A General, Activator‐Free Palladium‐Catalyzed Synthesis of Arylacetic and Benzoic Acids from Formic Acid

Abstract

A new catalyst for the carboxylative synthesis of arylacetic and benzoic acids using formic acid (HCOOH) as the CO surrogate was developed. In an improvement over previous work, CO is generated in situ without the need for any additional activators. Key to success was the use of a specific system consisting of palladium acetate and 1,2‐bis((tert‐butyl(2‐pyridinyl)phosphinyl)methyl)benzene. The generality of this method is demonstrated by the synthesis of more than 30 carboxylic acids, including non‐steroidal anti‐inflammatory drugs (NSAIDs), under mild conditions in good yields.

Alkali-modified heterogeneous Pd-catalyzed synthesis of acids, amides and esters from aryl halides using formic acid as the CO precursor

“…Additionally, to demonstrate the versatility of this novel catalyst under the optimized reaction conditions, we validated the possibility of using different nucleophiles to investigate these alkyl group's effects on the alcohol for the alkoxycarbonylation reaction. Notably, methanol was the most efficient nucleophile compared to the others, though, no signicant difference in product yields and selectivities (Table 2, entries [13][14][15][16][17][18]. The observation thus implies that an increase in the alkyl chain length on the alcohols may substantially reduce yields owing to the formation of additional side products.…”

“…To address this issue on a laboratory scale, much emphasis has been directed towards the use of CO surrogates. 7,[8][9][10] Numerous surrogates, including aldehydes, 11 formic acids, 7,[12][13][14][15] and formates, 16,17 have been used in carbonylation processes catalyzed by transition metals. Among these CO substitutes, formic acid (HCOOH) is the most practical surrogate since it can be readily obtained via CO 2 hydrogenation 18,19 and bio-waste fermentation.…”

Recent Advances in Metal‐Catalyzed Carbonylation Reactions by Using Formic Acid as CO Surrogate

“…Later on, Lin Wang and group reported an activator free strategy for the synthesis of arylacetic acid and benzoic acid (Scheme ) . This strategy involves insitu generation of CO form HCOOH without any utilization of activator along with the use of Pd(OAc) 2 as a catalyst.…”