Alkene metathesis systems

Two RCM reactions were employed in a new and efficient route to a key chiral intermediate, isoquinuclidine 150, in the synthesis of alkaloid (-F)-catharanthine <06AG(I)5334>. The first RCM makes use of chiral enone 151, derived from L-serine, to generate a chiral dihydropyridinone 152. Intramolecular alkene metathesis of dialkenyl piperidine 153 generates 150, which represents the first example of the use of RCM in the generation of an azabicyclo[2.2.2]alkene system. 

The formation of carbon-carbon bonds has always been one of the key challenges in synthetic organic chemistry, and particularly methods to obtain optically pure products are of fundamental importance. In DCC, however, with the exception of the powerful alkene metathesis reaction, C-C bond formation has only been explored in a few systems [1,5,6,18-20]. 

The trend of structural selectivity can be summarized as degenerate metathesis of terminal alkenes (exchange of methylene groups) > cross-metathesis of terminal and internal alkenes > metathesis of internal alkenes > productive metathesis of terminal alkenes (formation of internal alkene and ethylene).87 Since different catalyst systems exhibit different selectivities, a simple general picture accounting for all stereochemical phenomena of metathesis is not feasible. 

Alkenyl-2-azetidinone systems could be converted to bicyclic (3-lactam carboxylic esters and hence carboxylic acids (Fig. 5) via tandem Ireland-Claisen rearrangement and subsequent alkene metathesis [250],... 

The alkene metathesis reaction arose serendipitously from the exploration of transition-metal-catalysed alkene polymerisation. Due to the complexity of the polymeric products, the metathetic nature of the reaction seems to have been overlooked in early reports. However, in 1964, Banks and Bailey reported on what was described as the olefin disproportionation of acyclic alkenes where exchange was evident due to the monomeric nature of the products [8]. The reaction was actually a combination of isomerisation and metathesis, leading to complex mixtures, but by 1966 Calderon and co-workers had reported on the preparation of a homogeneous W/Al-based catalyst system that effected extraordinarily rapid alkylidene... 

A major drawback of alkene metathesis is lack of control over the stereochemistry of the newly formed double bond. For unstrained systems, E/Z ratios are virtually unpredictable. Alkyne metathesis, on the other hand, can always be combined with subsequent Lindlar hydrogenation, thereby giving access to stereochemically pure 2-olefins. In 1998, Ftirstner and Seidel were the first to report a ring-closing alkyne metathesis [7]. Under high-dilution conditions (0.02 m) and reduced pressure (20 mbar, removal of 2-butyne, solvent 1,2,4-trichlorobenzene (b.p. 214 °C)) the Schrock catalyst was applied to assemble macrocydic... 

Abstract The last half decade has been a period of unprecedented development for the range of transition-metal-catalysed alkylidene exchange reactions collectively known as alkene metathesis. These carbon-carbon bond forming processes have, in a relatively short time, evolved from relative obscurity into a major research area at the forefront of both modern organometallic and synthetic organic chemistry, driven by the rational design of ever more robust and powerful catalytic systems. The advent of modern well-defined catalysts has... 

This work consists of an overview of the major developments in the alkene metathesis reaction since 1997. In view of the breadth of the subject area and the rapid pace of advancement in the field in recent years, this review is not intended to serve as a comprehensive survey, but rather as an account of how the development of novel catalyst systems has made a dramatic impact on the reaction in terms of scope and efficiency/selectivity. 

All the above cascade alkene metathesis reactions are based on the ROM of a cycloalkene moiety. Harrity and co-workers have described the synthesis of functionalized spiro cyclic systems by cascade selective olefin ringclosing metathesis reactions from an acyclic tetraalkene. The selectivity for five-membered ring closure over seven-membered ring closure would be the result of a kinetically favored cyclization process [42] (Scheme 20). The syn-... 

The mechanism described in Scheme 1 (the Chauvin mechanism) is the accepted mechanism of alkene metathesis, and its validity has been demonstrated in two ways. First, classical kinetic studies, including isotopic labeling and crossover experiments performed using poorly defined catalysts, conclusively demonstrated that the carbene mechanism was consistent with the experiments, while the pairwise mechanism was not. More recently, the synthesis of isolable carbene complexes that catalyze the reaction has allowed a more direct observation of the reaction. Each individual step in the Chauvin mechanism has now been observed spectroscopically for several of the well-defined catalyst systems. 

The original catalysts reported for the metathesis of acyclic alkenes were related to alkene polymerization systems. Banks and Bailey reported in 1964 that the heterogeneous cobalt molybdate complexes would promote the metathesis reaction. Since that time a wide variety of catalysts that use Mo, W and Re as Ae active metal in combination with a variety of supports, promoters and activation conditions have been reported. These heterogeneous catalysts are the systems of choice for most industrial fine chemical applications. 

Recently, highly efficient catalysts have been developed that are one component systems and contain a preformed alkylidene or metallacycle as the catalyst initiatorSome of these complexes have shown excellent utility in the synthesis of organic molecules and will be the major topic of Ae last part of this chapter. These complexes will not only change many of the approaches in simple alkene metathesis but will also have a major influence on the future applications in organic and polymer synthesis. 

Related molybdenum catalysts appear to show even more functional group tolerance. To date, the major test of functional group compatibility has been in the synthesis of polymers however, it is anticipated that this activity will persist into acyclic metathesis. Later transition metals are active in the metathesis polymerization of highly functiondized cyclic alkenes. These catalyst systems, which appear to tolerate almost all functional groups, show very low activity for acyclic alkene metathesis. If these systems can be activated, the problems associated with the use of alkene metathesis in the synthesis of multifunctional organics will be solved. 

Considerable progress has been made in the characterization and applications of the ruthenium catalysts that will function in aqueous and protic media. A number of approaches have been made to produce conditions and ligand systems that will allow ruthenium based alkene metathesis in aqueous and protic media to reach the same generality as metathesis in organic solvents. 

Although a number of systems are now available that will allow some metathesis reactions to take place in aqueous solution, the generality and activity of these systems is not yet sufficient to carry out many RCM and cross metathesis reactions with the desired catalyst efficiency. The instability in water of the ruthenium alkylidenes known to date has not allowed alkene metathesis processes in aqueous media to reach the level of utility that is possible in organic solvents. 

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