Acylation carbanions

Schlessinger and his co-workers have outlined an alternative approach to the fused five-membered ring system found in pentalenolactone which uses an intramolecular carbanion acylation reaction to form the second five-membered ring (Scheme 15). 

Surprisingly carbonyl-substituted carbanions of phosphonates, in which the negative charge is delocalized over two oxygen atoms, are much more nucleophilic than the corresponding phosphoranes. This effea has first been observed by Homer, and has often been utilized in the synthesis of acylated olefins (R.D. Clark, 1975). 

Carbanions stabilized by phosphorus and acyl substituents have also been frequently used in sophisticated cyclization reactions under mild reaction conditions. Perhaps the most spectacular case is the formation of an ylide from the >S-lactam given below using polymeric Hflnig base (diisopropylaminomethylated polystyrene) for removal of protons. The phosphorus ylide in hot toluene then underwent an intramolecular Wlttig reaction with an acetyl-thio group to yield the extremely acid-sensitive penicillin analogue (a penem I. Ernest, 1979). 

The reduction of o-nitrophenyl acetic acids or esters leads to cyclization to oxindoles. Several routes to o-nitrophenylacetic acid derivatives arc available, including nitroarylation of carbanions with o-nitroaryl halides[2l,22] or trif-late[23] and acylation of o-nitrotoluenes with diethyl oxalate followed by oxidation of the resulting 3-(u-nitrophenyl)pyruvate[24 26]. 

The main Uab synthetic pathway is illustrated in Scheme 6.1 and corresponds to C-acylation of an o-aminobenzyl carbanion equivalent. Acylation is normally followed by in situ cyclization and aromatization. This route is therefore closely related to the cyclizations of o-aminobenzyl ketones described in Section 2.3 but the procedures described here do not involve isolation of the intermediates. 

Reactions with Acyl Garbanion Equivalents. Alkyl substituted carbanions CRXY with potential leaving groups X, Y, and acyl carbanion equivalents or CHRX (342) react with alkylboranes, providing products with mixed alkyl groups derived from both reagents. 

Bis(dimethylamino)carboniiim bifluoride catalyzes the addition of acyl fluorides to perfluoroalkenes by the generation of readily acylated carbanions [4] (equation 4)... 

On the basis of these findings, the reaction of acyl imines with methanesulfony 1 chloride-triethylamine is not expected to proceed via a sulfene intermediate as previously proposed [99]. Again, a carbanion intermediate accounts nicely for the experimental facts. The electrophihcity of the hetero-l,3-diene is exdemely high, therefore the carbanion, formed on reaction of triethylamme with methanesulfonyl chloride, should undergo nucleophilic attack at C-4 of the hetero-1,3-diene faster than sulfene formabon by chloride elimination. 

The thenyl cyanides are of great importance for the preparation of thiophene derivatives. Because of the acidifying effects of both the thienyl and of the cyano groups, carbanions are easily obtained through the reaction with sodamide or sodium ethoxide, which can be alkylated with halides, carbethoxylated with ethyl carbonate, or acylated by Claisen condensation with ethyl... 

In a similar scheme, acylation of 2-methoxynaphthalene gives ketone, 15. This is then converted to the acetic acid by the Wilgerodt reaction. Esterification, alkylation of the carbanion (sodium hydride methyl iodide), and finally saponification affords naproxen (17). The intense current effort on nonsteroid antiinflammatory agents and acrylacetic acids in particular make... 

CHBr3 or iodoform, CHI3). Note that the second step of the reaction is a nucleophilic acyl substitution of CX3 by OH. That is, a halogen-stabilized carbanion acts as a leaving group. 

In this section alkylation, Michael additions, hydroxyalkylation (reaction with carbonyl compounds), aminoalkylation, acylation and some other reactions of a-sulphinyl carbanions will be discussed. 

From the synthetic point of view the most important a-sulphinyl carbanions are the anions derived from dithioacetal S-oxides which may be considered as synthons of acyl... 

Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

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