Epoxide with dithiane

With Dithiane. Dithiane is one of the most popular functionalized carbanion used for the ring opening of epoxides. This reaction has been studied by different groups [31,56], The anion of bis(phenylthio)methane has been successfully used for the opening of epoxides derived from furanose [56]. This method is an excellent way to prepare formyl derivatives that are suitable for chain extension by olefination. Alternatively formyl derivatives can be reduced to hydroxymethyl derivatives. A recent application of epoxide 33... 

The preparation of the branched C-formyl furanoside derivatives by opening of an epoxide with phenylthiomethyl lithium or 2-lithio-l,3-dithiane has been described (Scheme 3). ... 

Regioselective opening of 2 ,3 -/yxo-epoxides with a lithiated dithian gave rise to branched structures of type (63, B=U or T) which could be converted (Scheme 9) into 3 -C-difluoromethyl compounds (64) and thence into analogues (65) with an additional fluorine atom at C-2 . 22 Alternatively, intermediates (63) could be used as precursors for 3 -C-hydroxymethyl systems (66), 23 and, by successive fluorination, fluoromethyl analogues of types (67) and (68) were obtained. 22 jn a synthesis of 3 -deoxy-3 -hydroxymethyl adenosine (69), the branched-chain sugar derivative (70),... 

The same Ru catalytic complex developed for asymmetric epoxidation with air proved to be active and also highly enantioselective towards asymmetric sulfoxidation. Among different solvents, ethyl acetate showed the best results with 5% mol of catalyst loading at 25°C in air and visible light irradiation over 24-48 h. The oxygen transfer does not occur in the absence of visible light and no over-oxidation of the sulfoxide was observed for a series of aryl methyl sulfides and two substituted 1,3-dithianes that were successfully oxidized with ee in the range 72-98% (Scheme 23.24). 

The syntheses of radicicol (3) are based on RCM of a diene-ene system, which avoids the problem of regioselectivity, compatibility with labile groups such as a vinyl epoxide, the dithiane protecting group, and the /Z selectivity [14]. In these... 

Scheme 8.31 Smith Ill s three- and multicomponent linchpin coupling of metalated silyl dithiane 109 with epoxides.

The multicomponent linchpin coupling of silyl dithianes with epoxides was very efficiently used to access both the AB and CD spiroketal fragments of spongistatin. 

Carbanions generated from 1,3-dithianes also react with epoxides to give the expected products. 

Cyelobutanone has been prepared by (1) reaction of diazomethane with ketene,4 (2) treatment of methylenecyclobutane with performic acid, followed by cleavage of the resulting glycol with lead tetraacetate,s (3) ozonolysis of methylenecyclobutane, (4) epoxidation of methylene-cyclopropane followed by acid-catalyzed ring expansion,7 and (5) oxidative cleavage of cyclobutane trimethylene thioketal, which in turn is prepared from 2-(co-chloropropyl)-l,3-dithiane.8... 

Assembling a five-component coupling product in a single operation further extended this methodology. Following alkylation of dithiane 78 with epoxide (—)79 (2.6 equivalent each) to generate the unrearranged alkoxy dithiane 80, sequential addition of HMPA and (—)-epichlorohydrin 81 (1 equivalent) furnished the bis(silyloxy dithiane) carbinols (- -)82 in 66% yield (equation 29) . ... 

Danishefsky s total synthesis of 317 and its chlorine free precursor monocillin I 316 features an RCM reaction with a substrate 310 that in addition to a dithiane protective group contains a vinyl epoxide and a diene moiety at... 

For the very first report of a C- to O-silyl rearrangement occurring after epoxide opening with 2-TMS-l,3-dithiane, see P. F. Jones, M. F. Lappert, A. C. Szary, Journal of the Chemical Society, Perkin Transactions l 1973, 2272... 

With Functionalized Carbanions. Other nucleophilic carbanions, such as lithio-dithiane or sodiomalonate or acetylene anion react easily with epoxides. 

As with epoxides, carbanions can add in a 1,4 fashion to enones or nitrosugars. Nitromethane anion has been used [64], Dithiane anion has been successfully used in the addition to nitroolefins [65] and to enones [66], Accordingly, C-5 branched-chain glucose derivatives 47 and 48 have been prepared from nitroolefin 46 (Scheme 20) [67,68], Sugar-derived enones have been also used as acceptors in free radical reactions to trap alkyl radicals as well as anomeric radicals (see Schemes 29 and 30). 

The dithiane derivative 60 (Scheme 14) is such a compound, it being made from 2,3 5,6-di-0-isopropylidene-D-mannose by treatment with 2-lithio-l,3-dithiane to give a heptose dithioacetal that was refunctionalized at C-2-C-3 by way of the C-l anion and then converted to the 6,7-epoxide following selective acid-catalyzed cleavage of the 6,7-acetal ring. Treated with n-butyllithium it gives, in 70% yield, the cyclized 61, which is efficiently convertible into validatol 62, a component of validamycin A, by desulfurization with Raney nickel and de-O-protection by use of boron tribromide in dichloromethane [31]. 

In a recent approach to the preparation of dihydro-3(2H)-furanones by chemists from Thailand it was shown that consecutive, one-pot conventional treatment of 1,3-dithiane in THF with equimolar n-butyllithium, an epoxide, n-butyllithium, an aldehyde or ketone and, finally, methanesulfonyl chloride gave a spirocyclic dithioacetal in good (ca. 70%) yield. Hydrolysis with HgO/HgCl2 gave the corresponding dihydrofuranone. 

The acidity difference of hydrogen atoms adjacent to divalent sulfur compared to oxygen stems from the greater polarizability of sulfur and the longer C-S-bond length d-orbitals are not involved. In most cases treatment of dithianes with w-BuLi at temperatures of -30 °C is sufficient for the preparation of the lithio-derivatives. With pKA values of approximately 30, lithiated dithianes can react with aldehydes or ketones, epoxides and acid derivatives, but also with alkyl halides without competing elimination reactions. 

Sunay, U. Fraser-Reid, B. Synthetic studies relating to the C1-C9 eastern" half of rosara-micin. Tetrahedron Lett. 1986, 27, 5335-5338. Smith, A. B. Pitram, S. M. Boldi, A. M. Gaunt, M. J. Sfouggatakis, C. Moser, W. H. Multicomponent linchpin couplings. Reaction of dithiane anions with terminal epoxides, epichlorohydrin, and vinyl epoxides efficient, rapid, and stereocontrolled assembly of advanced fragments for complex molecule synthesis./. Am. Chem. Soc. 2003, 125, 14435— 14445. 

Metalation of 2-substituted 1,3-dithianes.1 This combination (1 1) is more efficient than BuLi/TMEDA for this metalation at —78°. The active species may be BuNa. Moreover, the resulting anion undergoes facile reaction with various electrophiles, even epoxides. 

Let us turn now to the other coupling partner, aldehyde 58 it was synthesised by the pathway shown in Scheme 17.18. The first step was a Sharpless catalytic asymmetric epoxidation on ( )-crotyl alcohol with the oxidant derived from (—)-diethyl tartrate. An in situ derivatisation with r-butyldiphenylsilylchloride was then performed. The desired epoxide 59 was readily isolated in 76% overall yield after chromatography. Treatment of 59 with 2-lithio-l,3-dithiane in THF and 1,3-dimethyl-3,4,5,6-tetrahydro-2(l/7)-pyrimidinone (DMPU also known as N,N-... 

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