Method for using Cu to catalyze indole to perform asymmetric Friedel-Crafts acylation reaction

Abstract

A method for using Cu to catalyze indole to perform asymmetric Friedel-Crafts acylation reaction is disclosed. Employed reaction substrates comprise an indole and a (phenylmethylene)malonate, and a catalysis system is a Cu(II)-disulfonamide diamine ligand complex. The reaction is performed under the following conditions that the temperature is in the scope of room temperature to -20 DEG C, the solvent is ethanol, methanol, isobutanol, n-propanol and other alcohol solvents, the catalytic amount is 1-10%, an employed metal precursor is copper(II) trifluoromethanesulfonate (Cu(OTf)2) or copper perchlorate (Cu(ClO4)2.6H2O), and an employed chiral ligand is a disulfonamide diamine ligand. A catalyst preparation method comprises under the protection of N2, stirring the copper metal precursor and the chiral disulfonamide diamine ligand in the alcohol solveny at room temperature for 2 hours, so as to obtain the catalyst. Asymmetric Friedel-Crafts acylation reaction can be smoothly performed on various substituted indoles and a (phenylmethylene)malonate for obtaining a corresponding chiral product. The yield is up to 99%, and the enantiomeric excess value is up to 96%.

Description

technical field [0001] The invention relates to a method for catalyzing the asymmetric Friedel-Crafts alkylation reaction of indole and benzylidene malonate by using a homogeneous system of Cu and bissulfonamide bisamine complex with high enantioselectivity. Background technique [0002] Chiral indole derivatives widely exist in some biologically active natural products and drugs[(a)Faulkner,D.J.Nat.Prod.Rep.2002,19,1.(b)Chen,F.E.;Huang,J. Chem.Rev.2005,105,4671.(c)Kam,T.S.;Choo,Y.M.J.Nat.Prod.2004,67,547.(d)Kinsman,A.C.;Kerr,M.A.J.Am.Chem.Soc.2003,125,14120. (e) Huber, U.; Moore, R.E.; Patterson, G.M.L.J. Nat. Prod. 1998, 61, 1304. (f) Eggert, U.; Diestel, R.; Sasse, F.; Jansen, R.; Kunze, B.;Kalesse,M.Angew.Chem.Int.Ed.2008,47,6478.(g)Waldmann,H.;Hu,T.S.;Renner,S.;Menninger,S.;Tannert,R.;Oda, T.;Arndt,H.D.Angew.Chem.Int.Ed.2008,47,6473.(h)Cacchi,S.;Fabrizi,G.Chem.Rev.2005,105,2873.(i)Taylor,M.S.;Jacobsen , E.N.J.Am.Chem.Soc.2004,126,10558.(j) Mattson,R.J.;Catt,J.D.;Denh...

AI Technical Summary

Problems solved by technology

Although some progress has been made in the asymmetric Friedel-Crafts reaction of indole and benzylidene malonate, the ligands developed for this reaction are limited to oxazolines and N,N’-oxide ligands.

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