Dithiane anions, addition reactions

Routes to benzo-fused derivatives of 1,4-dioxanes, 1,4-oxathianes and 1,4-dithianes make use of anions or dianions of the appropriate 1,2-disubstituted benzene. An alternative approach to the synthesis of 1,4-benzodioxanes involves Diels-Alder addition reactions of alkenes across the quinone function of 1,2-benzoquinones, e.g. (352) — (353). 

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. 

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... 

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) ... 

Anionic Additions to Aldehydes. The /dCa of trans-, >-dithiolane 1,3-dioxide has been determined by Bordwell and disclosed by Aggarwal to be 19.1, a surprisingly low value compared to Trans-1,3-dithiane 1,3-dioxide (24.9). While the deprotonation of 1,3-dithiolane and 1,3-dithiolane 1-oxide leads to unstable carbanions that cleave, the anion of Trans-1,3-dithiolane 1,3-dioxide has shown sufBcient stability to undergo addition reactions with aldehydes. Moreover, because of the Cj-symmetry incorporated into a five-membered ring, its potential to serve as a chiral acyl anion equivalent has been tested. 

Micalizio and coworker reported a three-component coupling sequence for the synthesis of substituted pyridines in 2012 [121]. The reaction proceeded through nucleophilic addition of a dithiane anion to an Q ,/3-unsaturated carbonyl followed by metallacycle-mediated union of the resulting allylic alcohol with preformed trimethylsilane-imines (generated in situ by the low temperature reaction of lithium hexamethyldi-silazide with an aldehyde) and Ag(I)- or Hg(II)-mediated ring closure. Good yields of substituted pyridines were isolated. 

Acylsilanes. The reaction of anion (1) with alkyl halides generates a functionalized dithiane which, when hydrolyzed under mild conditions, provides the corresponding acylsilane (eq 16). More highly substituted acylsilanes have been accessed by initial formation of the dithiane from the aldehyde, followed by deprotonation and silylation with TMSCl (eq 17). Acylsilanes have been used as sterically hindered aldehyde equivalents forre-giocontrol in addition reactions (eq 18) and also as precursors for silyl-substituted vinyl triflates (eq 19). ... 

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. ... 

A total synthesis of ( )-aromatin has utilized the lithium anion of the dithiane of (E)-2-methyl-2-butenal as a functional equivalent of the thermodynamic enolate of methyl ethyl ketone in an aprotic Michael addition (Scheme 189) (81JOC825). Reaction of the lithium anion (805) with 2-methyl-2-cyclopentenone followed by alkylation of the ketone enolate as its copper salt with allyl bromide delivered (807). Ozonolysis afforded a tricarbonyl which cyclized with alkali to the aldol product (808). Additional steps utilizing conventional chemistry converted (808) into ( )-aromatin (809). 

A large number of workers have examined the effects of temperature, solvent and reaction times on the ratio of the products of 1,4-addition versus 1,2-addition of dithiane and other a-thioalkyl carb-anions.34 Their results show that in general 1,2-addition is kinetically favored and therefore predominates at low temperatures and in less polar solvents,34 34 5 whereas 1,4-addition is thermodynamically favored... 

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