Dithiane anion

In Step C a dithiane anion was used as a nucleophilic acyl anion equivalent to introduce the C(10)-C(13) isobutyl group. 

An abnormal (tele) substitution of chlorine in both 2,3- and 2,6-dichloropyrazines 91, 92 occurred on reaction with dithiane anion, while morpholine gave the normal //wo-substitution <06TL31>. Another paper described the highly selective ipso monosubstitution of the 2,3-dichloro compound by enolates in toluene <06T9919>. 

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). 

An important example of indirect substitution utilizes alkoxy leaving groups the intermediate (28) from the reaction of the [(diphenyl ether)Cr(CO)3] complex and the 2-methyl-1,3-dithiane anion can be induced to eliminate phenol by protonation at low temperature the result is tele substitution (equation 17). 

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... 

Heteroatom Stabilized Anions (Dithiane anion is an example) Sulfones... 

Dicyanopyridazine may react with pyrrole and indole systems as a heterocyclic azadiene in IEDDA Diels-Alder reactions. However, in acetic acid as solvent reaction occurs by substitution of CN at the 4-position and intermediates such as (10) may be isolated.50 Reaction of dichloropyrazines with a dithiane anion in THF may result in a tele-substitution process, as shown in Scheme 5, in which initial nucleophilic attack occurs at an unsubstituted ring position. Deprotection of the substituted product yields the corresponding aldehydes.51... 

Sunay, U. Fraser-Reid, B. Synthetic studies relating to the C1-C9 eastern" half of rosara-micin. Tetrahedron Lett. 1986, 27, 5335-5338. Smith, A. B. Pitram, S. M. Boldi, A. M. Gaunt, M. J. Sfouggatakis, C. Moser, W. H. Multicomponent linchpin couplings. Reaction of dithiane anions with terminal epoxides, epichlorohydrin, and vinyl epoxides efficient, rapid, and stereocontrolled assembly of advanced fragments for complex molecule synthesis./. Am. Chem. Soc. 2003, 125, 14435— 14445. 

Protection of 194 as a p-methoxybenzylether and subsequent epoxydation led to the trans-epoxide 195, which was transformed into the unsaturated aldehyde 196 by a three-reaction sequence, including regioselective oxirane opening with a 1,3-dithiane anion, hydrolysis of the dithioacetal formed, and dehydration. Chlorite promoted aldehyde oxidation, methyl ester formation, and removal of the hydroxyl protections delivered methyl (+)-shikimate 197 in a remarkable 12% yield from 193. 

Lastly for sulfur-stabilized carbanions, the synthesis of carbaprostacyclin analogues has been performed using intramolecular cyclization of a dithiane anion and bromine as the key step in the process (equation 98)642. 

The dithiane anion is a good nucleophile in SN2 reactions. After it has been alkylated, the thioacetal group can be removed by hydrolysis using Hg2+ as a Lewis acid catalyst. 

The needed substituted dithiane could itself be prepared by a similar alkylation of the unsubstituted dithiane anion. The synthesis is shown in Figure 23.2. 

The reaction of dithioesters with Grignard reagents is even more remarkable. Because sulfur and carbon have about the same electronegativity, the Grignard reagent may add to either end of the ji bond. If it adds to sulfur, the resulting anion is stabilized by two sulfur atoms, rather like the dithiane anions we have seen earlier in this chapter, and can be used as a d1 reagent. 

The compound formed from thiamine pyrophosphate and pyruvic acid is Nature s nucleophilic acetyl group. This is a d1 reagent like the dithiane anion you met in Chapter 46. 

Dichloropyrazine gave 2-chloro-6-[m-methoxy-a, a-(trimethylenedithio)-benzyl]pyrazine (196), the acetal of an acylpyrazine [2-(m-methoxyphenyl)-1,3-dithiane anion (made in situ), 2-Me—THF, -100 — 20°C 14%].1482 2-Chloropyrazine gave several Ni or Pd complexes.566,581 Also other examples.374,882... 

Vinyl epoxides can be regioselectively opened depending on the substitution at the 2-position of the 2-lithio-l,3-dithiane. Thus, the Sw2 adducts anti-204 were obtained with unencumbered dithiane anions, whereas Sa 2 adducts 205 were produced with sterically encumbered ones (Scheme 58)293. 

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