Boronic copper-catalyzed arylations

In addition to Ullmann s copper-catalyzed [107] C(spVN bond formations using haloarenes, a remarkable complementary approach was developed by Chan and Lam during the 1990s using boron-based arylating reagents [108, 109). A detailed review by Andrew W. Thomas and Steven V. Ley on these oxidative copper-mediated and copper-catalyzed arylations, as well as their extension to alcohols [108, 110], is to be found in Chapter 4. 

Copper-Catalyzed Arylations of Amines and Alcohols with Boron-Based Arylating Reagents... 

Scheme 4.12 Copper-catalyzed arylations of aryl boronic acids using carboxylic acid additives.

Savarin, C., SrogI, J., Liebeskind, L. S. A Mild, Nonbasic Synthesis of Thioethers. The Copper-Catalyzed Coupling of Boronic Acids with N-Thio(alkyl, aryl, heteroaryl)imides. Org. Lett. 2002,4, 4309-4312. 

The a,(3-unsaturated ester (8), aldehyde (9), and nitro (10) compounds participate as electrophiles in a number of useful conjugate addition reactions. Copper-catalyzed addition of Grignard reagents provides access to aryl butanoic acid derivatives substituted with an oxetane (equation 1 in scheme 13.7). The ester, aldehyde, and nitro electrophiles also undergo mild Rh-catalyzed additions of aryl and vinyl boronic acids (equation 2 through equation 4 in scheme 13.7). Interestingly, the unsaturated aldehyde participates readily in an amine conjugate addition to afford oxetane substituted 3-amino-acetaldehyde derivatives. 

This chapter will attempt to summarize selected key learnings and trends, and will also highlight recent developments of these methods solely devoted to the copper-catalyzed oxidative arylations of O—H and N—H bonds with boron-based arylating reagents. Further, it will detail some specifics that have brought the method to its current high levels of popularity within the synthetic organic chemistry community. 

Scheme 4.2 Plausible mechanism for copper-catalyzed crosscouplings of aryl boronic acids with phenols.

Scheme 4.9 First copper-catalyzed N—H bond arylation with boronic acids.

Interestingly, in contrast to the numerous intramolecular couplings between alcohols and aryl boronic acids [lb], there are no reports of intramolecular copper-catalyzed N—H bond arylahons with boronic acids. 

On an industrial scale (100+ kg), perampanel can be prepared in six linear steps in a 24% overall yield. Addition of bromine to a solution of 2-methoxypyridine 23 cleanly afforded 5-bromo-2-methoxypyridine 24 in 86% yield. The 5-pyridyl moiety was introduced via a metal-halogen exchange on bromide 24 followed by addition to 2-(phenylsulfonyl)pyridine versus the biaryl couplings found in earlier routes. Acid hydrolysis of 25 gave pyridinone 26, which underwent a copper-catalyzed V-aryl coupling to afford pyridinone 27 in 83% yield. NBS bromination smoothly provided the bromo pyridinone 28, which was coupled with boronate 29 to give perampanel (1). 

Liu T, Shen Q (2011) Copper-catalyzed trifluoromethylatimi of aryl and vinyl boronic acids with an electrophilic trifluoromethylating reagent. Org Lett 13 2342-2345. doi 10.1021/ O12005903... 

With Copper In 2008, Basle and Li reported [107] a copper-catalyzed oxidative sp C-H bond arylation with aryl boronic acids (Scheme 4.19). This method provides access to biologically active tetrahy-droisoquinoline products. Either peroxide or molecular oxygen can be used as the oxidant. On using PhPyBox ligand, an enantioselectivity as high as 44% ee using CuOTf was obtained. 

The Ir catalyst [Ir(COD)OMe]2 was successfully exploited for the borylation of arenes under microwave conditions, this was then followed by the in situ copper-catalyzed sulfenylation of the intermediate aryl boronate to the aryl thioether product using an arylthiol, with microwave conditions [118]. 

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