Synthesis metathesis/Diels-Alder reaction

The tricyclic compound 20-C, a potential intermediate for alkaloid synthesis, has been prepared by an intramolecular Diels-Alder reaction of the ketone obtained by deprotection and oxidation of 20-B. Compound 20-B was prepared from 20-A using alkyne-ethene metathesis chemistry. Show the mechanistic steps involved in conversion of 20-A to 20-B. 

Another intramolecular ene-yne metathesis followed by an intermolecular metathesis with an alkene to give a butadiene which is intercepted by a Diels-Alder reaction was used for the synthesis of condensed tricyclic compounds, as described by Lee and coworkers [266]. However, as mentioned above, the dienophile had to be added after the domino metathesis reaction was completed otherwise, the main product was the cycloadduct from the primarily formed diene. Keeping this in mind, the three-component one-pot reaction of ene-yne 6/3-94, alkene 6/3-95 and N-phenylmaleimide 6/3-96 in the presence of the Grubbs II catalyst 6/3-15 gave the tricyclic products 6/3-97 in high yield (Scheme 6/3.28). 

Fig. 31 Synthesis of a tricyclic framework using ene-yne metathesis and Diels-Alder reaction. 

The Durham precursor route to polyacetylene is an excellent example of the application of organic synthesis to produce a precursor polymer whose structure is designed for facile conversion to polyacetylene. Durham polyacetylene was first disclosed by Edwards and Feast, working at the University of Durham, in 1980 227). The polymer (Fig. 6 (I)) is effectively the Diels-Alder adduct of an aromatic residue across alternate double bonds of polyacetylene. The Diels-Alder reaction is not feasible, partly for thermodynamic reasons and partly because it would require the polymer to be in the all m-conformation to give the required geometry for the addition to take placed 228). However, the polymer can be synthesised by metathesis polymerization of the appropriate monomer. 

It has been shown that the combination of ring-closing metathesis and Diels-Alder reaction sequences is a useful synthetic tool for the asymmetric synthesis of... 

The total synthesis proceeds in >10 steps on solid phase and includes various transformations, including an asymmetric Diels-Alder reaction, oxidation with singlet oxygen, and olefin metathesis. This synthesis sequence is among the most advanced and demanding solid-phase syntheses developed so far for chemical genomics experiments. It demonstrates that the total synthesis of complex natural products in multi-step sequences on solid phase is feasible. 

Synthesis of carbocyclic systems intramolecular free-radical cyclization, the Diels-Alder reaction, and ring-closing metathesis... 

The concise enantioselective total synthesis of (+)-monomorine I, a 3,5-dialkyl-substituted indolizidine alkaloid, was completed by S. Blechert et al. using a sequential cross-metathesis double reductive cyclization strategy. The enedione substrate was prepared in two steps. The Stetter reaction between the masked equivalent of acrolein and butyl vinyl ketone was followed by a retro Diels-Alder reaction under flash vacuum pyrolysis (FVP) conditions. 

Hardacre and Doherty described the synthesis and use of OSs supported bis(oxazolines) in various copper catalyzed reactions such as Diels-Alder reaction [97] and Mukaiyama-Aldol reactions [98], Starting from mono methyl substituted box ligand, deprotonation followed by alkylation using an excess of dibromopentane provided the required alkyl halide for quatemarisation. After ion metathesis the imidazolium supported box ligand (L12) is isolated in a good 62% overall yield (Fig. 30). 

Cross-enyne metathesis has also been applied to solid-phase synthesis by immobilizing either the alkyne or the alkene (498,499). By combination with a Diels-Alder reaction, this process has been used to create a combinatorial library of various six-membered ring structures (500). Within this theme, intermolecular enyne metathesis is the integral synthetic method used to produce novel amino acid derivatives (501, 502). To this end, the aromatic ring of highly substituted phenylalanines was synthesized through enyne crossmetathesis and cycloaddition. 

The synthesis of 4/5/6, 4/6/6 and 4/7/6 tri- and tetracyclic P-lactams 48 has been carried out via one-pot enyne metathesis and Diels-Alder reactions <04S2665><04EJ04840>. The synthesis of unprecedented inner-outer-ring 2-[tert-butyldimethylsilyloxy] dienes with a carbacepham structure in optically pure form and their totally 7t-facial endo selective Diels-Alder reactions to structurally novel polycyclic P-lactams 49 has been reported <04TL7255>. 

By making use of the viability of inducing intramolecular [4+2] cycloadditions using vinylogous imides as the dienophilic reactant and the application of such a process to the facile synthesis of the tricyclic ABC ring (see Scheme 18), the tetracyclic ABCE unit was constructed (see Scheme 29). The process includes an intramolecular Diels-Alder reaction followed by a novel olefin metathesis reaction to form the azocine ring... 

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