An efficient Friedel-Crafts reaction of a series of 2-substituted thiophenes with alkyl glyoxylates has been developed using a catalytic amount of an easy accessible 6,6'-dibromo-BINOL/Ti(IV) complex. A variety of hydroxy(thiophene-2-yl)acetates can be synthesized in high enantioselectivites (92-98% ee) and good yields. This is the first report on the efficient asymmetric F-C reaction of thiophenes with alkyl glyoxylates. Starting from simple thiophene and n-butyl glyoxylate, we demonstrated the formal synthesis of duloxetine.