Synthesis of propargyl alcohol derivatives involves stereoselective acylation of a racemic propargyl alcohol in the presence of a lipase, solvent and acylating agent, via a Mitsunobu reaction on the mixture of alcohol and acetate

摘要

Synthesis of propargyl alcohol derivatives of R configuration. Synthesis of organic compounds of R configuration of formula (I) involves: (1) contacting a compound of formula (II) with lipase in the presence of an acylating agent and a solvent to obtain a mixture of corresponding R acetate and S alcohol (A); (2) treating (A) with a dialkyl azodicarboxylate in the presence of trialkyl or triaryl phosphines and a nucleophilic compound to convert the S alcohol into R acetate by inversion of configuration; (3) obtaining the corresponding R alcohol by transesterification in the presence of methanol and sodium carbonate followed by a crystallization; and (4) coupling the alcohol thus obtained with a phenyl derivative of formula (III) to obtain ester which possibly undergo a saponification reaction to give (I) (where R2 is H). R1 = H, 1-6C alkyl, aryl, halo or -OR3; R2, R3 = H or 1-6C alkyl; and X = halo.