Pd(OH)₂/C, a Practical and Efficient Catalyst for the Carboxylation of Benzylic Bromides with Carbon Monoxide

Abstract

A simple, efficient, cheap, and broadly applicable system for the carboxylation of benzylic bromides with carbon monoxide and water is reported. Upon simple reaction with only 2.5 wt % of Pearlman's catalyst and 10 mol % of tetrabutylammonium bromide in tetrahydrofuran at 110°C for 4 h, a range of benzylic bromides can be smoothly converted to the corresponding arylacetic acids in good to excellent yields after simple extraction and acid−base wash. The reaction was found to be broadly applicable, scalable, and could be successfully extended to the use of ex situ-generated carbon monoxide and applied to the synthesis of the nonsteroidal anti-inflammatory drug diclofenac.

Carbon Monoxide as C1 Building Block in Fine Chemical Synthesis†

“…Echeverria and Evano [ 117 ] reported the carboxylation of benzylic bromides using CO as a tool to prepare benzylic acids. The reaction was performed using Pd(OH) 2 /C as catalyst and tetrabutylammonium bromide (TBAB) as catalyst stabilizer, in the presence of 4 equiv.…”

Copper‐Catalyzed Cross‐Coupling of Acylzirconocenes and Diaryliodonium Salts: An Efficient Synthesis of Alkyl‐aryl‐ketones from Alkenes

“…This issue was however efficiently addressed by the Skrydstrup group who designed a set of efficient and safe procedures for the in situ generation of carbon monoxide in a two-chamber system. [15] This, combined with our joint interests in copper catalysis [16,17] and carbonylation chemistry, [18] prompted us to investigate this procedure for the safe generation of acylzirconocenes 2 from alkenes 1 and their use in copper-catalyzed cross-coupling with diaryliodonium salts [19,20] 4, which would, in addition to further expend the usefulness of acylzirconocenes in synthesis, provide an efficient entry to alkyl-aryl-ketones 5 from readily available alkenes as starting materials (Figure 1, bottom).…”

Selective Photochemical Continuous Flow Benzylic Monochlorination

“…Benzylic halogenation is arguably one of the key transformations in organic chemistry illustrated by the Wohl–Ziegler reaction . Due to the ubiquity and versatility of the obtained halogeno derivatives, these latter ones can be involved in a variety of reactions and, among them, nucleophilic substitutions and metal-catalyzed reactions, allowing the access to key intermediates. The preparation of benzylic chlorides and bromides, starting from the corresponding tolyl derivatives, has been widely studied over the past few decades.…”