Oxindole deprotonation

Other important compounds include oxindole, which is the lactam of 2-aminophenylacetic acid. This compound has an active methylene group, which can be deprotonated with a base such as sodium ethoxide, and the anion that is formed can be alkylated with- a variety of electrophiles (Scheme 7.20). In the case of benzaldehydes, the initially formed aldols are unstable and these dehydrate readily to the corresponding (E)- and (Z)-(benzy lidene)oxindoles. 

A simple and versatile method for the synthesis of aziridinium salts involves the reaction of a diazoalkane with an iminium salt (82TL285, B-83MI 102-01). The aziridinium salt thus formed was oxidized to an aminoaldehyde by DMSO (Scheme 39). A key step in the preparation of the oxindole alkaloid gelsemine (104) involves the carbonylation of the unsaturated aziridinium ion (103) with disodiumtetracarbonyl picrate-dioxane complex under a CO atmosphere followed by base-promoted epimerization and deprotonation (Scheme 40) <92JOC1035>. 

Oxindole exists as the carbonyl-tautomer, the hydroxy 1-tautomer ( 2-hydroxyindole ) being undetectable. There is nothing remarkable about the reactions of oxindole for the most part it is a typical 5-membered lactam, except that deprotonation at the p-carbon (pA a 18) occurs more readily than with simple amides, because the resulting anion is stabilised by an aromatic indole resonance contributor. Such anions will react with electrophiles like alkyl halides and aldehydes at the p-carbon, the last with dehydration and the production of aldol condensation products. Oxindoles can be oxidised to isatins (20.13.3) via easy 3,3-dibromination, then hydrolysis. Bromination of oxindole with A -bromosuccinimide gives... 

A unique inversion on the theme of trapping an electrophile with enolate nucleophile has been reported by Krishnan and Stoltz who have installed all-carbon quaternary centers at oxindoles, e.g., 42, in racemic fashion through the treatment of electrophilic 3-halooxindoles with nucleophilic malonates, e.g., 40-41, using DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) for the deprotonation step (Scheme 11) [28]. An asymmetric variation of the chemistry in Scheme 11 has been reported by the same group who constructed enantioeiuiched oxindoles using catalytic Cu(ll)-Lewis acid and a chiral bis(oxazoline) ligand [29]. 

For this reason, the only literature example regarding the use of nitroalkenes as Michael acceptors in enantioselective Michael reactions under PTC conditions is related to the use of oxindoles as pro-nucleophiles (Scheme 5.31). In this context, using deuterium labeling experiments, it was found that oxindoles underwent fast deprotonation in neutral aqueous media only in the... 

The iron-catalysed reaction of heteroarenes, including indoles, pyrroles, thiophene, and furan, with 3-methyl-2-quinonyl boronic acids allows the formation of alkylated products, such as (68), rather than the more usual alkenylated products. The unusual alkylation, at the 5-position, of oxindoles to give products such as (69) has been reported using the acid-catalysed reaction with benzylic alcohols in nitromethane. Silylation of indole, at the 3-position, to give (70) has been achieved using a cationic ruthenium(II) sulfide complex as a catalyst. A sulfur-stabilized silicon electrophile is formed resulting in a Wheland intermediate which is deprotonated by sulfur atom. ... 

Further reaction of A -chloroaniline 6 with ethyl (methyl)thioacetate yields azasulfonium ion 7, which forms ylide 8 upon deprotonation with triethylamine. After the ylide undergoes a [2,3]-Sommelet-Hauser-like rearrangement, a proton transfer and subsequent rearomatization produces the intermediate aniline derivative 9, which upon cyclization forms a transient tetrahedral anion. Collapse of the anion with loss of ethoxide produces the stable oxindole derivative 2. Removal of the methyl thiol functionality with Raney nickel produces the final product 3. 

A mechanistic rationalization for this reaction is presented in Scheme 5.48. Domino process is initiated with generation of key intermediate 152, which undergoes a 1,4-addition of a deprotonated oxindole to form 153. After H-migration and following aldol reaction with another molecule of alkynyl aldehyde, intermediate 155 is formed. Subsequent lactonization delivers prodnct 66 and regenerates NHC for the next catalytic cycle. The stereochemistry of the products may be determined by the most sterically favored chair transition state in 155. 

There has been a summary of computational and experimental studies of the use of palladium complexes with A -heterocyclic carbenes (NHCs) in the asymmetric coupling of -hybridized carbon-hydrogen bonds with aryl halides. It has been shown that the electronic and catalytic properties of NHCs fused to porphyrins may be modified by varying the inner metal in the porphyrin. A DPT study of the use of palladium-NHC complexes in the asymmetric intramolecular a-arylation of 2-bromoaryl amides to give 3,3-disubstituted oxindoles (101) has been reported. The likely pathway involves insertion of the palladium into the arene-bromine bond to form a palladacycle which deprotonates to give an (9-enolate. Conversion into the C-enolate followed by reductive elimination gives the product. The intramolecular reaction of 0 a cyclopropane carbon-hydrogen bond in a 2-bromoanilide derivative has been used to form cyclopropyloxindoles, (102), in a palladium-catalysed, silver-mediated reaction. 

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