A new and high-yielding method for the regioselective preparation of 4-deoxy- and 2,4-dideoxy-2-acetamido-beta-D-threohex-3-enopyranosides has been developed. The process involves a simultaneous activation–elimination of the OH-4 group of beta-D-talopyranosides and 2-acetamido-2-deoxy- beta-D-talopyranosides, mediated by the NaH/N,N-sulfuryldiimidazole system at –30 °C. The same reaction applied on the analogous beta-D-galactopyranosides takes place without any regioselectivity, affording mixtures of hex-3- and hex-4-enopyranosides. In the case of the methyl 2,3,6-tri-O-benzyl-alfa-D-talo- and alfa-D-galactopyranosides, the corresponding 4-O-imidazylates can be isolated by quenching the reactions at –30 °C. Upon warming these crude products to room temperature, the alfa -talo-4-O-imidazylate gives the corresponding hex-3-eno derivative in very high yield, but its alfa-galacto analogue gives the hex-4-enopyranoside enol ether in poor yield. The different regiochemical outcome between the talo and the galacto series has been attributed to the stereoelectronic effect exerted, exclusively in talo-configured compounds, by the axially disposed C-2 electronegative substituent, which selectively accelerates the breaking of the antiperiplanar C(3)–H bond.
Regiospecific synthesis of 4-deoxy-D-threo-hex-3-enopyranosides by simultaneous activation-elimination of the talopyranoside axial OH-4 with the NaH/Im2SO2 system: manifestation of the stereoelectronic effect
CATELANI, GIORGIO;D'ANDREA, FELICIA
2006-01-01
Abstract
A new and high-yielding method for the regioselective preparation of 4-deoxy- and 2,4-dideoxy-2-acetamido-beta-D-threohex-3-enopyranosides has been developed. The process involves a simultaneous activation–elimination of the OH-4 group of beta-D-talopyranosides and 2-acetamido-2-deoxy- beta-D-talopyranosides, mediated by the NaH/N,N-sulfuryldiimidazole system at –30 °C. The same reaction applied on the analogous beta-D-galactopyranosides takes place without any regioselectivity, affording mixtures of hex-3- and hex-4-enopyranosides. In the case of the methyl 2,3,6-tri-O-benzyl-alfa-D-talo- and alfa-D-galactopyranosides, the corresponding 4-O-imidazylates can be isolated by quenching the reactions at –30 °C. Upon warming these crude products to room temperature, the alfa -talo-4-O-imidazylate gives the corresponding hex-3-eno derivative in very high yield, but its alfa-galacto analogue gives the hex-4-enopyranoside enol ether in poor yield. The different regiochemical outcome between the talo and the galacto series has been attributed to the stereoelectronic effect exerted, exclusively in talo-configured compounds, by the axially disposed C-2 electronegative substituent, which selectively accelerates the breaking of the antiperiplanar C(3)–H bond.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
