Direct arylation regioselectivity

For the alkylation and alkenylation of C-H bonds, olefins and acetylenes are used as reactants. This type of coupling protocol is not applicable to arylation. Recently, a nitrogen-directed arylation of aromatic C-H bonds, leading to biaryl compounds has been developed. In 2001, Oi demonstrated that ruthenium(II)-phosphine can be used as a catalyst in the regioselective arylation of 2-arylpyridines using aryl halides (Eq. 9.34) [4 ]. The predominant ortho selectivity indicates that the coordination of... 

The remarkable stability of ruthenium complexes could, further, be exploited for direct arylations between simple arenes as pronucleophiles and inexpensive, broadly available phenols as proelectrophiles. Notably, this operationally simple dehydrative direct arylation was achieved with a highly chemo- and regioselective ruthenium catalyst, along with a sulfonyl chloride, and proceeded overall through the functionalizations of both C-H as well as C-OH bonds (Scheme 29) [85],... 

Consequently, ruthenium-catalyzed direct arylations with aryl halides in less coordinating apolar solvents, such as toluene, were probed. Notably, a catalytic system derived from SPO preligand 59 enabled regioselective C-H bond functionalizations at the aromatic moieties of /V-aryl substituted 1,2,3-triazoles (Scheme 32) [88],... 

Campeau L-C, Rousseaux S, Fagnou K (2005) A solution to the 2-pyridyl organometallic cross-coupling problem regioselective catalytic direct arylation of pyridine V-oxides. J Am Chem Soc 127 18020-18021... 

An elegant application of regioselective palladium-catalyzed direct arylations of anilides in the presence of stoichiometric amounts of AgOAc in trifluoroacetic acid [65] permitted the preparation of chiral diamines with varying steric demands (Scheme 9.28) [66]. 

Intermolecular direct arylations of heteroarenes with aryl halides were thus far predominantly accomplished with palladium or rhodium complexes [31, 39,75, 76], Hence rhodium catalysts proved applicable to various electron-rich heteroarenes. In contrast, less expensive and more versatile palladium catalysts allowed for direct arylations of both electron-rich and electron-deficient substrates. Generally, the problem of achieving regioselectivities in direct arylation reactions of heteroarenes is less pronounced than it is for simple arenes, since in many cases the heteroatom can be considered as an endocyclic directing group. 

C—H bond arylations of electron-deficient heteroarenes, such as azines, remain highly challenging. An elegant and versatile solution was recently elaborated, however, through a redistribution of electron density in the starting pyridine by chemical modification [77, 78]. It was found that pyridine N-oxides smoothly underwent regioselectively palladium-catalyzed direct arylations with a variety of aryl bromides (Scheme 9.36) [77a]. 

In contrast, N-methylpyrrole underwent direct arylations atthe 3-position [93], and a comparable result was obtained in direct arylations of N-phenylpyrrole employing the electron-deficient rhodium complex 114, in combination with Ag2C03 under microwave irradiation [74b]. Selected examples of regioselective arylations of substituted five-membered heteroarenes are summarized in Table 9.3. 

Direct arylations of benzo[fo]furans, benzo[b]thiophenes, and indoles displayed different regioselectivity patterns. The chemical behavior of benzo[b]furans and benzo[fo]thiophenes are rather similar to those of non-benzannelated furans and thiophenes, respectively (Table 9.4). 

Scheme 9.42 Palladium-catalyzed regioselective direct arylation of the indolizine 148...

As described above, appropriately functionalized aromatic substrates such as phenols and aromatic carbonyl compounds undergo intermolecular arylation directly and regioselectively on treatment with aryl halides in the presence of palladium catalysts. As illustrated in Scheme 3, which is a proposed general... 

Recent Advances in the C2 and C3 Regioselective Direct Arylation of Indoles... 

---