Enantiopure 3‐((R)‐ and 3‐((S)‐1‐phenylethyl)‐4‐oxazoline‐2‐ones were evaluated as chiral building blocks for the divergent construction of heterocycles with stereogenic quaternary centers. The N‐(R)‐ or N‐(S)‐1‐phenylethyl group of these compounds proved to be an efficient chiral auxiliary for the asymmetric induction of the 4‐ and 5‐positions of the 4‐oxazolin‐2‐one ring through thermal and MW‐promoted nucleophilic conjugated addition to Michael acceptors and alkyl halides. The resulting adducts were transformed via a cascade process into fused six‐membered carbo‐ and heterocycles. The structure of the reaction products depended on the electrophiles and reaction conditions used. Alternative isomeric 4‐methylene‐2‐oxazolidinones served as chiral precursors for a versatile and divergent approach to highly substituted cyclic carbamates. DFT quantum calculations showed that the formation of bicyclic pyranyl compounds was generated by a diastereoselective concerted hetero‐Diels‐Alder cycloaddition.
New and efficient strategies for the conversion of 4-oxazolin-2ones into 1-methyl and 1,4-dimethyl 3-formylcarbazoles are herein described. Highly convergent cascade and one-pot processes afforded the corresponding diarylamines, as in situ formed synthetic intermediates or final products in high overall yields. Special attention was given to the synthesis of methylated carbazoles by reacting 4,5-dimethyl-4-oxazolin-2-ones with enones under microwave irradiation. The carbazole scaffold was provided by the palladium(II)-catalyzed double CÀ H activation to generate oxidative cyclization of diarylamines. This methodology allowed for formal total syntheses of four naturally occurring pyrido[4,3-b]carbazole alkaloids ellipticine, 9-methoxyellipticine, olivacine, and 9-methoxyolivacine.
Palladium-catalyzed functionalization was presently performed
on
two building blocks: 4-oxazolin-2-ones and 4-methylene-2-oxazolidinones.
Direct Heck arylation of 4-oxazolin-2-ones led to a series of 5-aryl-4-oxazolin-2-ones,
including analogues with N-chiral auxiliary, in an almost quantitative
yield. The Pd(II)-catalyzed homocoupling reaction of 4-oxazolin-2-ones
provided novel heterocyclic across-ring dienes. Meanwhile, the intramolecular
cross-coupling of N-aryl-4-methylene-2-oxazolidinones
furnished a series of oxazolo[3,4-a]indol-3-ones.
Further functionalization of 4-methylene-2-oxazolidinones afforded
substituted indoles and heterocyclic-fused indoles with aryl, bromo,
carbinol, formyl, and vinyl groups. A computational study was carried
out to account for the behavior of the formylated derivatives. The
currently developed methodology was applied to a new formal total
synthesis of ellipticine.
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