Transition metal catalysts natural products synthesis

These reactions involve metallate rearrangements , migratory insertion and transition metal-catalysed vinylic substitution reactions. They also perform well in applications in natural product synthesis . Many useful synthetic possibilities arise from application of ring-closing olefin metathesis (RCM) to unsaturated homoaldol products and their derivatives by means of the Grubbs catalyst 3942 4-286 Equation 105 presents some examples. ... 

Ruthenium is not an effective catalyst in many catalytic reactions however, it is becoming one of the most novel and promising metals with respect to organic synthesis. The recent discovery of C-H bond activation reactions [38] and alkene metathesis reactions [54] catalyzed by ruthenium complexes has had a significant impact on organic chemistry as well as other chemically related fields, such as natural product synthesis, polymer science, and material sciences. Similarly, carbonylation reactions catalyzed by ruthenium complexes have also been extensively developed. Compared with other transition-metal-catalyzed carbonylation reactions, ruthenium complexes are known to catalyze a few carbonylation reactions, such as hydroformylation or the reductive carbonylation of nitro compounds. In the last 10 years, a number of new carbonylation reactions have been discovered, as described in this chapter. We ex-... 

Direct carbonylation of organomercurials is a low yielding process that reqnires high temperatures and pressures. However, it can be performed efficiently under milder conditions in the presence of transition metal catalysts, particnlarly, rhodium and palladium. Two important applications of this protocol have recently been reported. The Rh -catalyzed formylation of organomercurials has been applied to the synthesis of a polyol-derived natural product. The organomercury chloride substrate is synthesized by oxymercuration of the corresponding homoallylic alcohol with Hg(OAc)Cl (Scheme 5). 

A wide variety of synthetic processes have been rendered asymmetric through the use of a chiral catalyst. In addition to the types of reaction described above, chiral transition metal catalysts have been used to influence the stereochemical course of isomerization, cyclization, and coupling reactions. As an example, an approach towards the natural product (-)-epibatidine (158) was recently reported by Namyslo and Kaufmann (166). Epibatidine is a potent analgesic and a nicotinic receptor agonist. The synthesis involves an asymmetric Heck-type hydroarylation between the bicyclic alkene (155) and pyridyl iodide (156). A number of bidentate chiral li-... 

Transition-metal catalysts play an ever-increasing and important role in modem chemistry [3]. Numerous transition-metal-catalyzed coupling reactions have been developed and applied in the total synthesis of natural products, such as the Suzuki reaction, the Negishi reaction, the Heck reaction, and many others [4]. Interestingly, the power of transition-metal catalysts is even more visible in the area of domino reactions, where terms such as palladium walking show the value of transition metals in bond formations. 

Phenanthridinone derivatives have been reported to be found in a number of natural alkaloids and exhibit a wide range of biological activities. In the case of starting from bi-functionalized arenes with transition metal catalysts, the intramolecular cyclization of 2-bromo-iV-arylbenzamides via C-H activation is the most direct pathway, which has been applied in the synthesis of anti-hepatitis C virus agents and materials. Remarkably, Yao, Xu and their co-workers developed a one-pot procedure for the synthesis of a pyrrolophenanthridone skeleton via an intramolecular Heck reaction and oxidation of N-(2-bromobenzyl) substituted indoles. Moderate to good yields of the desired products were isolated in one step (Scheme 3.67). From the point view of academic interest, the... 

In the earliest period of complex natural product synthesis, from Robinson s 1917 tropinone synthesis to Eschenmoser and Woodward s 1973 coenzyme synthesis, metal-catalyzed reactions played no great role. In contrast, modern organic syntheses often involve numerous transition metal-catalyzed steps. Main-group compounds, such as BuLi, MeMgBr, or NaBH4, tend to act in stoichiometric quantity as reagents, while the more expensive transition metals, typically complexes of Pd, Rh, or Ru, tend to be used as catalysts and therefore in much lower amounts, for example, 0.1-5 mol% (mmol catalyst per 100 mmol substrate). 

The central six-membered ring unit in the illudalane or pterosin class of sesquiterpenes makes them a suitable target for a proof of the synthetic power of the transition-metal-catalyzed [2 + 2 + 2] alkyne cycloaddition in natural product synthesis. A first example in this field was provided by the intramolecular version of the [2 + 2 + 2] alkyne cyclotrimerization in the synthesis of calomelanolactone (15) [8] and pterosin Z (16), both of which have been isolated Ifom the silver fern Pityrogramma calome-lanos (Scheme 7.4) [9]. Wilkinson s complex served here as the catalyst, and the cyclotrimerization of triyne 13 proceeded at room temperature to give the tricycle 14. The latter was used as a common synthetic intermediate for completion of the synthesis of calomelanolactone (15) and pterosin Z (16) within four and three synthetic steps, respectively. 

In 2008, Piguel and coworkers reported the synthesis of annuloline, the first isolated oxazole-containing natural product (Scheme 16.29a) [61]. 5-Aryloxazole 141 was coupled with bromoalkene 142 in the presence of Cul, diamine 143, and LiOt-Bu to dehver annuloline in 75% yield. Although a number of similar C-H alkenylations of 1,3-azoles with alkenyl halides have been reported using transition metal catalysts [62], Piguel s synthesis is the only report of a natural product (albeit structurally simple) synthesized by intermolecular aromatic C-H alkenylation. 

In addition to transition metals, recent work has demonstrated that strong Lewis acids will catalyze the addition of silanes to alkynes in both an intra- and an intermolecular fashion.14,14a-14c The formation of vinylsilanes from alkynes is possible by other means as well, such as the synthetically important and useful silylcupration15,15a of alkynes followed by cuprate protonation to afford vinylsilanes. These reactions provide products which can be complementary in nature to direct hydrometallation. Alternatively, modern metathesis catalysts have made possible direct vinylsilane synthesis from terminal olefins.16,16a... 

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