Decarboxylative cross-coupling

A significant advantage of this reaction is that it uses relatively inexpensive carboxylic acids (or their salts) and is far less air and moisture sensitive in comparison to typical cross-coupling organometallic reagents.

Furthermore, the carboxylic acid moiety is a common feature of natural products and can also be prepared by relatively benign air oxidations.

Thermal decarboxylation of copper benzoates, in the presence of an aryl halide, was found to produce (both symmetric and unsymmetric) biaryls through aryl-Cu intermediates.

[2] This monometallic copper system required drastic conditions for complete cross-coupling, and had various intrinsic limitations, both of which prevented development of a catalytic, preparatory version of this reaction.

[4] A Pd–Cu bimetallic system was not discovered until 2006 when Goossen et al. reported a decarboxylative cross-coupling of aryl halides with ortho-substituted aromatic carboxylic acids.

[14] Through subsequent studies it was found that the use of aryl triflates allowed substrate scope for cross-coupling to be extended to some aromatic carboxylates lacking any ortho-substitution (less reactive).

[3] As well, the variability of this combined catalytic system allows for promotion of a large spectrum of reactions, including aryl ketone formation, c-heteroatom cross-coupling, and many others.

[3][18] The product scope of this reaction is extremely broad with the use of different substrates; however development of different functionalities has required accompanied studies to determine the proper catalyst system.

[1] Per IUPAC, the term biaryl refers to an assembly of two aromatic rings joined by a single bond,[19] starting with the simplest, biphenyl.

Biaryls constitute an important structural motif of physical organic, synthetic, and catalytic interest—for instance, underlying the area of atropisomers in enantioselective synthesis—and they appear in many pharmaceutical, agrochemical, and materials (e.g. LCD) applications.

[21] [22] [23] [24] Further work by Goossen et al. described the synthesis of ketones from α-oxocarboxylic acids with aryl or heteroaryl bromides through an acyl anion intermediate.

One such reaction by Shang et al. described a palladium catalyzed cross coupling that enables the formation of functionalized pyridines, pyrazines, quinolines, benzothiazoles, and benzoxazoles.

[26] Miura et al. reported the cross coupling of vinyl bromides with an alkenyl carboxylic acid using a palladium catalyst.

[30] Liu et al. reported the C-S coupling of aryl carboxylic acids with disulphides or thiols using a Pd/Cu catalyst system.

This proton is abstracted by silver carbonate, which acts as both a base and an oxidant to regenerate the starting palladium complex completing the catalytic cycle.

Forgione, P., Bilodeau, F. et al. reported that heteroatoms containing a carboxylic acid also are tolerated by palladium monometallic systems and undergo decarboxylative cross coupling with aryl halides.

Decarboxylative cross-coupling general reaction scheme
Decarboxylative cross-coupling general reaction scheme
First reported decarboxylative Ullmann coupling (Nilsson, 2005)
First reported decarboxylative Ullmann coupling (Nilsson, 2005)
Copper catalyzed decarboxylative biaryl synthesis reported by Goossen et al.
Cu-catalyzed decarboxylative coupling of amino acids, reported by Jiang et al.
Pd-catalyzed Heck olefination, reported by Myers et al.
Pd-catalyzed decarboxylative cross-coupling of aryl halides with potassium cyanoacetate, reported by Yeung et al.
Decarboxylative cross-coupling of potassium polyfluorobenzoates, reported by Shang et al.
Biaryl synthesis using a Cu–Pd catalyst system, reported by Shang et al.
Decarboxylative cross-coupling of aryl triflates with aryl carboxylates using a Pd–Ag catalyst system, reported by Goossen et al.
Formation of Biaryls (Goossen et al. (2007))
Formation of Biaryls (Goossen et al. (2007))
Formation of Aryl Alkynes (Zhao et al. (2010))
Formation of Aryl Alkynes (Zhao et al. (2010))
Formation of Aryl Ketones (Goossen et al. (2008))
Formation of Aryl Ketones (Goossen et al. (2008))
Formation of Aryl Esters (Shang et al. (2009))
Formation of Aryl Esters (Shang et al. (2009))
Formation of sp3C-heteroaromatics by Shang et al. 2010
Formation of sp3C-heteroaromatics by Shang et al. 2010
Formation of conjugated dienes (Miura et al. (2010))
Formation of conjugated dienes (Miura et al. (2010))
Formation of olefins by Hu et al. (Hu et al. (2009))
Formation of olefins by Hu et al. (Hu et al. (2009))
Formation of phenanthrene derivatives by Wang et al. (Wang et al. (2010))
Formation of phenanthrene derivatives by Wang et al. (Wang et al. (2010))
C-N cross-coupling by Jiao et al. (Jiao et al. (2010))
C-N cross-coupling by Jiao et al. (Jiao et al. (2010))
C-S cross-coupling by Liu et al. (Liu et al. (2009))
C-S cross-coupling by Liu et al. (Liu et al. (2009))
C-P cross-coupling by Yang et al. (Yang et al. (2011))
C-P cross-coupling by Yang et al. (Yang et al. (2011))
C-X cross-coupling by Wu et al. 2010
C-X cross-coupling by Wu et al. 2010
by Meyers et al. 2005
by Meyers et al. 2005
Decarboxylative biaryl synthesis mechanism, Goossen et al. 2006
Decarboxylative biaryl synthesis mechanism, Goossen et al. 2006
Proposed mechanism of heteroaromatic acid coupling, Forgione et al. 2006
Proposed mechanism of heteroaromatic acid coupling, Forgione et al. 2006