Heteroaromatics natural products synthesis

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. 

Stoichiometric palladium-mediated cyclization was used in natural product synthesis by Boger a number of years ago, as was noted in the introduction. More recently, an intramolecular palladium-catalyzed amination of a heteroaromatic halide has been used as a step in the synthesis of an a-carboline natural product analog [146]. As discussed above, the diphenylhydrazone arylation can also be used for nitrogen heterocycle synthesis [140]. 

Mutants of Pseudomonas putida were found to exhibit an arene dioxygenase activity, which has been exploited in whole-cell reactions for the regio- and enantioselective preparation of cw-dihydrodiols starting from benzene, substituted benzenes, and polycyclic or heteroaromatic compounds [48], The products are invaluable precursors for natural product synthesis, as exemplified in Scheme 8 [49],... 

D. SYNTHESIS OF HETEROAROMATIC NATURAL PRODUCTS VIA Pd-CATALYZED CROSS-COUPLING... 

Natural product synthesis as a test of newly developed methodologies, for example, partial reduction of furans and pyrroles, nucleophilic addition to pyridinium salts. Os-catalyzed oxidative cyclization for the synthesis of tet-rahydrofurans and pyrrolidines, tethered aminohydroxylation of aUcenes, and ring-closing- and cross-metathesis for the constmction of heteroaromatics 12CC11924. 

The Friedel-Crafts reaction is one of the most important and versatile tools for the formation of carbon-carbon bonds in the synthesis of substituted aromatic and heteroaromatic compounds present in numerous natural products and drugs. Catalytic asymmetric variants using either metal complexes or organic molecules attracted considerable attention over the last few years. 

Thus, radical addition reactions provide a useful means of functionalising pyridines, quinolines and isoquinolines, particularly when it is reasonable to employ the heteroaromatic base in excess. Intramolecular variants of the reaction are devoid of that limitation and have been widely exploited in the synthesis of nitrogen-containing heteroaromatics. The mildness of the reaction conditions have found favour in natural products total synthesis and medicinal chemistry programs. These bare testament to the reactions worth and have raised its stature from academic curiosity to useful synthetic tool. 

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. 

The constraction of heteroaromatic compounds via Pd-catalyzed cross-coupling reactions is discussed in detail in Sect. III.2.7. Among all of the available methods, the use of Pd-Zn and Pd-B cross-coupling in the synthesis of natural products is particularly noteworthy. Some of the representative examples of natural product syntheses are shown in Table 4. 

Heteroaromatic motifs are not the only accessible products of a cycloaddition/cycloreversion strategy. Cleverly shaped six-membered dienes with an intrinsic leaving group might also act as precursors for phenyl moieties. A definitely irreversible cycloreversion tailors this route for the integration of arenes into strained scaffolds. Beaudry and co workers [12] embarked on the synthesis of the conforma-tionally chiral macrocyclic natural product cavicularin. A vinyl sulfone moiety, acting as an alkyne equivalent, underwent a Diels-Alder reaction with a neighboring... 

Current interest in the synthesis of natural products containing heteroaromatic moieties as building blocks for pharmaceutical industries, material science, and supramolecular chemistry has resulted in considerable effort in developing new synthetic methods [101]. 

The synthesis of aromatics and heteroaromatics is an important endeavor which, as for any class of organic materials, thrives on innovative strategies and economical methods to solve demanding problems in the construction of polysubstituted systems and complex molecules including natural products. From an indust perspective, tbe task is amply recognized from the ct that > 80% of today s commercial pharmaceuticals and agrochemicals embody aromatic or heteroaromatic components [7]. Aside from electrophilic substimtion, numerous methods, based on aromatics as well as non-... 

The area of C—activation has experienced a flurry of activity over the past two decades and transformations such as those summarized and described herein are fast gaining in their popularity as powerful tools with which the organic chemist can design and construct heteroaromatic molecules. In addition, these metal-catalyzed C—H bond functionalization reactions have had a significant impact on the synthesis of natural products, pharmaceuticals, and functional organic materials. 

Asymmetric hydrogenation of heteroaromatic compounds provides a straightforward synthetic pathway to access enantioenriched heterocycles, which are of great importance in the synthesis of pharmaceuticals and natural products. Rueping et al. reported several examples of enantioselective cascade transfer hydrogenation reaction of heteroaromatic substrates under metal-free conditions [19,20]. The same group also developed a cascade reaction between enamines 42 and oc,P-unsaturated... 

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