Dithioacetals deprotonation

The most systematically investigated acyl anion equivalents have been the IMS ethers of aromatic and heteroaromatic aldehyde cyanohydrins, TBDMS-protected cyanohydrins, - benzoyl-protected cyanohydrins, alkoxycaibonyl-protected cyanohydrins, THP-protected cyanohydrins, ethoxyethyl-protect cyanohydrins, a-(dialkylamino)nitriles, cyanophosphates, diethyl l-(trimethylsiloxy)-phenyimethyl phosphonate and dithioacetals. Deprotonation di these masked acyl anions under the action of strong basie, usually LDA, followed by treatment with a wide varies of electrophiles is of great synthetic value. If the electrophUe is another aldehyde, a-hydroxy ketones or benzoins are formed. More recently, the acyl caibanion equivalents formed by electroreduction of oxazolium salts were found to be useful for the formation of ketones, aldehydes or a-hydroxy ketones (Scheme 4). a-Methoxyvinyl-lithium also can act as an acyl anion equivalent and can be used for the formation of a-hydroxy ketones, a-diketones, ketones, y-diketones and silyl ketones. - - ... 

Treatment of selenoacetals 24 with butyllithium at 78 °C leads to the chiral a-seleno lithium compounds 25. Selenoacetals are stable compounds and can be readily prepared by selenoacetal-ization of the corresponding aldehydes25,26. In contrast to the corresponding dithioacetals, no competing deprotonation occurs on treatment with butyllithium, even with selenoacetals derived from aromatic aldehydes. 

As known from the Umpolung reactions, dithioacetals can be deprotonated efficiently among others [230, 306], a recent application is 122 [307] (Scheme 1.54). Even basic aluminum oxide can catalyze these isomerizations. One older example reports the isomerization of an S-propargyl phosphanesulfide to the allene [308],... 

The most popular method for generation of a-thio-carbanion (migration terminus) is direct lithiation (deprotonation) with alkyllithium or lithium amide. These deprotonation methods are widely applicable to various substrates, not only benzyl or allyl sulfides , but also dithioacetals 142 which form 143 (equation 83), and a phosphonate substituted system 144 which gives 145 (equation 84). ... 

If the reaction is carried out on dithioesters, carbanions stabilized by two a-sulfur atoms are formed. Such carbanions are analogous to those obtained by deprotonation of dithioacetals, such as Corey-Seebach... 

Metzner reports that lithium dithioenolates, which are softer nucleophiles than the corresponding carbonyl enolates, add kinetically in a 1,4-mode exclusively to ot, 3-enones and the diastereoselectivity preferences are similar to that for ester enolate additions.l43a d Typically, kinetic deprotonation of dithioesters affords predominantly the (Z)-enethiolate (170) which is opposite to that for esters 139 thus, with ( )-enones, anti adducts (172) are obtained. In contrast, the addition of methyl dithioacetate to ot,P-disubstituted enones affords predominantly syn adducts (174 and 175) which is a consequence of intramolecular protonation of the resultant enolate (Scheme 68).143e... 

The main class of electrophiles which reacts on the sulfur atom of enethiolates are alkyl halides. This was applied by Vallee and Tchertchian [121] in a one pot synthesis of hydroxy-ketenedithioacetals which elegantly uses the preceding features. Deprotonation of alkyl dithioacetates by LDA at -78 °C provided enethiolates which were treated by aldehydes. Comparable to the case of enolates, the aldol reaction takes place on the carbon atom. When water is added to the reaction mixture, 3-hydroxyalkanedithioates are obtained. However, if the quench is replaced by an alkyl halide addition, hydroxyketenedithioacetals are obtained. Formation of these compounds... 

Dithianes are extremely important compounds in organic synthesis because going from ketone to thioacetal inverts the polarity at the functionalized carbon atom. Aldehydes, as you are well aware, are electrophiles at the C=0 carbon atom, but dithioacetals, through deprotonation to an anion, are nucleophilic at this same atom. 

The protection of formaldehyde or other aldehydes as acyclic dithioacetals, sulfanylethers, sulfonylethers, thiosulfoxides, diselenoacetals, aminothioacetals and aminals, as well as cyclic dithioacetals, dioxolanes, oxazolidines and imidazolidines, allows the preparation of different type of protected acyllithium derivatives IV-XI by deprotonation (see... 

Successive double deprotonation-alkylation of the dithioacetal 150 has also been performed in a one-pot procedure159-161 and used in cyclization processes for the preparation of indoles160 and the phenanthrene nucleus161. The dialkylation has been performed with primary alkyl iodides and bromides without additives. The cyclic sulfate 153 has been acy-lated by means of compound 151 and, after further deprotection of the thioacetal moiety, transformed into the corresponding 2-deoxy-D-arabinohexopyranose 154 (Scheme 43)162. 

Intramolecular conjugate additions with nitriles 244 have been performed by deprotonation with n-BuLi in the presence of 12-crown-4 at room temperature, giving mainly indolizidine and quinolizidine derivatives 245 with the cyano group in an axial orientation (Scheme 67)395. The deprotection of the final dithioacetal has been achieved with bis(trifluoroacetoxy)iodobenzene396. 

Complex 100 (R = H) represents an organometallic equivalent of 1,3-dithiane. The rearrangement of carbanionic complexes, produced by deprotonation of 1,3-dithiane and other dithioacetals, and thioethers (110),... 

Mercaptalation of simple, organic, carbonyl compounds is considered24 to proceed by way of electrophilic addition of one thiol molecule, followed, for favorable examples, by bimolecular displacement of water from the protonated monothiohemiacetal intermediate, and, finally, deprotonation of the dithioacetal thus formed each step is presumed to be reversible, and Bethell and Ferrier25 demonstrated an example in which a diethyl dithioacetal reacted with ben-zenethiol in the presence of acid to form, in 80% yield, a diaster-eoisomeric mixture of ethyl phenyl dithioacetals. It is also known... 

Ketene dithioacetals are deprotonated with LDA-HMPA and complexed with copper(l) iodide (Scheme 36). This reagent reacts with allylic halides exclusively at the y-position with allylic rearrangement (5n20. The reaction of the lithium reagent with simple alkylating reagents gives mostly a-attack. Ketene dithioacetals can be converted to esters by aqueous mercury(II) chloride. 

Full details have been published of the synthesis of pyridines derived from the 1,5-dicarbonyl compounds resulting from the reaction of -ketoketene dithioacetals with the carbanions obtained by deprotonation of methyl ketones. 5 There have been two reports of the synthesis of pyridines from enamines and malononitrile.26,27 This route is exemplified by the conversion of the readily available enamines (10 Z=0 or S) into the 2-araino-3-cyanopyridines (11) ... 

It is quite interesting that the aromatic aldehyde derived dithioacetal 67 shows different anodic behavior from that of the aliphatic aldehyde derived dithioacetal 70. This can be explained by the pathway shown in Scheme 51. Deprotonation of the cation radical P arising from the aromatic dithioacetal 67 should be more facile than that from P which comes from the alkyl dithioacetal 70 as the former contains more acidic a-hydrogens. 

Reaction of the anion (243) with trimethylsilyl chloride, D2O and benzophenone, respectively, gave compounds (245), (246), and (247). Acid-treatment of (247) afforded ring-enlarged heterocycle (249) rather than the ketene dithioacetal (248), but (248) could he obtained by deprotonation of the trimethylsilyl derivative (245) with butyllithium and reaction with benzophenone <76TL1251>. 

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