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Regiospecific Synthesis of 4‐Deoxy‐ D ‐ threo ‐hex‐3‐enopyranosides by Simultaneous Activation–Elimination of the Talopyranoside Axial 4‐OH with the NaH/Im 2 SO 2 System: Manifestation of the Stereoelectronic Effect
Author(s) -
Attolino Emanuele,
Catelani Giorgio,
D’Andrea Felicia
Publication year - 2006
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200600526
Subject(s) - chemistry , regioselectivity , yield (engineering) , stereochemistry , substituent , stereospecificity , cyclohexane conformation , enol , ether , medicinal chemistry , organic chemistry , catalysis , molecule , hydrogen bond , materials science , metallurgy
A new and high‐yielding method for the regioselective preparation of 4‐deoxy‐ and 2,4‐dideoxy‐2‐acetamido‐β‐ D ‐ threo ‐hex‐3‐enopyranosides has been developed. The process involves a simultaneous activation–elimination of the OH‐4 group of β‐ D ‐talopyranosides and 2‐acetamido‐2‐deoxy‐β‐ D ‐talopyranosides, mediated by the NaH/ N , N ′‐sulfuryldiimidazole system at –30 °C. The same reaction applied on the analogous β‐ 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‐α‐ D ‐talo‐ and α‐ 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 α‐ talo ‐4‐ O ‐imidazylate gives the corresponding hex‐3‐eno derivative in very high yield, but its α‐ 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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)