Highly enantioselective Friedel-Crafts reaction of thiophenes with glyoxylates: formal synthesis of duloxetine.
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.
Majer
Jakub
J
Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland.
Kwiatkowski
Piotr
P
Jurczak
Janusz
J
D000085:Acetates / Q000737:chemistry; D000068736:Duloxetine Hydrochloride; D006038:Glyoxylates / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry*
D000085:Acetates; D006038:Glyoxylates; D009942:Organometallic Compounds; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride