstituted N-tosylaziridines from (R,R,R,Ss)-(-)-sulfonium salt 2 (derived from Eliel s oxathiane see Section 1.2.1.1) and N-tosyl imines with use of phosphazine base (EtP2) to generate the ylide (Scheme 1.42) [67], Although the diastereoselectiv-ity was highly substrate-dependent, the enantioselectivities obtained were very high (98.7-99.9%). The chiral auxiliary, although used in stoichiometric quantities, could be isolated and reused, but the practicality and scope of this procedure is limited by the use of the strong - as well as expensive and sensitive - phospha-zene base. 

The synthesis of the 2-acyloxathianes 3 makes use of the fact that for stereoelectronic reasons1, electrophilic attack on conformationally locked 2-lithiated oxathianes 1 leads exclusively to equatorially substituted products 2. A subsequent oxidation step completes the synthesis. 

The major drawback to using oxathianes 3 is that they are difficult to obtain in optically pure form because their synthesis includes a tedious racemate resolution. In order to circumvent this problem, oxathiane 11 was developed. Its synthesis starts with the readily available ( + )-10-camphorsulfonie acid (8)49. 

Using oxathiane 11, ( + )-(i )-2-methoxy-2-phenylpropanoic acid was obtained in 97% ee, however, the synthesis contains some inconvenient reaction steps. Thus, reduction of ( + )-10-camphorsulfonic acid (8) leads in low yield to a mixture of 10-mercaptoisoborneol (9 A) and 10-mercaptoborneol (9B) which must be separated by chromatography. The oxathiane 10 resists deprotonation with butyllithium and, therefore,, y -butyllithium had to be employed. Furthermore, after addition of methylmagnesium iodide, cleavage of the oxathiane moiety 12, with iodomethane did not proceed as well as with the simpler oxathianes 3. 

Oxathiane dioxides lithiated 641 synthesis of 638, 647 Oxathiane oxides, synthesis of 352 Oxathiolane oxides, synthesis of 241 Oxaziridines 72, 254, 826 as optically active oxidizing agents 291 Oxazolidinones 826 Oxazolines 619, 788... 

The radicals derived by hydrogen abstraction from 1,3-dithianes and 1,3-oxathianes undergo intramolecular addition to ot,P-unsaturated esters and hence facilitate the synthesis of cycloalkanones <96T9713>. 

This procedure represents the first reported synthesis of cis- and further reaction product, 4//-l,4-thiazine 1,1-dioxide. A derivative of the latter, 3,5-diphenyl-4//-l, 4-thiazine 1,1-dioxide,... 

Further, a 1,2-oxathiane 2,2-dioxide derivative was obtained as a by-product (15-25%) in the enantioselective synthesis of Oasomycin A <2007AG545> all efforts to suppress this side reaction were not successful, and the reaction products of the hexafluorobutadiene sulfotrioxidation (among the main products a 4,5-dihydro-l,2-oxathiin 2,2-dioxide derivative) were identified by F NMR spectroscopy <2007RJA424>. 

A [4-f2] cycloaddition was the key step in the synthesis of substituted dihydrothiopyrans from 2-alkenyl-l,3-oxathianes and an alkene. The reaction was mediated by a Lewis acid. It is assumed that the Lewis acid attacks the oxygen of the heterocycle which upon ring opening gives the highly reactive cationic heterodiene which reacts with alkenes to the thiopyrans in 31-88% yield (Scheme 75) <2000TL371>. 

Thietes, four-membered precursors for the synthesis of 1,3-dilhianes or 1,3-oxathianes, provide access to the target heterocycles by reacting with either carbon disulfide and Lil <2002IJB1234, 2003S340> or, when the ring system denoted in Scheme 110 is aromatic, with diethyl 2-oxomalonate via a [4-1-2] cycloaddition pathway <1998JHC1505>. 

Taking advantage of a tandem sulfoxide elimination-sulfenic acid addition approach to cyclic sulfoxides <1977J(P1)1574>, the synthesis of a number of novel 1,4-oxathiane oxides 229 and 230 based on the intramolecular addition of sulfenic acids to alkenes or alkynes tethered through an ether linkage has been reported (Equation 38) <20050BC404>. 

