Stereoselective route to produce tris-O-substituted-(E)-1-(3,5-dihydroxyphenyl)-2-(4-hydroxyphenyl)ethene, an intermediate in the synthesis of trans-resveratrol

A stereoselective process for the preparation of substituted diarylethenes represented by general formula (I)

• a) wherein R1, R2 and R3 are independently represented as alkoxyalkyl, allyl, vinyl, silyl, formyl, acyl, arylalkyl or substituted arylalkyl groups, or a combination thereof, the said process comprising the steps of:
• b) treating a compound of formula (III) with a halogenating agent in an organic solvent under nitrogen atmosphere for a period of 60-180 minutes,
• wherein R1, R2 and R3 are as defined above,
• c) removing the precipitated by product of step (a) by filtration to get a solution,
• d) evaporating the solution of step (b) to remove the solvent, to obtain a residue,
• e) dissolving the residue of step (c) residue in an dry organic solvent,
• f) treating the solution of step (d) solution with an oxidizing agent, maintaining the temperature between −30° C. to +60° C. for a time period of 15-300 minutes,
• g) quenching the reaction mixture of step (e) with ice, thereby forming an organic layer and an aqueous layer,
• h) separating the organic layer of step (f),
• i) washing the organic layer of step (g) with an aqueous alkali bicarbonate solution followed by water,
• j) charcoalizing the organic layer of step (h), filtering and removing the organic solvent under vacuum to obtain compound of general formula (IV)
• wherein X is halogen and R1 to R3 as defined above
• j) treating the compound of formula (IV) of step (i) with a phase transfer catalyst and a base in an organic solvent at a temperature range of −60° to +110°, for a period of 15-480 minutes,
• k) adding water to the reaction mixture of step (j),
• l) separating the organic layer from the reaction mixture of step (k), charcoalizing, filtering, and evaporating the organic layer to obtain a residue, and
• m) treating the residue of step (l) with alcoholic solvent at a temperature range of 25°-32° C. for 1-3 hours to obtain exclusively a stereoselective trans form tris-O-substituted (E)-1-(3,5-dihydroxyphenyl)-2-(4-hydroxyphenyl)ethene represented by general formula (I).