Single step enantioselective process for the preparation of 3-substituted chiral phthalides

摘要

The present invention discloses single step, highly enantioselective catalytic oxidative cyclization process for the synthesis of 3-substituted chiral phthalides. In particular, the invention discloses asymmetric synthesis of chiral phthalides via synergetic nitrile accelerated oxidative cyclization of o-cyano substituted aryl alkenes in high yield and enantiomeric excess (ee) in short reaction time. Also, disclosed herein is “one-pot” asymmetric synthesis of biologically important natural compounds having 3-substituted chiral phthalide structural framework in the molecule.

主权项

1. Single step, asymmetric dihydroxylation (AD) and nitrile accelerated catalytic oxidative cyclization for synthesis of 3-substituted chiral phthalides of Formula II, comprising,
(a) reacting o-cyano substituted aryl alkenes of Formula I with AD-mix-β in presence of a solvent at room temperature ranging between 25-35° C. for a period ranging between 3-7 h to form a cyclic amino ether (b) hydrolyzing the cyclic amino ether with water to form the lactone of Formula II; wherein AD-mix-β comprises potassium osmate K2OsO2(OH)4; potassium ferricyanide K3Fe(CN)6; potassium carbonate; and chiral ligand (DHQD)2PHAL; and wherein R1, R2, R3 and R4 are independently same or different groups selected from hydrogen, C1-C7 straight or branched alkyl, C1-C7 alkoxide, —OTs, —OBn, C6-C10 aryls, C3-C6 cycloalkyl, C3-C6 cycloalkenes, heteroaryls, —NR6R7, —CN, —CONR8R9, —CO—R10; and —COOR11; R5 is selected from hydrogen, C1-C7 straight or branched, and C2-C7 alkyl alkoxy where alkyl is C1-C3 and alkoxy is C1-C4, C6-C10 aryl, —COO R12, where R12 is C1-C4alkyl; when R5 is —COOR12, R1 and R4 is hydrogen, R2 and R3 together may represent —O—CH2—O or a phenyl ring, R12 is C1-C4alkyl; when R5 is C1-C7 straight or branched alkyl, R1 is —O-alkyl, R4 is H, R2 and R3 together represent a heteroarly.