Palladium-catalyzed oxidative cross-coupling

Oxidative Cross-Coupiing Reactions C(sp )-organozincs can also take part in palladium-catalyzed oxidative cross-coupling reactions. C(sp )-C(sp) couplings, not easy to achieve by more classical approaches involving haloalkynes, are readily performed. 

The groups of Hu and You reported a remarkable palladium-catalyzed oxidative cross-coupling of Af-containing heteroarenes 62 with diversely substituted thiophenes 47 to afford products 63A-D (Scheme 10.19). The Af-containing heteroarenes included electron-rich heterocycles such as xanthines and azoles as weU as electron-poor heterocycles such as pyridine IV-oxides. In cases where heteroarenes demonstrated sluggish reactivity, CuBr was used as an additive to assist C—H bond activation. A computational study provided support for a two-fold C—H activation pathway via a CMD mechanism. 

Hull KL, Sanford MS (2009) Mechanism of benzoquinone-promoted palladium-catalyzed oxidative cross-coupling reactions. J Am Chem Soc 131 9651—9653... 

Gong X, Song G, Zhang H, Li X (2011) Palladium-catalyzed oxidative cross-coupling between pyridine and A-oxides and indoles. Org Lett 13 1766-1769... 

Basu et al. have reported palladium-catalyzed selective cross coupling of bromo-pyridines and amines on the surface of potassium fluoride supported basic aluminium oxide [5]. For example, amination of 2,6-dibromopyridine by this method afforded the monoaminated products predominantly, even after prolonged the reaction time and using excess amine, whereas previous method [6] gave only bis-aminated products (Scheme 5.3). 

Scheme 5.3 Palladium-catalyzed selective cross coupling of bromopyridines and amines on potassium fluoride supported basic aluminium oxide.

This oxidative cross-coupling was reminiscent of the Scholl reaction and of the work of van Helden, Verberg, Itahara, and Fujiwara, who used stoichiometric Pd(II) salts for the synthesis of biaryls and styrenes. At the time that we were acquiring these data, mie example of a palladium-catalyzed oxidative cross-coupUng had was reported for the synthesis of a biaryl (the synthesis of 1-phenylnapthalene), so we decided to explore this new chemical territory. 

I am grateful to his former postdoctoral researcher. Dr. David Stuart, for accepting the task of writing Keith s chapter on the discovery and development of a palladium(ll)-catalyzed oxidative cross-coupling of two unactivated arenes. 

While the nickel-catalyzed reaction facilitates oxidative addition of substrates problematic to palladium-mediated processes, there is still a great deal of interest in the palladium-catalyzed Kumada cross-coupling reaction due to its enhanced chemoselectivity. Also, as mentioned previously, one distinct advantage of the palladium-catalyzed procedure, is that it allows versatile organolithium reagents to be used as an alternative to Grignard... 

The intramolecular version of palladium-catalyzed decarboxylative cross-coupling reaction of aromatic carboxylic acids with organic halides also worked well. For example, 2-bromophenyl-tethered benzoic acids 116 underwent cyclization in the presence of Pd(OAc)2/PPh3 and K2CO3 in NMP to give 117 in high yields (Scheme 22.27) [51]. A mechanism that involved a sequence of oxidative addition, cyclization of carboxylate 118, decarboxylation of 119, and reductive elimination was proposed. Indole-2-carboxylic acid 121 was also applicable to this type of cyclization. 

Cationic palladium-catalyzed addition of arylboronic acids to nitriles for the formation of benzo[h]furans was reported <06OL5987>, an example of which is illustrated in the following scheme. The palladium-catalyzed cross coupling of alkynes with appropriately substituted aryl iodides for the synthesis of substituted dibenzofurans in moderate to excellent yields was also achieved <06JOC5341>. The benzo[fc]furan core of heliannuls G and H were constructed by a palladium-catalyzed Ji-allyl cyclization reaction <06TL7353>. The palladium-catalyzed oxidative activation of arylcyclopropanes was applied to the synthesis of 2-substituted benzo[Z>]furans <06OL5829>. 

Although not directly relevant to this review, it should be noted that Sanford, Shi and Buchwald have also reported a palladium-catalyzed reaction for the chemo-and regioselective oxidative cross-coupling between ligand coordinated L-Cat-H substrates and simple arenes (Ar-H) [55-57]. 

Stuart DR, Villemure E, Fagnou K (2007) Elements of regiocontrol in palladium-catalyzed oxidative arene cross-coupling. J Am Chem Soc 129 12072-12073... 

Recent work has led to the use of bulk electron-rich phosphine ligands to facilitate palladium-catalyzed processes with problematic oxidative addition. For examples, see (a) Littke, A.F. Fu, G.C. A convenient and general method for Pd-catalyzed Suzuki cross-couplings of aryl chlorides and arylboronic acids. Angew. Chem., Int. Ed. Engl. 1998, 37, 3387-3388. (b) Shen, W. Palladium catalyzed coupling of aryl chlorides with arylboronic acids. Tetrahedron Eett. 1997, 38, 5575-5578. (c) Old, D.W. Wolfe,... 

A palladium-catalyzed oxidative C—H/C—H cross-coupling between benzothiazoles 70 and thiazoles 71 is carried out under base-free conditions (14CC3996).This reaction appears to be insensitive to air and moisture and displays high-functional group tolerance. 

Controlling site selectivity in palladium-catalyzed oxidative crosscoupling of AryEH with benzo[/i]quinoline 12ACR936. Haloquinolines as substrates for Pd-catalyzed cross-coupling reactions to afford substituted quinolines 13JHC1. 

For synthesis of quinazoline derivatives, various coupling reactions have been utilized after synthesis of quinazoline-2,4(lH,3H)-diones via palladium-catalyzed oxidative coupling by Hirota et aL [187]. For example, synthesis of diarylquinazolines by iron-catalyzed cross-coupling reaction [188], and diamino quinazolinones by palladium-catalyzed amination [171] have been developed Synthetic applications to quinazoline alkaloids are given in Sect. 3. 

Suzuki and colleagues described the first palladium-catalyzed oxidative carbonylation of alkenylboranes as early as 1981. They prepared 1-alkenylboranes by hydroboration of alkynes and subsequent oxidative carbonylation mediated by a catalytic amount of PdCL, in the presence of NaOAc and BQ in methanol, which provided unsaturated esters in good yields (Scheme 8.27a) [106]. Later, a stereoselective synthesis of ]S-mono- and / , / -disubstituted a, ]S-unsaturated esters was established by a stepwise cross-coupling alkylation followed by an oxidative carbonylation of 2-bromo-1-alkenylboranes (Scheme 8.27b) [107]. Good yield and excellent stereoselectivity was achieved. 

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