A new synthesis of (-)-esermethole, based on the asymmetric alkylation at C(3) of racemic 1,3-dimethyl-5-methoxyoxindole (3), is described. The chloroacetyl derivatives of (-)-menthol and (S)-N-methyl-(1-phenylethyl) amine were chosen as chiral alkylating agents and used under different reaction conditions (temperature, solvent and base). In particular, the latter reacted with 3 in toluene at 10°C, in the presence of t-butyllitium, giving (3S,1′S)-N-methyl-N-(1′-phenylethyl)-1,3-dimethyl-5-methoxyoxindol-3-ilacetamide (10) with a 63% d.e.. This intermediate was easily separated from the undesired minor (3R,1′S) diastereomer (11) and converted to (-)-esermethole (99.6% e.e.) in two steps.
New asymmetric synthesis of (−)-esermethole / M. Pallavicini, E. Valoti, L. Villa, I. Resta. - In: TETRAHEDRON-ASYMMETRY. - ISSN 0957-4166. - 5:3(1994), pp. 363-370. [10.1016/S0957-4166(00)86207-2]
New asymmetric synthesis of (−)-esermethole
M. PallaviciniPrimo
;E. ValotiSecondo
;
1994
Abstract
A new synthesis of (-)-esermethole, based on the asymmetric alkylation at C(3) of racemic 1,3-dimethyl-5-methoxyoxindole (3), is described. The chloroacetyl derivatives of (-)-menthol and (S)-N-methyl-(1-phenylethyl) amine were chosen as chiral alkylating agents and used under different reaction conditions (temperature, solvent and base). In particular, the latter reacted with 3 in toluene at 10°C, in the presence of t-butyllitium, giving (3S,1′S)-N-methyl-N-(1′-phenylethyl)-1,3-dimethyl-5-methoxyoxindol-3-ilacetamide (10) with a 63% d.e.. This intermediate was easily separated from the undesired minor (3R,1′S) diastereomer (11) and converted to (-)-esermethole (99.6% e.e.) in two steps.
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