Suzuki cross-coupling reactions compounds

Zhang et al. reported the use of densely functionalized molecules through Suzuki cross-coupling reactions [65]. This synthesis involves the reductive amination of mucaholic acids to form the unexpected lactone (e.g., 82). Compound 82 can then be reacted with phenylboronic acid (83) to form the 2,3-diaryl-a, /J-unsaluralcd-y-lactone 84 as outlined in Scheme 19 in a 78% yield. A similar procedure is outlined in the work of Beilina et al. [66]. 

Chemists working to develop new bioactive compounds try to be alert for new stable heterocycle platforms, but they can easily overlook some of the more, shall we say, exotic ones. When one thinks about the utility of boron in heterocyclic chemistry, the Suzuki cross-coupling reaction typically first comes to mind. In this valuable synthetic reaction <95CRV2457>, a boronic acid group is discarded under basic conditions during a Pd-catalyzed C-C bond formation. There are exceptions, of course, but few chemists appreciate that boron is an element that can be valuable to retain in a molecule so that its unique properties can be utilized. 

Sulfonium salts have been prepared on insoluble supports by S-alkylation of thioethers (Figure 8.2) only as synthetic intermediates. These compounds can be used to alkylate carboxylates [168] and halides [65], or as electrophiles for the Suzuki cross-coupling reaction (see Entry 7, Table 3.48 [169]). Sulfonium salts are also C,H-acidic, and can be used as intermediates for the synthesis of epoxides (Entry 7, Table 15.1 [170]). 

Thus, for our present purposes a similar approach was followed using Suzuki cross-coupling reactions as the key steps in the synthesis of our target compounds. Symmetrically substituted compounds were synthesized in a twofold Suzuki crosscoupling reaction from commercially available p-substituted phenylboronic acids or esters and 4,4 -dibromobiphenyl or 4,4 -biphenyl-bis-boronic acid ester and a p-substituted arylhalide, respectively, using tetrakis (triphenylphosphino) palladium as catalyst together with cesium fluoride as base in dry tetrahydrofurane as shown in Scheme 8.1. The desired products were obtained in respectable yields after heating at reflux for 50 h. 

S. Suzuki, Cross-Coupling Reactions of Organoboron Compounds with Organic Halides, in Metal-catalyzed Cross-coupling Reactions (F. Diederich, P. J. Stang, Eds.), Wiley-VCH, Weinheim, 1998, 49-89. 

The Suzuki cross-coupling reaction is recognized as a novel, abbreviated method for the synthesis of 2-hydroxychrysene, 2-hydroxy-5-methylchrysene, and 8-hydroxy-5-methyl-chrysene from easily accessible reactants (Eq. (8)) [23]. These phenolic compounds constitute precursors for the synthesis of dihydrodiol and bay-region diol epoxide derivatives of chrysene and 5-methylchrysene, which are implicated as the active forms of carcinogenic polynuclear aromatic hydrocarbons. 

Most recently, Monteiro et al. have reported that cyclopalladated compounds derived from the ortho-metalation of benzylic tert-butyl thioethers are excellent catalyst precursors for the Suzuki cross-coupling reaction of aryl bromides and chlorides with phenylboronic acid under mild reaction conditions. A broad range of substrates and functional groups are tolerated in this protocol, and high catalytic activity is attained (Eq. (58)) [93]. 

Deleuze-Masquefa et al. [15] showed that the microwave assisted bimolecular condensation of 2-imidazole carboxylic acid, followed by coupling with ortho-fluoroaniline and subsequent substitution on imidazole ring by Suzuki cross-coupling reaction gave the imidazo[l,2-a]quinoxaline (xiii) analogues in good yields. All the synthesized compounds showed high activities when evaluated for antitumor activities. 

The Suzuki cross-coupling reactions could also be extended to fused pyridazines bearing a halogen atom on the 1,2-diazine nucleus. For example, 7-bromo-3-(2-fluorophenyl)-6-[(1 -methyl-1/7-1,2,4-triazol-5-yl)methoxy] [ 1,2,4]triazolo[4,3-Z ]pyridazine (84) was successfully coupled with phenylboronic acid to yield 3-(2-fluorophenyl)-6-[(l-methyl-l//-l,2,4-triazol-5-yl)methoxy]-7-phenyl[l,2,4]triazolo[4,3-Z ]pyridazine (85) in 51% yield [35]. Compounds like 85 might give access to new anxiolytic drugs since trisubstituted... 

The Suzuki cross-coupling reactions have been explored in the synthesis of drugs and related compounds on the laboratory scale but none have been explored on an industrial scale. A few examples given below are AT II antagonist losartan, a COX-2 selective inhibitor, rofecoxib, a highly potent HMG-CoA reductase inhibitor, NK-104, and anticancer agents epothilones A-B. 

Based on the concept of tandem reaction, a series of synthetic routes have been developed, including an intramolecular Aldol/Oxa-Michael/Aldol/Lactonization synthetic strategy (see Fig. 1.17). The retrosynthetic analysis indicated that the synthesis starts from compound 1.7.21, which first undergoes an intramolecular Aldol reaction then immediately intramolecular Oxa-Michael reaction to form the tricyclic system. Finally through the intermolecular Aldol reaction and intramolecular esterification reaction, the tetracyclic skeleton of Maoecrystal V can be constructed. And 1.7.21 can be provided by the relatively simple materials 1.7.22 and 1.7.23 through Suzuki cross-coupling reaction. 

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