Aldehydes, reaction with acid dianions

The methylhydrazone of acetophenone (112) underwent ready reaction with n-butyl-lithium giving the dianion (113) reaction with acid derivatives such acid chlorides or esters resulted in pyrazole (114) formation whereas with aldehydes, pyrazolines were obtained (76SC5). With dichloromethyleneiminium salts (115), 5-dimethylaminopyrazoles... 

B-alkyl-9-BBN derivatives (p. 1077). Since only the 9-alkyl group migrates, this method permits the conversion in high yield of an alkene to a primary alcohol or aldehyde containing one more carbon." When B-alkyl-9-BBN derivatives are treated with CO and lithium tri-ferf-butoxyaluminum hydride," other functional groups (e.g., CN and ester) can be present in the alkyl group without being reduced." Boranes can be directly converted to carboxylic acids by reaction with the dianion of phenoxyacetic acid." " ... 

The Ci5 aldehyde (4) underwent a nucleophilic addition reaction with the dianion (343) of 3-methylbut-3-enoic acid the hydroxy acid formed as an intermediate was methylated with diazomethane to give (344), and this was esterified... 

HMPT exerts a similar effect in the reactions of the dianion of tiglic acid with aldehydes, but addition of HMPT to reactions of the lithium salt of crotonaldehyde cyclohexylimine with aldehydes results in a complex mixture of products. 

The first C6-C7-aldol reactions were reported by Nicolaou s group with the dianion of keto-carboxylic acid 5 (Scheme 12). Aldehydes 29a, 29b and 20b give the desired aldols 62, 63 and 66 in high yields ( ) at —78 °C. As expected, excellent control of the enolate configuration had taken place to result in a perfect C6-C7 syn relationship. Nevertheless, there was no or mini-... 

The prospects of inventing a reagent for the dianion synthon 141 might look remote but the reagent 142, both an allyl silane and an allyl stannane, does the job.39 Reaction with one aldehyde occurs at the end occupied by tin and the second, using a different Lewis acid, at the end occupied by silicon. The result is a tetrahydropyran 144 with 2,6-syn substituents, both being equatorial. 

Diazene 63 was prepared in short order from readily available starting materials. Thus, acid 64, prepared in a standard manner from the isobutyric acid dianion and 3-methyl-3-butenyl p-toluenesulfonate, was first reduced with lithium aluminum hydride and then oxidized by using PCC/Celite to afford the expected aldehyde in 88% yield. In preparation for the Diels-Alder reaction that was to be used to assemble the bicyclic framework found in 63, the aldehyde was converted to fulvene 65. Initially, we attempted to accomplish this objective using methodology... 

B.vii. Acid Dianions. All of the named reactions discussed in Section 9.4 constitute relatively minor variations of the fundamental condensation reaction of aldehydes, ketones, or acid derivatives with another aldehyde, ketone, or acid derivative. The ability to produce kinetic enolates from acid derivatives has made possible another useful modification of the enolate reaction. Carboxylic acids have an acidic proton that is removed by 1 equivalent of base to first give a carboxylate (see 226). Addition of a second equivalent of a powerful base such as a dialkylamide leads to the dianion (227). Subsequent reaction with an electrophilic species, in this case 1-bromobutane, occurred first at the more nucleophilic a-carbon to give hexanoic acid. 2 The carboxylate is usually generated with n-butyllithium and the enolate with LDA, although 2 equivalents of LDA can be used. As discussed in Chapter 8, treatment of a carboxylic acid with an excess of an organo-... 

A.V. The Noyori Open-Chain Model. In the Mukaiyama reaction, the Zimmerman-Traxler and Evans models are not satisfactory for predicting diastereoselectivity. Several open (nonchelated) transition states have been considered as useful models. The condensation reaction of carboxylic acid dianions with aldehydes indicated that anti selectivity increased with increasing dissociation of the gegenion (the cation, M+),224 When analyzing an aldol condensation that does not possess the bridging cation required for the Zimmerman-Traxler model, an aldehyde and enolate adapt an eclipsed orientation as they approach. Noyori reported syn selectivity for the reaction of a mixture of (Z)-silyl enol ether 389 and ( )-silyl enol ether 390 with benzaldehyde in the presence of the cationic tris-(diethylamino) sulfonium (TAS).225 xhis reaction is clearly a variation of the Mukaiyama reaction, which does not usually proceed with good diastereoselectivity... 

