The Barbier–Grignard-type arylation of aldehydes using unactivated aryl iodides in water

Abstract

Carbon-carbon bond formation is the essence of organic synthesis. One of the most important methods for forming carbon-carbon bonds is the Barbier-Grignard-type reaction, which was discovered over a century ago. However, it is still highly desirable to further improve this process. In this article, we describe a Barbier-Grignard-type direct arylation of aldehydes by using unactivated iodides mediated by zinc and catalysed by rhodium in water. This method bypasses a number of challenges encountered by the conventional BarbierGrignard reaction, such as strict exclusion of moisture and air, protection-deprotection of various acidic hydrogens in the substrates, and so forth. It thereby creates a safer, more convenient and more environmentally benign strategy to access the diarylmethanols and aryl alkyl alcohols, ubiquitous skeletons found in fine chemicals, biologically active molecules and pharmaceuticals. Importantly, the same reaction performed in an organic solvent proceeded sluggishly to give much inferior yields.

The introduction of the Barbier reaction into polymer chemistry

“…It is worth mentioning that PTPM-1 is a special type of stimuli-responsive polymer in the area of dual thermo-responsive polymers (based on luminescence and turbidity) over a wide temperature range, and a special type of AIE polymer without any AIE moieties. The many advantages of using the Barbier reaction in polymer synthesis are as follows: its potential tolerance to functional groups, moisture and solvents; 19 – 21 the polymer is potentially degradable due to the reversibility of Barbier reaction; there is a wide range of monomers suitable for Barbier polyaddition; the outstanding AIE and thermo-responsive luminescent properties of Barbier polymer varying over a wide temperature range; and the potential sensory, luminescence enhancement of fluorescent dyes in solid state and processing properties of Barbier polymer. The introduction of Barbier polyaddition expands the libraries of monomer and polymer in a way that opens an avenue in the design and application of functional polymer materials with both academic and economic perspectives.…”

Exploration of new reaction tools for late-stage functionalization of complex chemicals

“…[26][27][28][29][30][31][32] Previously, our group reported the successful allylation, [34][35] allenylation, 36 propargylation, 36 alkynylation, 37, 38 phenylation 39 and alkylation 40 of carbonyl or imine compounds mediated by various metals in water. Recently, as the last and most difficult challenge towards Grignard-type reactions in aqueous media, we developed a direct arylation of aldehydes using unactivated aryl iodides in water 41 (Scheme 2). This breakthrough has successfully achieved the transition from the conventional two-step anhydrous conditions to a one-pot Rh-catalyzed reaction in water.…”

Nucleophilic arylation with tetraarylphosphonium salts

“…However, this approach often suffers from narrow substrate scope, or the high moisture sensitivity and the strong basicity of the reagents. Transition-metal-catalysed arylation of carbonyl or imino groups with aryl halides 12 13 , arylboronic acid derivatives 14 15 16 17 18 19 20 or other reactive reagents 21 22 23 24 25 showed good functional group tolerance under mild reaction conditions. However, the high cost of noble transition metal complexes and possible contamination of the end products by trace amounts of heavy metals probably limit the wide application of this approach in industrial and pharmaceutical processes.…”