Aromatization of 1,6,7,7a-Tetrahydro-2<i>H</i>-indol-2-ones by a Novel Process. Preparation of Key-Intermediate Methyl 1-Benzyl-5-methoxy-1<i>H</i>-indole-3-acetate and the Syntheses of Serotonin, Melatonin, and Bufotenin

Imine 7 of 1,4-cyclohexanedione mono-ethylene ketal 6 was reacted with maleic anhydride, affording the cyclized adduct 8. Methyl esterification of 8, accompanied by transacetalization, led to the dihydrooxindole derivative 10. Aromatization of 10 was then accomplished with POCl3, leading directly to the key-intermediate title compound 11 in 74% yield from ketone 6. Serotonin, melatonin, and bufotenin were then obtained by standard reactions

Reaction of Cyclohexanone Benzylimines with Ethylidenemalonate Diesters. Diphenyl 2-Ethylidenemalonate: A Highly Electrophilic Synthetic Equivalent of Crotonic Esters

The diastereoselective Michael alkylation of α-substituted and α,α‘-disubstituted cyclohexanone benzylimines with ethylidenemalonate diesters was carried out for mechanistic and synthetic purposes. In the first case, an inverse regioselectivity occurred in comparison with what is generally observed since the Michael adducts resulted from alkylation of the non substituted enamine tautomer. With α,α‘-disubstituted imines, in all cases, the stereochemistry of the major diastereomer was the one anticipated from a mechanism including a chairlike complex approach with a preferred exo position for the β-methyl group of the ethylidenemalonic acid diesters. Furthermore, diphenyl 2-ethylidenemalonate 4 was found to be a highly electrophilic synthetic equivalent of crotonic esters

Tautomerism of α,β-Ethylenic Imines and Their Reactivity toward Electrophilic Olefins

The equilibrium between α,β-ethylenic imines and their secondary enamine tautomer form has been demonstrated for the first time. These imines react with electrophilic olefins to give Michael adducts at either the α or the α‘ position of the imine function

Enantioselective Michael Reactions of Chiral Secondary Enaminoesters with 2-Substituted Nitroethylenes. Syntheses of <i>trans,trans</i>-2,4-Disubstituted Pyrrolidine-3-carboxylates

The Michael reaction of chiral 3-substituted secondary enaminoesters with 2-substituted nitroethylenes leads to (Z)-adducts, with good to excellent diastereoselectivity. The nitro group of these adducts was catalytically reduced to give, after cyclization and chiral amine elimination, pyrrolines or pyrrolidines after further reduction. In particular, the syntheses of ethyl (2R,3S,4S)-2,4-dimethylpyrrolidine-3-carboxylate and ethyl (2R,3R,4S)-2-(4-methoxyphenyl)-4-(3,4-(methylenedioxy)phenyl)pyrrolidine-3-carboxylate are described