Dihydroisocoumarins are conveniently obtained from the reaction of aldehydes and ketones with the dianions derived from o-toluic acids, though the products are not always stereochemically pure (94SC779). However, enantiomerically pure dihydroisocoumarins result from the stereoselective reduction of (arene)-tricarbonylchromium cmnplexes of homobenzylic ketones by DIB ALH, followed by oxidation of the resulting lactols (94CCS01). 

The dianions of a-halocarboxylic acids give epoxy acids (called glycidic acids) on reaction with aldehydes and ketones. 

In a novel alkylating method that has been published, the dianion of carboxylic acid (177) was subjected, in a first step, to a nucleophilic addition reaction with the Cjo aldehyde ester (169) to give the unstable hydroxy acid (178) (Trost and Fortunak, 1981). The acetylated acid (179) smoothly underwent decarboxylative elimination to give ethyl retinoate (24). 

Some interesting results have come out of a study of the variations in stereochemistry erythrojthreo ratio) of jS-hydroxy-acids produced by condensations between carboxylic acid dianions and aldehydes. The reactions seem not to be controlled by complexation between the metal counterions and the incoming aldehyde but rather by HOMO(dianion)-LUMO(aldehyde) interactions with changes in the metal counterion affecting the HOMO(dianion) level. ... 

A new synthesis of aldehydes with 2-methyl-2-thiazoline has the advantage of releasing the aldehydes from the thiazolidine intermediate under neutral conditions . Acetylene derivatives can be obtained from aldehydes via dibromomethylene compounds Novel reactions of alkynes with cationoid electrophiles have been published. -Diketones and 2-ketoalkoximes can be obtained by this reaction from acid chlorides and aliphatic nitro compounds respectively Addition of aldehydes to activated carbon-carbon double bonds occurs smoothly in the presence of cyanide ions as catalysts . Poly- -carbonyl compounds have been prepared by condensation of two anions, whereby the enolate salt of a y8-keto ester condenses as an electrophilic anion with strong nucleophiles such as the dianion of benzoylacetone. ... 

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

A completely different dipolar cycloaddition model has been proposed39 in order to rationalize the stereochemical outcome of the addition of doubly deprotonated carboxylic acids to aldehydes, which is known as the Ivanov reaction. In the irreversible reaction of phenylacetic acid with 2,2-dimethylpropanal, metal chelation is completely unfavorable. Thus simple diastereoselectivity in favor of u f/-adducts is extremely low when chelating cations, e.g., Zn2 + or Mg- +, are used. Amazingly, the most naked dianions provide the highest anti/syn ratios as indicated by the results obtained with the potassium salt in the presence of a crown ether. 

Organoytterbium chemistry has been developed in the last 20 years, although the development rate is much slower than the other lanthanides like samarium or cerium. Dianionic complexes that are produced from the reaction of ytterbium with diaryl ketones react with various kinds of electrophiles including carbon-heteroatom unsaturated bonds.35 Phenylytterbium iodide, a Grignard-type reagent, is known to have reactivity toward carbon dioxide,36 aldehydes, ketones,37,37 and carboxylic acid derivatives38,3811 to form the corresponding adducts respectively. 

A few years ago, Blagonev and Ivanov described the bis-deprotonation of aryl acetic acids by Grignard reagents. These magnesinm dianions, known as Ivanov reagents, react with aldehydes and ketones. Reaction between dianions of phenylacetic acid and benzaldehyde yields the anti S-hydroxy acid as the major diastereomer anti/syn 69/22) (equation 113). This result is in agreement with the formation of a cyclic chair-like transition state according to the model of Zimmerman-Traxler . 

Another route to thioaldehyde and thioketone complexes uses the tungstate [W(CO)5SH] as the precursor. When [W(CO)5SH] was treated with ketones in the presence of trifluoroacetic acid, thioketone complexes [W(CO)5 S = C(R1)R2 ] were formed. Analogously, thiobenzaldehyde complexes were obtained from [W(CO)sSH]- and benzaldehydes bearing electron-releasing para substituents. Benzaldehyde, benzaldehydes with electron-withdrawing substituents, and aliphatic aldehydes did not react. Presumably, the binuclear dianion [p,-S W(CO)5 2]2 is an intermediate in the reaction, as on acidification of a mixture of [ju,-S W(CO)5 2]2 and p-N, A -dimethylaminobenzaldehyde the thioaldehyde complex [W(CO)5 S = C(C6H4NMe2-p)H ] is formed.143... 

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