1.3- Dithiane 2-carbanion

The lone pair in the dithiane carbanion C can assume either an equatorial or axial position in the ring as shown below ... 

The widespread use of compounds derived from the 1,3-dithiane carbanion or its homologues as acyl anion equivalents (for applications see Section 4.2.1.1) followed the pioneering works of Corey and Seebach on nucleophilic acylation (for reviews, see [43] and [44]). 

In dithioacetals the proton geminal to the sulfur atoms can be abstracted at low temperature with bases such as Bu"Li. Lithium ion complexing bases such as DABCO, HMPA and TMEDA enhance the process. The resulting anion is a masked acyl carbanion, which enables an assortment of synthetic sequences to be realized via reaction with electrophiles. Thus, a dithioacetal derived from an aldehyde can be further functionalized at the aldehyde carbon with an alkyl halide, followed by thioacetal cleavage to produce a ketone. Dithiane carbanions allow the assemblage of polyfunctional systems in ways complementary to traditional synthetic routes. For instance, the p-hydtoxy ketone systems, conventionally obtained by an aldol process, can now be constructed from different sets of carbon groups. ... 

By treatment of the carbanion of (48) with an aldehyde, the procedure may be modified to yield hydroxy carbonyl compounds (51) (Scheme 25). Such dithian carbanions also react with epoxides e.g. (52), to give hydroxy ketones, e.g. (53). In this reaction, the less hindered end of the epoxide is preferentially attacked (Scheme 26). 

Veratraldehyde 3 and veratric acid methyl ester 4 were isolated from vanillic aldehyde 5 and vanillic acid methyl ester 6 in the original reaction mixture. Silica gel chromatography of this reaction mixture was used to isolate small amounts of these primary oxidation products. These compounds had lost two carbon atoms from the origind propenoidic chain. A further component isolated from the methylated mixture was 2-methoxyhomoveratric aldehyde 7, which suggested the presence of 2-hydroxyhomoveratric aldehyde 8 in the oxidation reaction mixture. Its structure was confirmed by independent synthesis. Treatment of the reaction mixture from the catalytic oxidation of E-ferulic acid 1 with 1,3-dithiane followed by methylation formed the thioketal 9, which was also prepared by reaction of veratraldehyde 3 with 1,3-dithiane carbanion 10 followed by methylation. 

The carbanions derived from thioacetals, however, are typical -synthons. Most frequently used are 1,3-dithianes and C -silylated thioethers (see p. 33f. D. Seebach, 1969, 1973 B.-T. Grobel, 1974,1977). In these derivatives the proton is removed by butyllithium in THF. 

The pA of 1,3-dithiane is 36.5 (Cs" ion pair in THF). The value for 2-phenyl-1,3-dithiane is 30.5. There are several factors which can contribute to the anion-stabilizing effect of sulfur substituents. Bond dipole effects contribute but carmot be the dominant factor because oxygen substituents do not have a comparable stabilizing effect. Polarizability of sulfur can also stabilize the carbanion. Delocalization can be described as involving 3d orbitals on sulfur or hyperconjugation with the a orbital of the C—S bond. MO calculations favor the latter interpretation. An experimental study of the rates of deprotonation of phenylthionitromethane indicates that sulfur polarizability is a major factor. Whatever the structural basis is, there is no question that thio substituents enhance... 

The pivotal step in this sequence is an electrophilic substitution on indole. Although the use of l,3-dithian-2-yl carbanions is well documented, it has been shown only recently that 1,3-dithian-2-yl carbenium ions can be used in a Priedel-Crafts type reaction. This was accomplished initially using 2-methoxy-l,3-dithiane [1,3-Dithiane, 2-methoxy-] or 2-metlioxy-l,3-dithiolane [1,3-Dithiolane, 2-methoxy-] and titanium tetrachloride [Titanate(l —), tetrachloro-] as the Lewis acid catalyst.9 2-Substituted lysergic acid derivatives and 3-substituted indoles have been prepared under these conditions, but the method is limited in scope by the difficulties of preparing substituted 2-methoxy-1,3-dithianes. l,3-Dithian-2-yl carbenium ions have also been prepared by protonation of ketene dithioacetals with trifluoroacetic acid,10 but this reaction cannot be used to introduce 1,3-dithiane moieties into indole. 

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

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

Pyridyl-l,3-dithianes (50) result from the reaction of picolyl lithium reagents with 1,2-dithiolanes in the presence of HMPT. An initial ring opening is followed by reaction at the carbanion site with a second mole of dithiolane <96PS(112)101>. 

Sulfur compounds are useful as nucleophilic acyl equivalents. The most common reagents of this type are 1,3-dithianes, which on lithiation provide a nucleophilic acyl equivalent. In dithianes an umpolung is achieved on the basis of the carbanion-stabilizing ability of the sulfur substituents. The lithio derivative is a reactive nucleophile toward alkyl halides and carbonyl compounds. 11... 

An example where the presence of a counterion makes a difference between the gas phase and solution phase pathways involves the intriguing carbanion produced on deprotonation of 1,3-dithiane at C-2. In solution, this species, almost invariably produced by reaction of the dithiane with butyllithium, is widely used as an acyl anion equivalent in synthetic chemistry. Its importance for the present work is that this is a configurationally stable lithiated species in solution the carbanion stays sp -hybridized, and the lithium prefers the equatorial position, even to the extent of driving a terr-butyl group on the same acidic C-2 carbanion to the axial position in the lithiocarbon species. The carbanion is thought to be stabilized primarily by orbital overlap with the C-S antibonding orbitals, as opposed to more conventional polar and 7t-resonance stabilization. ... 

Sulfonyl carbanions react readily with oxiranes, usually on the less hindered site With 2,3-disubstituted oxiranes, harsher conditions have to be used ° the addition of HMPA and/or BF3 Et20 can enhance the rate and the yield of the reaction, as in the case of lithiated dithianes. The reaction has been widely employed in organic... 

A 1,3-dithiane is a weak proton acid (pKa = 32) which can be deprotonated by strong bases such as n-butyllithium. The resulting carbanion is stabilized by the electron withdrawing effect of the two sulphur atoms. 

From the synthetic point of view, the most important a-sulfinyl carbanions appear to be those derived from dithioacetal S-oxides which are a synthon for acyl anions65. However, the yields of the alkylation reaction were found to be low. In spite of the fact that dithiane S-oxides have been intensively studied66 63, their synthetic applications are limited,... 

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