Enantioselective Friedel-Crafts Alkylation of Indoles with (E)-1-Aryl-4-benzyloxybut-2-en-1-ones Catalyzed by an (R)-3,3-Br2BINOLate-Hafnium(IV) Complex

A highly enantioselective Friedel–Crafts reaction of unprotected indoles with (E)-1-aryl-4-benzyloxybut-2-en-1-ones catalyzed by a new chiral [Hf{(R)-3,3′-Br2-BINOL}(OtBu)2]2 complex has been developed to functionalize the C-3 position of the indole nucleus with a side chain bearing a 1,4-difunctionalized moiety and a benzylic stereogenic center. The reaction proceeds in good to excellent yields and excellent enantioselectivities (up to 97 % ee). The usefulness of this approach was illustrated with the synthesis of a tryptophol derivativeFinancial support from the Ministerio de Ciencia e Innovacion, Gobierno de Espana and FEDER, European Union (Grant CTQ 2009-13083) and the Generalitat Valenciana (Grants ACOMP/2012/212 and ISIC 2012/001) is acknowledged. C.V. thanks the Generalitat Valenciana for a predoctoral grant.Muñoz Roca, MDC. (2013). 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