Catalytic and Stoichiometric Synthesis of Novel 3‐Aminocarbonyl‐, 3‐Alkoxycarbonyl‐, and 3‐Amino‐4‐indolylmaleimides

Abstract

Novel nonsymmetrically substituted 4‐indolylmaleimides have been synthesized via palladium‐catalyzed alkoxy‐ and aminocarbonylation of 3‐bromo‐1‐methyl‐4‐(2‐methyl‐3‐indolyl)maleimide (1) with alcohols and amines in the presence of carbon monoxide. The resulting carboxamide derivatives represent a new class of potentially bioactive compounds. In addition, the direct amination reaction of 1 proceeded smoothly in the absence of catalyst and gave the desired 3‐amino‐4‐indolylmaleimides in good yields.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Palladium‐Catalyzed Carbonylation Reactions of Aryl Halides and Related Compounds

“…Most recently, this catalyst system was applied to synthesize potentially bioactive 3-alkoxycarbonyland 3-aminocarbonyl-4-indolylmaleimides from 3-bromoindolylmaleimide 26 (Scheme 11). [35] Cacchi and et al developed a protocol for the hydroxycarbonylation of aryl and vinyl halides or triflates in which a combination of acetic anhydride and lithium formate was used as a condensed source of carbon monoxide. [36] The transformations tolerated a wide range of functional groups, including ether, ketone, ester, and nitro groups.…”

Metal-Catalyzed Cross-Coupling Reactions of Halomaleic Anhydrides and Halomaleimides: Synthesis of Structurally Interesting and Biologically ­Important Natural and Unnatural Products

“…Beller and co-workers successfully carbonylated 2-bromo-N-methyl-3-(2-methyl-1H-indol-3-yl)maleimide (42) using carbon monoxide with amines or alcohols in the presence of Pd(OAc) 2 /di-1-adamantyl(butyl)phosphine (cataCXium ® A). 20 The resulting 2-(aminocarbonyl)-and 2-(alkoxycarbonyl)-3-indolylmaleimides 44 were obtained in 25-70% yields (Scheme 18). This approach provides a nice pathway for carbonyl insertion and scope to build new heterocyclic systems for structure-activity relationship studies.…”

Palladiumkatalysierte Carbonylierungen von Arylhalogeniden und ähnlichen Substraten

“…34 Anders als bei den meisten Carbonylierungsverfahren genügten schon vergleichsweise geringe Katalysatormengen (<0.5 Mol‐% Pd), um die gewünschten Produkte unter 5 bar Kohlenmonoxid in ausgezeichneten Ausbeuten zu erhalten. Kürzlich wurde dieses Katalysatorsystem zur Synthese potenziell biologisch aktiver 3‐Alkoxycarbonyl‐ und 3‐Aminocarbonyl‐4‐indolylmaleimide aus dem 3‐Bromindolylmaleimid 26 angewendet (Schema ) 35…”