Method for using Cu to catalyze indole to perform asymmetric Friedel-Crafts acylation reaction
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A Friedel-Crafts alkylation and asymmetric technology, applied in the field of Cu-catalyzed asymmetric Friedel-Crafts alkylation of indole, to achieve the effects of simple synthesis, easy availability of raw materials, and simple synthesis of chiral ligands
Inactive Publication Date: 2014-10-29
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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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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Embodiment 1
[0026] Example 1: Synthesis of indole derivatives 3 by Cu-catalyzed asymmetric Friedel-Crafts alkylation reaction
[0027] Put copper salt metal precursors into the reaction bottle: copper trifluoromethanesulfonate (0.0125 mmol) and chiral ligand L1 (0.0125 mmol), add 1 ml of i-BuOH solvent after nitrogen replacement, and stir at room temperature for 2 h , placed in a cold bath at 0°C, added substrate 2 (74.5 mg, 0.3 mmol) and stirred for 10 minutes, then added substrate 1 (29.3 mg, 0.25 mmol), reacted at room temperature, and TLC detected that substrate 1 was completely The disappearance means that the reaction is complete, and the reaction is about 2-12 hours, and the reaction solvent is drained with an oil pump. Then, column chromatographic separation afforded the pure product. The reaction formula is as follows:
[0028]
[0029](S)-Ethyl2-ethoxycarbonyl-3-(3-indolyl)-3-phenyl propanoate(3a).99%yield,95%ee,[α] 20 D =+63.4(c1.0,CH 2 Cl 2 ); 1 H NMR (400MHz, CDCl ...
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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...
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