Intramolecular Ene Reactions. Stereo- and Enantioselective Synthesis of Spirolactams through Thermolysis of Enamino Carboxamides

A new and facile access to spirolactams based on the thermal rearrangement of tertiary and secondary enamino carboxamides has been developed. The enamine group of an enamino carboxamide, in which no electron-withdrawing group is present in the enophile, can be involved in the ene reaction and the enamino carboxamide can be transformed into enamino or imino spirolactams. In the case of secondary carboxamido enamines, the diastereoselectivity is higher than 98%. If chiral nonracemic analogs are utilized, 50−54% enantiomeric excesses can be achieved in the final products

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

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