Dithiane anion addition

Michael addition of a dithiane anion 20, generated from the dithiane 19 with butyllithium, to the butenolide 21 creates the enolate 22 which has been efficiently alkylated in situ by 3,4,5-trimethoxybenzyl chloride to give 24 (mp 146-146.5 °C) in 65% overall yield. Protona-tion of 22 furnished the Michael adduct 23, which again can be deprotonated16 with LDA at — 78 °C to give 22 and alkylated (trimethoxybenzyl chloride, THF, HMPA, 3 h at — 78 °C, 18 h at 20 °C) to yield 24. Both variants are equally completely diastereoselective giving rise to the trans- product. 

The conjugate addition of aryl dithiane anions to 2-butenolide has been examined as a route to ( )-podorhizol and ( )-isopodophyllotoxone (78JOC985). The dithiane of piperonal (802) was deprotonated and reacted with 2-butenolide to give the lactone anion which was trapped in turn with 3,4,5-trimethoxybenzaldehyde to afford a mixture of the threo and erythro aldol products (803). Desulfurization of the erythro dithiane with Raney nickel gave ( )-podorhizol (804 Scheme 188). 

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). 

Stereoselective intramolecular conjugate addition reactions (Scheme 4) of dithiane anions tethered to an a,/ -unsaturated nitrile have been developed to advantage for the synthesis of axially substituted indolizidines and quinolizidines.81 The control of axial nitrile orientation by a peg-in-a-pocket template effect has been discussed. 

Dithiane anions undergo intramolecular conjugate addition to die a,/ -unsaturated nitrile moiety in (150) to produce indolizidine and quinolizidine (151), in which the nitrile group exhibits a strong, thermodynamic preference for die axial orientation.108... 

With the 1,4-dimethoxynaphthalene ligand, cyano-stabilized anions (including cyanohydrin acetal anions) and ester enolates equilibrate even at low temperature and strongly favor addition at the a-position (C-5). The kinetic site of addition is also generally C-a. However, the 2-lithio-l,3-dithiane anion and phenyllithium do not equilibrate over the temperature range -78 to 0°C. The sulfur-stabilized anions favor addition at C-/3 (equation 119) 134,190 phenyllithium... 

Stereoselective addition of a dithiane anion to chiral 2-methyl-3-trimethylsilyl-3-buterud combined with the stereoselective addition of a Grignard reagent to the chi a-alkoxy ketone affords a practical method for the construction of a,y-dimethyl-a,3-dihydroxy compounds, useful intermediates for the synthesis of erythronolides (Scheme 33). -Hydroxy cartmxylic esters were synthesized by the addition of ethyl l,3-dithiolanyl-2-carboxylate enolate to a chiral aldehyde, followed by desulfurization. ... 

Michael addition. ° The synthesis of the naturally occurring benz[a]anthraquinones, X-14881 (64 R = Me) and ochrotnycinone (R H) utilizes 2-phenyldithiane anion (Scheme 38), while 11-deoxydauno-mycinone was prepared using 2-methyldithiane. The formation of bicyclo[3.3.0]oct-l(5)-ene-2,6-dione utilizes 2-(2,2-diethoxyethyl)-l,3-dithiane anion. Conjugate addition of the highly stabilized anion (65) occurs readily with enamide (66), whereas the related acyclic anion (67) appears to be less reactive than the cyclic analog (Scheme 39). Conjugate addition of lithiated a-alkylthio monosulfoxide provides a new route for the synthesis of dihydrojasmone. ... 

Winterfeldf s synthesis of brefeldin A (Scheme 1.36) also entailed use of a Michael addition in an anti fashion to a 4-substituted cyclopentenone. Dithiane anion 217 was added in a 1,4 sense to enone 216 to give, after elimination of acetic acid, cyclopentenone 218. Addition of cuprate 219 to 218 in the expected anti manner cleanly afforded the trans cyclopentane 220. Hydride reduction gave the unnatural P-alcohol, which was inverted by a Mitsunobu reaction and the resulting ester cleaved to the desired a-alcohol 221. Protection of the alcohol... 

Examples taken from complete table ( 13), Ref. 1 activated anion = hetero-atom-stabilized carbanion, as Wittig reagent, nitroalkyl anion, dithiane anion, cyanide ion, etc. addition = carbonyl and related additions. 

Inversion of configuration (cf Epimerization) of alcohols (Mitsunobu reaction), 160-161, 286 of ally lie acetates with Pd, 27, 164 of allylpalladium with d-synthons, 27, 264 of alkyl halides or sulfonates by 1,3-dithiane anions, 22 by organylcuprates, 36 by tetracarbonylferrate<2 -X 46-47 in triorganylborane rearr., 37-38 of glycosides with free 2-OH by DAST, 272 of glycosyl halides, 271 of oxiranes by 1-alkync anions, 64, 204 by enolate type anions, 63-64 by internal alcoholate addition, 265 Inversion-esterification of alcohols, 160-161, 286 Inverted DNA , 345-346 Iodide, hydrogen porphyrin synthesis with, 255 Iodine = diiodine (Ij) ... 

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