Palladium-Catalyzed Environmentally Benign Acylation

Abstract

Recent trends in research have gained an orientation toward developing efficient strategies using innocuous reagents. The earlier reported transition-metal-catalyzed carbonylations involved either toxic carbon monoxide (CO) gas as carbonylating agent or functional-group-assisted ortho sp(2) C-H activation (i.e., ortho acylation) or carbonylation by activation of the carbonyl group (i.e., via the formation of enamines). Contradicting these methods, here we describe an environmentally benign process, [Pd]-catalyzed direct carbonylation starting from simple and commercially available iodo arenes and aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct coupling of iodoarenes with aldehydes without activation of the carbonyl and also without directing group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide and pitofenone.

Palladium Catalyzed Direct Acylation of Iodo‐Acetanilides/Iodo‐Phenyl Acetates: Domino One‐Pot Synthesis of 2‐Quinolinones

“…In this Pd-catalysis, iodoarenes underwent direct coupling with inactivated aldehydes. [9] Significantly, unlike earlier reports, the reaction was feasible without activating the aldehyde functionality. Consequently, a domino one-pot synthesis of indenones by using Pd-catalyzed direct acylation and intramolecular aldol condensation sequence was reported.…”

“…), tert‐butyl hydroperoxide (TBHP) in H 2 O (5 equiv. ), 120 °C, 12 h}] . Gratifyingly, the reaction was amenable and gave corresponding ortho ‐acylacetanilide 3aa in 82 % yield (Scheme ).…”

Palladium‐Catalyzed Direct Oxidative Coupling of Iodoarenes with Primary Alcohols Leading to Ketones: Application to the Synthesis of Benzofuranones and Indenones

“…Extending our investigations in transition‐metal catalysis, recently, a [Pd]‐catalyzed environmentally benign acylations was reported, for the synthesis of various ketones. [20a] Subsequently, its precision was seen in the one‐pot synthesis of indenones,[20b] 4‐aryl‐2‐quinolinone,[20c] phthalazine and phthalazinones. [20d] Herein, we describe an oxidative strategy, in which alcohols have been employed as acylating agents, under palladium‐catalyzed direct acylations.…”

“…[20a] Subsequently, its precision was seen in the one‐pot synthesis of indenones,[20b] 4‐aryl‐2‐quinolinone,[20c] phthalazine and phthalazinones. [20d] Herein, we describe an oxidative strategy, in which alcohols have been employed as acylating agents, under palladium‐catalyzed direct acylations. Alcohols are less toxic, stable, and widely available and are inexpensive compared to α‐oxocarboxylic acid and aldehydes.…”

C–H functionalisation of aldehydes using light generated, non-stabilised diazo compounds in flow

“…Formation of unsymmetrical ketones directly from aldehydes is more desirable than from activated substrates but more challenging still. Direct formyl C-H insertion to create a new sp 2 -sp 3 or sp 2 -sp 2 carbon-carbon bond is achievable via Palladium, [40][41][42][43] Rhodium, 44,45 or Nickel [46][47][48][49] catalysed processes as well as through NHC mediated organocatalysis 50,51 or indeed diazo chemistry 27,28 (Scheme 3).…”