Biaryl coupling natural products

Qudguiner s group enlisted a combination of directed metalation and a Pd-catalyzed cross-coupling reaction for the construction of heteroaryl natural products [49]. One example was the total synthesis of bauerine B (64), a fl-carboline natural product [50]. Ort/zo-lithiation of 2,3-dichloro-iV-pivaloylaminobenzene (61) was followed by reaction with trimethylborate to provide boronic acid 62 after hydrolysis. The Suzuki reaction between 62 and 3-fluoro-4-iodopyridine led to the desired biaryl product 63 contaminated with the primary amine (ca. 30%), both of which were utilized in the total synthesis of bauerine B (64). Another fl-carboline natural product, the antibiotic eudistomin T (65), and a few other hydroxy 3-carbolines have also been synthesized in the same fashion [3, 51]. 

Similar types of nucleophilic substitutions have also been carried out when PIFA is activated by two equivalents of Lewis acids such as trimethylsilyl triflu-oromethanesulfonate (TMSOTf) and BF3 Et20 or heteropolyacid in standard solvents such as CH2C12 and MeCN. These reactions were applied to intramolecular reactions by the same authors leading to biaryls (49) [54-57], quinone imine derivatives (50) [58], and dihydrobenzothiophens (51) [59], which are important structures of bioactive natural products [Eqs. (7)-(9)]. Dominguez and co-workers have expanded the above biaryl coupling reaction to the syntheses of benzo[c]phenanthridine system (52) [60] and heterobiaryl compounds (53) [61] [Eqs. (10,11)]. 

Transition metal-catalyzed cross-coupling is now recognized to be one of the most powerful carbon-carbon bond-formation reactions [1], The palladium-catalyzed coupling of aryl halides or their synthetic equivalents, for example aryl triflates, with arylmetals is very often employed in the synthesis of biaryl molecules, whose skeletons are found in a wide range of important compounds including natural products and organic functional materials [1-3]. 

Further extensive comparisons of various available options are beyond the scope of this chapter. Readers are referred to a review by Snieckus [59] and other appropriate references [60]. A large number of biaryls, including drugs, natural products and other optically active derivatives, as well as oligomers and polymers of interest in material sciences have been synthesized using Pd- or Ni-catalyzed aryl-aryl coupling, as indicated by the representative examples shown in Schemes 1-17, 1-18, and 1-19). 

The Suzuki coupling reaction is a powerful tool for the construction of biaryl compounds and their homologues, which are key structural elements of various natural products, polymers, and compounds of medicinal interest. Aryl boronic acids and their esters are the usual substrates in reactions with aryl or heteroaromatic halides and... 

The total synthesis of the proteasome inhibitor cyclic peptide TMC-95A was accomplished by. S.J. Danishefsky and co-workers. The biaryl linkage in the natural product was constructed by a Suzuki cross-coupling between an aryl iodide and an arylboronic ester derived from L-tyrosine. The required arylboronic pinacolate substrate was prepared using the Miyaura boration. The aryl iodide was exposed to b/s(pinacolato)diboron in the presence of a palladium catalyst and potassium acetate in DMSO. The coupling proceeded in high yield and no symmetrical biaryl by-product was observed. 

The first total synthesis of the potent antibiotic marine natural product ( )-spiroxin C was completed by T. Imanishi et al., who employed a TBAF-activated Suzuki cross-coupling as the key step to form the biaryl linkage. The coupling partner naphthylborate ester was prepared using the Miyaura boration. 

Anctil, E. J. G., Snieckus, V. The directed ortho metalation-cross coupling symbiosis. Regioselective methodologies for biaryls and heterobiaryls. Deployment in aromatic and heteroaromatic natural product synthesis. J. Organomet. Chem. 2002, 653,150-160. 

The intermolecular examples of synthetic value are self-couplings, e.g. formation of the dimer (43) from benzylsesamol, in 85% yield using vanadium oxytrifluoride preparation of the biaryl (44 95%), from 4-methylveratrole, employing iron(III) chloride supported on silica and synthesis of 4,4 -dimeth-oxybiphenyl (69%) fr om anisole by oxidation with thallium(III) trifluoroacetate in the presence of catalytic palladium(II) acetate. This approach has been used in a natural product synthesis. The dimers (45) and (46) were prepared from appropriate derivatives of gallic acid, and transformed into schizandrin C (47) and an isomer respectively. ... 

Biaryl C-C bond formation, via metal-catalyzed cross-coupling tactics, is a widely used transformation in the synthesis of both complex natural products and medicinal agents. Efficient catalytic methods have emerged for the union of complex... 

The very large variety of aryl-aryl coupling reactions developed in the last decades exceeds the scope of this article. An excellent review on the formation of biaryls with special attention to the synthesis of biaryl natural products was published by Bringmann et al. [93 a] in 1990, further reviews on the Stille [94,95a], Suzuki [95], and Heck [78,79] coupling reactions appeared more recently. This survey will present some selected examples of aryl-aryl coupling and condensation reactions described in recent years with special attention on... 

As mentioned in Section 3, oxidative phenolic coupling plays an important role in the biosynthesis of a wide range of natural products. This stimulated the application of this reaction to the biomimetic synthesis of natural biaryls. Unlike the in vivo processes, very probably following a radical dimerization pathway [91] yields of in vitro syntheses are generally moderate or low. Classical work in this field has been extensively reviewed [92], and important developments after the 70s will therefore be summarised here. 

Biaryl structures are found in a wide range of important compounds, including natural products and organic functional materials [8,80,81]. One of the most common and useful methods for preparing biaryls is the palladium-catalyzed coupling of aryl halides with arylmetals (Scheme 1, mechanism A). On the other hand, aryl halides have been known to couple directly with aromatic compounds as formal nucleophiles under palladium catalysis. While the intramolecular cases are particularly effective, certain functionalized aromatic compounds such as phenols and aromatic carbonyl compounds, as well as... 

Regioselective ortho metalation-cross coupling for biaryls and heterobiaryls in aromatic and heteroaromatic natural product s)mthesis 02JOM(653)150. 

Synthesis of biaryls via Pd- or Ni-catalyzed aryl-aryl coupling has found many attractive apphcations in the synthesis of ofigo- and polyaryls and natural products containing biaryls. The former topic is discussed in Sect. IH.2.17.2, and the latter is further supplemented in Table 1 of Sect. IH.2.18. 

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