Arylation, Suzuki

The Suzuki aryl-aryl cross-coupling method, adapted to polymers by Schliiter, Wegner and co-workers, made it possible to synthesize solubilized PPPs 6 with a dramatically increased molecular weight (number average up to 100 1,4-phen-ylene units) [17]. 

Deprotonation of 3-fluorotoluene 53 with n-BuLi-KOr-Bu or, better, r-BuLi-KOr-Bu follows the selectivity expected with these superbases and leads to metallation at the least hindered position ortho to the fluoro substituent. Trapping the metallated intermediate 54 with dimethylfluoroboronate gave, after hydrolysis, a boronic acid whose Suzuki arylation provided the biaryl 55. These four steps may be carried out in a single pot, giving 55 in 79% overall yield from 53. 

In 1995, Queguiner reported a new route to antihypertensive 5,6-diarylpyridazin-3(2//)-ones starting from 4-acetyl-6-chloro-5-iodo-3-methoxypyridazine (79) [34]. 79 was synthesized of 79 from 6-chloro-4-(l-hydroxyethyl)-5-iodo-3-methoxypyridazine (37) by oxidation with Mn02 or PCC. The new route involves a chemoselective Suzuki arylation of a C—I over a C—Cl bond on a pyridazine nucleus. In a first Suzuki reaction, C-5 selective arylation of 79 could be obtained using only a slight excess of arylboronic acid. Subsequently, the obtained 4-acetyl-5-aryl-6-chloro-3-methoxypyridazines (80) were transformed into unsymmetrically arylated 4-acetyl-5,6-diaryl-3-methoxypyridazines (81) via a second Suzuki reaction. For this second arylation, an excess of arylboronic acid (2 equivalents) was used. By using 4 equivalents of 4-chlorophenylboronic acid on 79 symmetrically arylated 4-acetyl-5,6-bis(4-chlorophenyl)-3-methoxypyridazine was obtained in 85% isolated yield. 

Interestingly, when searching for new endogenous bioamine-interfering CNS agents, Bourguignon and co-workers found that the two orZ/zo-brominated aminopyridazines 4-bromo-6-phenylpyridazin-3-amine and A -benzyl-4-bromo-6-phenylpyridazin-3-amine (82) can be used as substrates in Suzuki arylation reactions without the need of any amino group protection [52]. 

In 2004, Gong and He reported C-5 selective Suzuki arylation of 2-methyl-... 

To deal with the regioselectivity problems observed in Suzuki arylation reactions on 2-substituted 4,5-dichloropyridazin-3(2//)-ones under classical conditions, Matyus, Maes, and Riedl introduced the concept of provisionally masked functionalities (PMF s) [64]. The PMF concept is based on the well-documented regioselective introduction of a methoxy group in the 4 or 5 position of 2-substituted... 

By means of a repetitive Suzuki aryl-aryl cross-coupling method, developed by Schliiter, Wegner and co-workers, the synthesis of solubilized PPP s 6 with a dramatically increased molecular weight (number average up to 100 1,4-pheny-lene units) was possible [12]. 2,5-Dialkyl-substituted PPPs 6 were intensively studied as prototypes of so-called hairy-rod macromolecules, composed of a linear, rigid PPP main-chain and flexible, hairy alkyl side-chains. The individual, shape-persistent macromolecules can be imaged by transition electron microscopy within monolayers [16]. Poly(2,5-di-n-dodecyl-l,4-phenylene) 6 (R -C12H25) revealed a sandwich-type structure with layers of aliphatic side-chains perpendicular and layers of the PPP main-chain parallel to the substrate surface. 

They found that combination of the Ir(T) catalyzed C-H borylation and Suzuki coupling sequence led to a two-step, one-pot C-H Suzuki arylation that enabled direct transformation of the N-Boc pyrrole to the C3 arylated intermediate in 78% yield. Following installation of the required acyl group, an application of their oxidative Pd-catalyzed C-H alkenylation reaction enabled formation of the key structural architecture of the natural deliver the natural product. The orthogonal selectivity characteristics displayed by these C-H functionalization processes makes possible iterative functionalization of the heteroaromatic pyrrole core. Utilization of the highly versatile C-H borylation - Suzuki coupling to install the aromatic functionality opens up possibilities of facile analogue synthesis via this route. 

Ackermann employed a different reaction order to meld 1,2-dihaloaryls together with anilines to access a series of carbazoles, including murrayafoline A (Scheme 2, equations 1 and 2) [23]. Jean and colleagues reported a tandem Suzuki/aryl-Heck protocol to prepare functionalized carbazoles and glycosinine (equation 3) [24]. Larock and Liu synthesized a series of carbazoles and the alkaloid muko-nine via an aryl-Heck reaction, which featured an aryne mediated preparation of the requisite diaryl amines [25]. Willis and coworkers reported an indole synthesis involving Heck arylation followed by double bond isomerization (equation 4) [26]. Urabe and colleagues described a similar aryl-Heck indolization from p-bromo-Al-aryl enamines giving 2-alkylindoles [27]. 

Figure 10.4 (Top) Dependence of the extent of reaction on time for the Suzuki aryl-aryl coupling reaction between 4-fluorohromohenzene and 4-metho3yphenyl-horonic acid catalyzed homogeneously by ( ) Pd(PPh3)4 and heterogeneously by the palladium-containing HATN-network-PIM (A) recycled twice and ( ) recycled three times. (Bottom) Dependence of the extent of reaction on time for the degradation of H2O2 with ( ) low molar mass cobalt phthalocyanine (CoPc) and ( ) the CoPc-network-PIM as a catalyst. Reproduced from Ref. 30 with permission from The Royal Society of Chemistry.

The Masuda borylation/Suzuki arylation (MBSA) sequence starting from N-protected 3-iodoindoles 59 has been extended to the coupling of bromothiazole (13EJOC4564).The optimized conditions involve addition of catalytic amounts of triphenylphosphine to prevent precipitation of palladium in the second step. 

Wallow, T.I. Novak, B.M. (1994) Highly efficient and accelerated Suzuki aryl couplings mediated by phosphine-free palladium sources, J. Org. Chem., 59, 5034-7. 

Bauer, A. Miller, M. W. Vice, S. F. McCombie, S. W. 2001. Suzuki arylation of 1,1-dibromo-l-alkenes Synthesis of tetra-substituted alkenes. Synlett 254—256. 

SCHEME 13.20. A nickel-catalyzed method for the asymmetric Suzuki arylation of racemic a-chloroamides. 

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