1.3- Dithiane, lithiated

Propenyl)-1,3-dithiane, after lithiation and addition of zinc chloride, reacts with ethyl 2-oxopropanoate to give preferentially the. vvn-adduct37, which is an intermediate in the synthesis of racemic /ra .s-tetrahydro-2,3-dimethyl-5-oxo-2-furancarboxylic acid. It is assumed, that the ethoxycarbonyl group is brought to a pseudoaxial position in the cyclic transition state by the chelating zinc cation. 

In one case, the addition of lithiated 1,3-dithiane to ( )-l-nitropropene gave an adduct in modest enantiomeric excess (43% ee). In an independent study chiral lithium [(S)-(l-(dimethylamino)-ethyl](methyl)phenylcupratc and lithium mcthoxy(methyl)eupratc were reacted with ( )-(2-ni-troethenyl)benzene to give adducts in 1-2% enantiomeric excess36. 

The addition of a lithiated dithiane to a chiral a,/J-unsaturated sulfone has been reported, however, the stereochemical outcome and the diastereoselectivity was not addressed20. The addition of (lithiomcthylsulfonyl)benzenc to a chiral y-alkoxy-a-trimethylsilyl-aj-unsaturated sulfone gave exclusively the, vr -adduct1 2 3 4 5 7 8 9 10 11 12. 

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... 

The described procedure has been widely used by Smith III and coworkers [250] in the efficient total synthesis of natural products containing extended 1,3-hydroxylated chains. This architecture is often found as a structural element in polyene macrolide antibiotics [251] such as mycotoxin A and B, dermostatin, and roxaticin. The Smith group used the above-mentioned approach (e. g., as five-component coupling) for the synthesis of the pseudo-C2-symmetric trisacetonide (+)-2-471 [252], which was employed by Schreiber and coworkers [253] within the synthesis of (+)-mycotoxin A (2-470a) (Scheme 2.108). Thus, lithiation of 2.5 equiv. dithiane 2-462b followed by treat-... 

Ogura and coworkers178,179 continued their study of the addition of lithiated heterocycles to 2,3 5,6-di-0-isopropylidene-L-gulono-l,4-lactone (50) and related compounds. In the case of the addition of lithiated 1,3-dithiane to 50, it was shown178 by X-ray crystal-structure analysis that l-(l,3-dithian-2-yl)-2,3 5,6-di-0-isopropylidene-/3-L-gulofuranose is R at the anomeric carbon atom. This demonstrates that the product of this reaction is, surprisingly, the more sterically hindered of the two products possible. This is the opposite of that predicted for addition of the lithiated dithiane from the less hindered side of 50 if no equilibration of the initial adduct is involved. 

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. ... 

The enantioselective lithiation of anisolechromium tricarbonyl was used by Schmalz and Schellhaas in a route towards the natural product (+)-ptilocaulin . In situ hthi-ation and silylation of 410 with ent-h M gave ewf-411 in an optimized 91% ee (reaction carried ont at — 100°C over 10 min, see Scheme 169). A second, substrate-directed lithiation with BuLi alone, formation of the copper derivative and a quench with crotyl bromide gave 420. The planar chirality and reactivity of the chromium complex was then exploited in a nucleophilic addition of dithiane, which generated ptilocaulin precnrsor 421 (Scheme 172). The stereochemistry of componnd 421 has also been used to direct dearomatizing additions, yielding other classes of enones. ... 

The lithiation of y-chloro acetal 175 with lithium and a catalytic amount of naphthalene (4%) allowed the preparation of the intermediate 176, which can be considered as a masked lithium homoenolate, and was used for the preparation of the hydroxy ketone 179 through the hydroxy acetal 177 and dithiane 178 using known chemistry (Scheme 62)" . 

Chlorinated ketals 221 were lithiated using a catalytic amount (8%) of naphthalene in THE at —78°C to generate the corresponding masked lithium 5-enolates 222, which upon treatment with different electrophiles in THE at temperatures ranging between —78 and 20 °C, and final hydrolysis with water, afforded protected functionalized ketals 223 (Scheme 76). The application of this methodology to the chlorinated dithiane 224, under the same reaction conditions, gave the intermediate 225 and finally products 226 (Scheme 76) -... 

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... 

Exclusive C-2 lithiation was also observed in the case of the 1-ben-zenesulfonyl-3-(l,3-dithian-2-yl) derivative, but when an excess of/j-BuLi was employed, in an attempt to promote deprotonation in the dithiane ring, ortho-lithiation of the phenyl substituent was observed forming instead (Scheme 18) (9IT79I1). 

Lithiation of 2-propenyl-l,3-dithiane generates an allylic anion which reacts with active ketones at the side-chain carbon. The reaction was highly diastereoselective (96 4) and the product was obtained in 85% yield (Equation 58) <1996JOC1473>. 

The lithiation of sterically fixed r/,v-4,6-dimethyl-1,3-dithiane gave the equatorial lithio compound 2-lithio-4,6-dimethyl-l,3-dithiane, since only equatorial products are obtained by reaction with electrophiles57. 

Dithioacetals (see also dithianes and dithiolanes) alkylation of 98 as acyl anion equivalents 75 carbanions of 87,97-102 cleavage of 14-18,98,102 desulfurization of 78 metal-catalysed coupling 127 reaction with Grignard reagents 127 reductive lithiation of 89 synthesis of 12-19,97-102 Dithioacids synthesis of 40... 

BuLi deprotonates the alcohol obtained in the first reaction and also lithiates the added dithiane 8... 

Nucleophilic attack of lithiated dithiane 8 on the lithium alkox-ide of 24 gives 1,3-diol 9. 

Fig. 52. Steric course of lithiation of conformationally locked 1,3-dithiane...

The Corey-Seebach Reaction (or Seebach Umpolung) uses lithiated 1,3-dithianes as nucleophilic acylating agents. 

The lithiated 1,3-dithiane can be viewed as an masked acyl anion that is able to react with various electrophiles. 

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. 

Carbon nucleophiles which do not readily trigger the rearrangement of epoxides include lithiated dithianes [295, 304], lithiated sulfones [238], lithiated diarylphos-phine oxides [240, 305], lithium enolates [306], and allylic organolithium or organo-magnesium compounds [298, 307-310] (Scheme4.67). 

The side chain at C-7 is introduced with high selectivity the aldehyde group, obtained by desilylation and Dess-Martin oxidation, reacts regioselectively with the lithiated dithiane 18, since attack at the keto group is sterically hindered. In addition, the CP skeleton shields one side of the aldehyde, so that the desired diastereomer 19 is obtained as major product in a ratio of 11 1. 

Thermolysis of 3-(ort o-anisoyl)-l-(l-piperidinyl)-3-cyclobutenes 807 in the presence of mesitylene affords angular-fused xanthones 809 via formation and ring closure of the intermediate 808 (Scheme 226) <1997TL3663>. Linear-fused xanthones 810 are prepared by nucleophilic addition of aryl and heteroaryl lithiates to dithiane protected benzopyrone-fused cyclobutenediones 811 followed by hydroysis of the dithiane protecting group (Scheme 227) <1996JA12473>. 

An anionic 1,4-migration from C to C was also observed during the lithiation of 2-trimethylsilyl-l,3-dithiane derivatives 221 (equation 144)354. 

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