(3R)-(p-Tolylsulfinyl)-N-methoxyacetimidic Acid Ethyl Ester

[95614-76-9]  · C12H17NO3S  · (3R)-(p-Tolylsulfinyl)-N-methoxyacetimidic Acid Ethyl Ester  · (MW 255.37)

(asymmetric aldol-type condensation1)

Alternate Name: ethyl (p-tolylsulfinyl)-N-methoxyacetimidate.

Physical Data: [a]D = +28° (c = 1, CHCl3).

Preparative Method: prepared in 89% yield by reacting the lithium enolate of ethyl N-methoxyacetimidate with (-)-(S)-menthyl p-toluenesulfinate (see (-)-(1R,2S,5R)-Menthyl (S)-p-Toluenesulfinate) (eq 1).1

Aldol-Type Condensation.

Aldol-type condensation of the lithium enolate of ethyl (R)-(p-tolylsulfinyl)-N-methoxyacetimidate (prepared with n-Butyllithium) with aldehydes affords, after desulfurization with Raney Nickel, b-hydroxy esters with high enantioselectivity (eq 2).1

Anti diastereoselectivity gives the optically active (S)-b-hydroxy ester while syn diastereoselectivity leads to the (R)-b-hydroxy ester, via a chelated six-membered transition state (eq 3). Since the anti intermediate is more stable, the (S)-b-hydroxy ester predominates under thermodynamic conditions (Table 1, entry 1). Higher diastereoselectivity is achieved by changing the counterion from lithium to a more chelating one such as zinc (Table 1, entry 2). On the other hand, in order to obtain diastereoselection under kinetic control, zirconium enolates (prepared by treating the lithium enolate with Dichlorobis(cyclopentadienyl)zirconium) are used, leading to the (R)-b-hydroxy ester (Table 1, entry 3) in high yield.

1. Bernardi, A.; Colombo, L.; Gennari, C.; Prati, L. T 1984, 40, 3769.

Guy Solladié & Françoise Colobert

University Louis Pasteur, Strasbourg, France

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