Epoxides reaction with dithiane anions

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). 

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. 

Protection of 194 as a p-methoxybenzylether and subsequent epoxydation led to the trans-epoxide 195, which was transformed into the unsaturated aldehyde 196 by a three-reaction sequence, including regioselective oxirane opening with a 1,3-dithiane anion, hydrolysis of the dithioacetal formed, and dehydration. Chlorite promoted aldehyde oxidation, methyl ester formation, and removal of the hydroxyl protections delivered methyl (+)-shikimate 197 in a remarkable 12% yield from 193. 

Multicomponent linchpin couplings can be carried out with 2-trialkylsilyl substituted 1,3-dithianes 207 and epoxides and was successfully used in the synthesis of natural products182. Tietze and coworkers303 found out that 2-lithio-2-trimethylsilyl-1,3-dithiane 208 reacted with two equivalents of a chiral epoxides in the presence of a crown ether to give first the monoadduct 209, which suffered 1,4-Brook rearrangement304 generating a new dithiane anion 210. Final reaction with an epoxide afforded products 211, which are equivalents of acetone aldol products (Scheme 60). 

What is more striking is how frequently such entities are generated by the application of two umpoled synthons double umpolung), such as in the reaction of a dithiane anion with an epoxide [85]. The advantage is clear if one of the functional groups must remain protected over many of the subsequent synthesis operations. In the case shown in Scheme 2.49, the keto function is converted into a dithiane at the outset, and therefore needs no extra protection step. 

The above two-step reaction sequence is of unusual interest from a synthetic perspective. Note that we have converted a typically electrophilic aldehyde (carbonyl) carbon into a nucleophilic carbanion center in the 1,3-dithiane anion. The overall process thus accomplishes a polarity inversion or, to use the more popular German term, umpolung. The 1,3-dithiane anion may now be reacted with a variety of electrophiles, such as alkyl halides, epoxides, and carbonyl compounds, in what is known as the Corey-Seebach reaction ... 

Multicomponent Linchpin Reactions. 2-Lithio-2-TMS-1,3-dithiane has also been employed as a bi-directional nucleophile or linchpin in epoxide opening reactions where both openings occur in an intermolecular fashion. The dithiane anion first attacks the less hindered carbon of the epoxide then, in the presence of THF and 12-crown-4,1,4-Brook rearrangement occurs with transfer of the TMS group to reveal a new dithiane anion that can react with an additional equivalent of epoxide (eq 27). This reaction, first reported by Tietze et al. in 1994, suffered from a lack of control over the rearrangement step, thus limiting the use to the formation of symmetric 1,5-diols. ... 

One of the most used sequential component reactions in the asymmetric construction of chiral compounds is the so-called anion relay chemistry (ARC) [2], This linchpin coupling protocol consists in the alkylation of an anion, generally a silyl lithium dithiane derivative, by an epoxide or an aziridine, resulting in an oxy- or aza-anion, which in the presence of hexamethylphosphoramide (HMPA) or other polar solvent gives a 1,4-Brook rearrangement, thereby leading to a new reactive dithiane anion that is capable of reacting with a second electrophile E+ (Scheme 11.1). 

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 successive reaction of (dibromomethyl)silanes with LDA (hthium diisopropyl-amide) and two equivalents of benzaldehyde gives 1,3-diol monosilyl ethers in good yield (Scheme 10.221) [574]. This tandem reaction would proceed via anionic 1,3-silyl migration of /l-lithioxyalkylsilane intermediate 152 and addition of the resulting lithium carbenoid to benzaldehyde. Thus, internal activation of the silicon-lithium alkoxide promotes nucleophilic addition of a-haloalkylsilanes. Similar tandem reactions of 2-trimethylsilyl-l,3-dithiane with aldehydes [575] and epoxides [576] have been reported. 

Attempts to effect the direct addition of 2-lithio-l,3-dithian to 17-keto-steroids have met with limited success. On the other hand, reactions of 17-spiro-epoxides were found to provide convenient access to homopregnane derivatives. Whereas treatment of the 17-ketoandrostene (188) with dimethylsulphoxonium methylide gave an inseparable mixture of the two epimers (189) and (190), reaction of (188) with dimethylsuphonium methylide afforded exclusively the 17j3-oxiran (189) in high yield. Opening of the epoxide of (189) with 2-methyl-1,3-dithianyl anion proceeded smoothly to give the 17)S-hydroxy-dithian (191). 

Although chlorohydrins are obtained in good yield and with high diastereoselectivity by the reaction of the anion derived from 2-chloro-1,3-dithiane 1,3-dioxide with aromatic aldehydes, subsequent ring closure to the epoxide is prevented by a competing retro-aldol reaction <97JCS(P1)11>. 

---