Synthesis of 2,3-dihydro-l,4-dithiin 11 was accomplished from l,3-dithiol-2-one 247 in the presence of dibro-moethane and potassium hydroxide <1998JOG3952>, while reaction of 2,3-dichloro-l,4-dioxane with powdered Zn in hexamethylphosphoramide (HMPA) was used for the synthesis of 1,4-dioxene 10 <1998JPP10067773>. To obtain substituted 1,4-oxathianes, the hydrogenation of the corresponding partially saturated compounds has been employed <2001J(P1)2604>. 

Oxathiane 2-oxides aie fonned by the oxidative ring expansion of 2-alkylthio-2-benzylthiolane 1-oxides brought about by [bis(trifluoroacetoxy)iodo]benzene. That the reaction is only successful with the (lR )-diastereoisomeis is attributed to chelation between the nucleophilic S and O atoms and the hypervalent iodine <99EJ0943>. A diazo-mediated thiolane ring expansion is the key step in a synthesis of the acenaphtho-[U-b][l,4]oxathiine system <99JCS(P2)755>. 

Routes to benzo-fused derivatives of 1,4-dioxanes, 1,4-oxathianes and 1,4-dithianes make use of anions or dianions of the appropriate 1,2-disubstituted benzene. An alternative approach to the synthesis of 1,4-benzodioxanes involves Diels-Alder addition reactions of alkenes across the quinone function of 1,2-benzoquinones, e.g. (352) — (353). 

An asymmetric synthesis of mevalolactone in over 87% e.e. employs a 1,3-oxathiane as the chiral auxiliary (81TL2859). The reagent (818), easily prepared from (+)-pulegone (81TL2855), was metallated with u-butyllithium and the anion reacted with acetaldehyde. Oxidation of the diastereomeric mixture of alcohols to the ketone (819) and reaction of... 

In the absence of seeding, crystallization may take several weeks. It is preferable to separate a small sample of the precursor thiomenthol from its stereoisomers by HPLC (3% ethyl acetate in hexane as eluant) and prepare a small amount of pure oxathiane from this material. Alternatively, a small amount of the product may be purified by GLC on a 5% FFAP column. The melting point of pure material is 37-38°C. The checkers, who did not have seeding crystals, found that the early crops of crystals melted when the flask was allowed to warm to ambient temperature. Consequently the cold supernatant liquid was withdrawn from the crystals with a Pasteur pipette while the flask was maintained at ca. 0°C (ice-water bath). The crystals were subsequently recrystallized several times in the same flask without filtration. By this technique, white crystals melting at 32-35°C were obtained this material is spectrally pure and suitable for asymmetric synthesis. The supernatant liquid was also concentrated, as the submitters described, to obtain additional crops using this technique. 

The impact of commercial yeast strains on wine fermentation leads to the formation of metabolites of yellow passion fruit (Passiflora edulis Sims) 2-methyl-4-propyl-l,3-oxathian 79 (10MI282,98JAFC1076,98MI53). This oxathian exists in four enantiomeric forms, 79a-d, and there are pronounced sensory differences between them (06CRV4099) for their enan-tioselective synthesis, cf. (84HCA947, 85LA1185). It should be mentioned that most of the aforementioned sulfur heterocycles are sold worldwide as fragrances and flavors. 

Murray, W.T., Kelly, J.W., and Evans, S.A., Jr., Synthesis of substituted 1,4-oxathianes, mechanistic details of diethoxytriphenylphosphorane — and triphenylphosphine/tetra-chloromethane — promoted cyclodehydrations and 13C NMR spectroscopy, J. Org. Chem., 52, 525, 1987. 

The aldol reaction of dithioester enethiolates has been used for the synthesis of dithiolactones [123], chiral substrates for the Claisen rearrangement [124, 125], and oxathianes [126]. Thioamide enethiolates may be employed in this reaction as well as shown with /Tthiolactams [26], or with a precursor of the antitumour agent vinblastine [127]. 

The methods of synthesis, the configurational and conformational aspects of the stereochemistry and the main spectral properties and reactions of 1,3-oxathiane derivatives were reviewed after submitting the manuscript (2003H1477). 

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