Maria Alice Bockelmann

The Mannich-like addition of chiral and achiral titaniun enolates derived from N- propionyl oxazolidin-2-ones to 5- and 6- membered N-acyliminium ions afforded 2- substituted pyrrolidines in moderate to good diastereoisomeric ratio (5:1 to 14:1) while lower diastereoselection was generally observed in the formation of the corresponding 2- substituted piperidines (~2:1). On the other hand, better selectivity was achieved with 6- membered N-acyliminium ions in the addition of chiral titanium enolate derived from the corresponding N-acetyl oxazolidin-2-ones (for 6-membered ring 3.5:1; and for 5-membered ring 1.1:1). The stereochemical outcome was found to be modulated by the nature of the cyclic N-acyliminium ion (5 or 6-membered), of the carbamate (N-Boc, Cbz, COOMe) and N-acyl groups in the enolate (R=H, Me). Only one isomer of 2-substituted pyrrolidines was obtained in the adittion of chiral enolates derived from N-phenilacetyl and 4-chloro butanoyl-oxazolidin-2-ones and better selectivity was observed with 6-membered N- acyliminium ion (8-12:1 and 5: 1, respectively). The preferential lk approach seems to be dictated mainly by the minimization of non-bonding interactions between the N-acyl group in the chlorotitanium (IV) enolate and the carbamate and methylene groups in the cyclic N-acyliminium ion. In the addition of the chiral enolate derived from (4R)-N-acyl oxazolindin-2-ones the major isomer displayed (1 S, 2S) absolute configuration and the minor (1 S, 2R). Finally, the chiral adducts were used in the studies of the syntheses of aIkaloids (isoretronecanol, 8-epitashiromine and lupinine) and in the asymmetric synthesis of (2R, 2 R)-methyl-fenidate hydrochloride.

"Adição diastereosseletiva de enolatos de titanio a ions N-aciliminio ciclicos : estudos visando a sintese de alcaloides e a sintese assimetrica do farmaco cloridrato de (+)-fenidato de metila"

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