Dianions generation

Dianion formation from 2-methyl-2-propen-l-ol seems to be highly dependent on reaction conditions. Silylation of the dianion generated using a previously reported method was unsuccessful in our hands. The procedure described here for the metalation of the allylic alcohol is a modification of the one reported for formation of the dianion of 3-methyl-3-buten-l-ol The critical variant appears to be the polarity of the reaction medium. In solvents such as ether and hexane, substantial amounts (15-50%) of the vinyl-silane 3 are observed. Very poor yields of the desired product were obtained in dirnethoxyethane and hexamethylphosphoric triamide, presumably because of the decomposition of these solvents under these conditions. Empirically, the optimal solvent seems to be a mixture of ether and tetrahydrofuran in a ratio (v/v) varying from 1.4 to 2.2 in this case 3 becomes a very minor component. 

For some halides, it is advantageous to use finely powdered lithium and a catalytic amount of an aromatic hydrocarbon, usually naphthalene or 4,4 -di- -bu(ylbiphcnyl (DTBB).28 These reaction conditions involve either radical anions or dianions generated by reduction of the aromatic ring (see Section 5.6.1.2), which then convert the halide to a radical anion. Several useful functionalized lithium reagents have been prepared by this method. In the third example below, the reagent is trapped in situ by reaction with benzaldehyde. 

Selenophene was also obtained as the main component in the reaction between vinylacetylene and the selenium dianion, generated from elemental selenium (Se8), in dimethyl sulfoxide-potassium-water at 100-120°C.5° Bis-y,y-dimethylallenyl selenide (18) is converted by spontaneous cyclo-aromatization to 3-isopropenyl-4-isopropylselenophene (19).51 Two mechanisms are shown in Scheme 3. 

Thioamide dianions (generated by the highly efficient reaction of iV-benzyl thioamides with 2 equiv. of BuLi) take place alkylation, allylation and silylat-ion selectively at the carbon atom adjacent to the nitrogen atom of the thioamide dianions (Scheme 38).77... 

A convenient way of six-carbon homologation of aldehydes and ketones is the nucleophilic addition of the dianion generated from sorbic acid, (2 ,4 )-hexa-2,4-dienoic acid and subsequent dehydration to form the corresponding trienoic acid (equation 43)81. The 3-methyl analogue of sorbic acid has been used in a similar fashion for a short synthesis of vitamin A carboxylic acid (equation 44)82. 

In 1988, an improved synthesis of orlistat (1) was reported by the Hoffmann-La Roche discovery chemistry. The scheme involved a pivotal P-lactone 14. In the approach, an aldol condensation of aldehyde 7 with the dianion generated from octanoic acid and two equivalents of LDA. After tosylic acid-facilitated lactonization and Jones oxidation, the resultant lactone 14/14 was hydrogenated to establish two additional chiral centers. A battery of somewhat tedious protections and deprotections transformed 15 to P-lactone 19 via the intermediacy of 16,17, and 18. Six additional steps then converted P-lactone 19 to orlistat (1). This route may provide better overall yield in comparison to the previous scheme. However, too many protections and deprotections render this approach less elegant and not very practical for large-scale process. 

Dianion formation from 2-methyl-2-propen-l-ol seems to be highly dependent on reaction conditions. Silylatlon of the dianion generated using a previously reported method was unsuccessful in our hands. The procedure... 

A powerful route to dithiolene complexes employs alkenedithiolate dianions generated by the hydrolysis of cyclic unsaturated dithiocarbonates, which are formally called l,3-dithiole-2-ones. Representative of the many examples (60), the base hydrolysis route has been used to prepare the ferrocene-substituted dithiolene Ni[S2C2H(C5H4)FeCp]2 (61), the sulfur-rich dithiolene [Ni(S2C2S2-C2H4)2F (62), the cyano(dithiolenes) fra s- Ni[S2C2H(CN)]2 (n = 1, 2) (63), 2,3-thiophenedithiolates [Au(S2C,H2S)21 (64), and the tris(styryldithiolate)... 

