Chemoselective Pd‐Catalyzed Isocyanide Insertion Reaction of Enaminones by C–H Functionalization: Hydrolysis or Cyclization through 1,3‐Palladium Migration

Abstract

A chemoselective palladium-catalyzed isocyanide insertion reaction of enaminones was developed. Amide derivatives were synthesized by this C-H functionalization and subse-[a] Key 4699 quent hydrolysis reactions. 4-Aminoquinoline derivatives were prepared by this C-H functionalization, which includes a 1,3-palladium migration in the process.With the optimal conditions in hand, we explored the reactions of enaminones 1 with 2a (Table 2). For enaminones that have an unsubstituted or o-Me-substituted aryl www.eurjoc.org

Facile Coupling of Aldehydes with Alcohols: An Evolved Tishchenko Process for the Preparation of Unsymmetrical Esters

“…Another proposed change involves the addition of a ketone to the reaction to serve as a hydride acceptor in the six-membered transition state (see be- . The ketones will be reduced into secondary alcohols, [17,18,38,39] and given our previous results that show the inferior nucleophilicity of secondary alcohols compared with primary alcohols, most of the ketone will remain unreacted in the reaction mixture. Therefore, using the appropriate ketone should suppress the Tishchenko cycle and allow the reaction to proceed selectively towards the unsymmetrical ester [Scheme 2 Equation (2)].…”

Recent Advances in Palladium-Catalyzed Isocyanide Insertions

“…Interestingly, a substrate-dependent chemoselective transformation with N -arylenaminones 311 was communicated by Luo et al ( Scheme 84 ) [ 135 ]. Tertiary aliphatic isocyanides afford the carboxamides 313 via hydroxyimidoylation, which was later corroborated by Luo et al [ 136 ] However, the use of aromatic isocyanides lead to the tacrine derivatives 312 ( Scheme 84 ).…”

Recent advances in transition metal migration involving reactions

“…In 2015, a 1,3-palladium migration involved novel synthetic methodology for preparing 4-aminoquinoline derivatives 67 was reported by the Wang and Ji group (Scheme 15). 13 This protocol employed diverse enaminones 65 and isocyanides 66 as the reaction substrates to give the corresponding products in moderate yields, while the annulation did not take place with enaminones bearing a strong electron-withdrawing group in the benzene ring, such as nitro. On the basis of exploration experiments, a plausible reaction mechanism was proposed for this 1,3-migration process (Scheme 16).…”