Palladium-Catalyzed, Modular Synthesis of Highly Functionalized Indoles and Tryptophans by Direct Annulation of Substituted o-Haloanilines and Aldehydes

One-pot synthesis of indoles by a palladium-catalyzed annulation of o-haloanilines and aldehydes has been developed. Coupling of o-iodoaniline with aldehyde is realized under mild ligandless conditions [Pd(OAc)2, DABCO, DMF, 85 DegC], whereas X-Phos is found to be the ligand of choice for coupling reactions involving o-chloroanilines/o-bromoanilines and aldehydes. A variety of o-haloanilines with different electronic properties are suitable substrates, and aldehydes including chiral ones participated in this reaction without racemization. Coupling of (S)-2-N,N-di-tert-butoxycarbonyl-5-oxopentanoate, derived from L-glutamic acid, with o-haloanilines provides a rapid access to the ring-A-substituted tryptophans in good to excellent yields. [on SciFinder (R)]


Published in:
Journal of Organic Chemistry, 71, 20, 7826-7834
Year:
2006
Keywords:
Note:
CAN 145:471339
27-11
Heterocyclic Compounds (One Hetero Atom)
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
0022-3263
written in English.
3375-31-3; 32005-36-0; 251320-86-2; 564483-18-7 (X-Phos) Role: CAT (Catalyst use), USES (Uses) (palladium-catalyzed modular synthesis of highly functionalized indoles and tryptophans by direct annulation of substituted o-haloanilines and aldehydes); 87-63-8 (2-Chloro-6-methylaniline); 95-51-2 (2-Chloroaniline); 104-53-0 (3-Phenylpropanal); 122-78-1 (Phenylacetaldehyde); 124-13-0 (Octanal); 583-68-6 (4-Methyl-2-bromoaniline); 615-36-1 (2-Bromoaniline); 615-43-0 (2-Iodoaniline); 1003-98-1; 2401-24-3 (2-Chloro-5-methoxyaniline); 4221-03-8 (5-Hydroxypentanal); 5459-50-7 (2-Iodo-5-nitroaniline); 5949-05-3 ((S)-Citronellal); 6293-83-0 (2-Iodo-4-nitroaniline); 6828-35-9; 10403-47-1; 20896-27-9; 57056-93-6 (N-Methyl-2-iodoaniline); 72086-72-7; 91394-63-7; 98991-09-4 (2-Iodo-3-methoxyaniline); 105752-11-2; 116632-14-5; 121667-78-5 (3-(3,4,5-Trimethoxyphenyl)propanal); 139115-75-6; 153898-63-6 (2-Iodo-5-methoxyaniline); 191348-14-8 (2-Iodo-4-methoxyaniline); 192314-71-9; 354574-31-5 (2-Iodo-6-methoxyaniline) Role: RCT (Reactant), RACT (Reactant or reagent) (palladium-catalyzed modular synthesis of highly functionalized indoles and tryptophans by direct annulation of substituted o-haloanilines and aldehydes); 188200-04-6P; 188200-05-7P; 440673-79-0P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (palladium-catalyzed modular synthesis of highly functionalized indoles and tryptophans by direct annulation of substituted o-haloanilines and aldehydes); 127-08-2 (Potassium acetate); 280-57-9 (DABCO); 131274-22-1 Role: RGT (Reagent), RACT (Reactant or reagent) (palladium-catalyzed modular synthesis of highly functionalized indoles and tryptophans by direct annulation of substituted o-haloanilines and aldehydes); 1504-16-1P; 3569-21-9P (1H-Indole-3-propanol); 16886-10-5P; 24486-66-6P; 33900-28-6P; 52604-06-5P; 67960-32-1P; 870564-22-0P; 870564-23-1P; 870564-24-2P; 870564-25-3P; 896462-55-8P; 913716-14-0P; 913716-15-1P; 913716-16-2P; 913716-17-3P; 913716-18-4P; 913716-19-5P; 913716-20-8P; 913716-21-9P; 913716-22-0P; 913716-23-1P; 913716-24-2P; 913716-25-3P; 913716-26-4P; 913716-27-5P; 913716-28-6P Role: SPN (Synthetic preparation), PREP (Preparation) (palladium-catalyzed modular synthesis of highly functionalized indoles and tryptophans by direct annulation of substituted o-haloanilines and aldehydes)
Laboratories:




 Record created 2010-11-25, last modified 2018-03-17


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