Carbolithiation reactions of ketone a,-dianions, generated by the above amine-free method with several alkenes, such as styrenyl derivatives, vinyl sulfides and vinylsilanes, can lead to the generation of ketone a,5-dianions (Scheme 15)14. For example, when one equivalents of triphenylvinylsilane was treated with a ketone a,-dianion, in THF, at 0 C for 1 h and the resulting reaction mixture was quenched by 2.2 mol equivalents of trimethylchlorosilane, the corresponding bis-silylated enol silyl ether was obtained. Substituted styrenyl derivatives, such as 1,1-diphenylethylene and cinnamyl alcohol, also underwent a smooth carbolithiation to give the corresponding ketone a,5-dianions. Similar addition reactions of ketone a,f)-dianions to vinyl phenyl sulfide took place smoothly to give a,5-dianions with a sulfur attached in the 5-position. 

Carotene has been prepared by treating the a,a -dianion generated from starting sul-phone with bromine or iodine followed by rearrangement (equation 25). Utilizing the Ramberg-Backlund reaction, an interesting cyclic enediyne has been made (equation 26). ... 

In the laboratory of D.R. Williams, a carbanion methodology for the alkylations and acylations of substituted oxazoles was investigated. The study showed that the monoalkylation of the dianion generated from 2-(5-oxazolyl)-1,3-dithiane exclusively led to the substitution of the carbon adjacent to sulfur. However, acylation reactions of the dianion afforded 4,5-disubstituted oxazoles. These new products presumably arose from carbonyinitrile ylide intermediates, which were generated by the selective C-acylation of a ring-opened dianion tautomer. This is the first example of a base-induced, low-temperature Cornforth rearrangement. 

Inverse addition of the dianion generated from 380 to lactate 379 results in a 2 1 mixture of diastereomers 381 and 382. After separation of the mixture by column chromatography, the major diastereomer 381 is lactonized by acidic removal of the MOM group. 

In the first step, the dianion generated from 17 was alkylated with homoallyl bromide to give the corresponding j8-ketophosphonate which, under typical di-... 

Dianion Generation. Lithium naphthalenide efficiently de-protonates alkynyloxy " and carboxylate anions (eq 5). In addition, the previously mentioned phenomenon of reductive metalation has been exploited to access dianions fromhalohydrins, -halo carboxylic acids, and -halo carboxamides, and even trianions from -dihalo alcohols. A major pathway for the polyanionic species is -elimination (eq 6) when such processes can be avoided, the polyanions react according to Hauser s rule (eq... 

Dianion Generation. A combination of w-BuLi and LN can be used to generate dianionic intermediates containing /3-heteroatoms, without concern for rapid El elimination (eq 19). Bridged bicyclic cort5)ounds can be accessed by the double reduction of aromatic diesters by LN to generate stable bis-enolates, followed by double alkylation with a,< -electrophiles (eq 20). ... 

Abdul-Rahrm O, Simonov AN, Ruther T, Boas JF, Toiriero AAJ, Collins DJ, PerlmutterP, Bond AM (2013) The observation of dianions generated by electrochemical reduction of trans-stilbenes in ionic liquids at room temperature. Anal Chem 85 6113-6120. doi 10.1021/ac400915z... 

Scheme 2.113. The Peterson reaction of silyl dianions generated by conjugate addition of organometallic reagents to a 1-amidoethenylsilane.

Our synthetic target therefore turned briefly to PNU 141571, the synthesis of which is shown in Scheme 5. It begins with a displacement on the deactivated monochloropyrimidine 3 with ethanolamine. Safety studies had confirmed our suspicions about the thermal hazards associated with this displacement, hazards typical for displacements in this series. Moreover, activation as the amide base was unsuccessful in the present case. Attempted displacement with either the monoanion or the presumed dianion (generated by addition of one or two equivalents of n-butyllithium to ethanolamine) afforded the ether exclusively. 

An alternative to 138 and 122 is (R)- or (5)-2-hydroxy-l,2,2-triphenylethyl acetate ((/ )-or (5)-HYTRA) (14.3). a chiral acetate which does not need an auxiliary heteroatomic substituent. Compound 143 is readily available through acylation of 1,2,2-triphenyl-1,2-ethandiol with acetyl chloride or acetic anhydride. Its dianion, generated by double deprotonation with LDA and transmetallation with MgBr2 or Mgl2, reacts with aliphatic and aromatic aldehydes to give )8-hydroxy acid derivatives with diastereomeric ratios ranging from 92 8 to 98 2 . The crude adducts can be readily purified by crystallization. Removal of the auxiliary can be accomplished either hydrolytically (KOH, aq. MeOH) or transesterification (MeONa, MeOH/THF) to provide the respective j8-hydroxy acid/ester in enantiomerically pure form. 

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