Ring-closing metathesi

Synthesis of azasugars and alkaloids via ring-closing metathesis 99EJ0959. 

When a mixture of alkenes 1 and 2 or an unsymmetrically substituted alkene 3 is treated with an appropriate transition-metal catalyst, a mixture of products (including fi/Z-isomers) from apparent interchange of alkylidene moieties is obtained by a process called alkene metathesis. With the development of new catalysts in recent years, alkene metathesis has become a useful synthetic method. Special synthetic applications are, for example, ring-closing metathesis (RCM) and ring-opening metathesis polymerization (ROM) (see below). 

The reversal of ring-closing metathesis, namely ring-opening metathesis, is also a synthetically useful reaction. With strained (small-ring) cycloalkenes, e.g. 12, the equilibrium of the reaction lies on the side of the open-chain product 13 ... 

In a reiterative approach, enol ether epoxidation with DM DO has been coupled with C-C bond fonnation and ring-closing metathesis to provide trans-fused THP ring systems [82],... 

Kishi s synthesis 290 ring closing metathesis 302 ring expansion 65, 98... 

Scheme 1 Chauvin mechanism for ring-closing metathesis [4]...

As stated above, olefin metathesis is in principle reversible, because all steps of the catalytic cycle are reversible. In preparatively useful transformations, the equilibrium is shifted to one side. This is most commonly achieved by removal of a volatile alkene, mostly ethene, from the reaction mixture. An obvious and well-established way to classify olefin metathesis reactions is depicted in Scheme 2. Depending on the structure of the olefin, metathesis may occur either inter- or intramolecularly. Intermolecular metathesis of two alkenes is called cross metathesis (CM) (if the two alkenes are identical, as in the case of the Phillips triolefin process, the term self metathesis is sometimes used). The intermolecular metathesis of an a,co-diene leads to polymeric structures and ethene this mode of metathesis is called acyclic diene metathesis (ADMET). Intramolecular metathesis of these substrates gives cycloalkenes and ethene (ring-closing metathesis, RCM) the reverse reaction is the cleavage of a cyclo-... 

Interconversion of - and Z-macrocycles in metathesis reactions proceeds via a ring-opening metathesis/ring-closing metathesis sequence thus, more... 

Alkyne cross metathesis Acyclic diene metathesis Asymmetric ring-closing metathesis Asymmetric ring-opening metathesis Cross metathesis... 

RCM. See Ring-closing metathesis (RCM) Reaction by-products, removing, 83 Reaction extrusion, 204 Reaction index, 237 Reaction injection molding (RIM), 205 Reaction-in-mold (RIM) nylon, 149 Reaction kinetics, 76, 77 Reaction mechanisms, polyesterification, 66-69... 

Ring-closing metathesis (RCM), 432, 434 Ring-opening metathesis polymerization (ROMP), 432, 435, 436 Ring-opening polymerization, 18,... 

The diene core does not necessarily need to remain intact, but can rather be cleaved to enable further functionalization. Taking advantage of the diastereomeric s vitch , such a strategy was implemented together with a ring closing metathesis step in the total synthesis of undecenolides like cladospolide [258,259]. 

With a-monosubstituted ylides the oxidation results in the formation of alkenes (by subsequent Wittig reaction on the intermediate aldehyde). A recent example of such synthesis is found in the preparation of all-(Z)-cyclododecate-traene by oxidation of the appropriate bis-ylide [33]. It must be pointed out that an approach of the same macrocycle based on ring closing metathesis was found ineffective. 

A nice application of this reaction for the synthesis of cyclic a-sulfanylphos-phonates 63 has been reported [42]. It involves a Rh(II)-catalyzed [2,3]-sigmatropic rearrangement and a ring-closing metathesis of the resulting a-(S-allyl) y,d-unsaturated phosphonates 62 (Scheme 16). However, the last step occurs with a low yield (19%) when R = H. 

The last decade has witnessed the growing use of olehn metathesis in organic synthesis.Ring closing metathesis RCM, Eq. (6)] and ring opening metathesis [ROM, Eq. (7)1 as well as a combination of these transformations have resulted in providing opportunities to build molecules of interest and importance. 

The role of complexes 23-28 as catalyst precursors in the ring closing metathesis reactions was investigated. Three different diene substrates diethyldiallyl-malonate (29), diallyltosylamine (30). and dielhyldi(2-methylallyl)malonate (31) were added to the NMR tubes containing a solution of 5 mol% of catalyst precursor in an appropriate deuterated solvent. The NMR tubes were then kept at the temperatures reported in Table X. Product formation and diene disappearance were monitored by integrating the allylic methylene peaks in the H NMR spectra and the results are presented in Table X and the catalytic transformations are depicted in Scheme 3. 

A systematic investigation of the ring-closing metathesis of 138 in the synthesis of a range of fourteen-membered ring lactams 139 and lactones has been reported by Weiler. The geometry of the resulting double bond was determined, the position of the olefin was broadly varied. The ratios obtained were compared to that derived from molecular mechanics calculations, Eq. (15), Table 4 [34]. 

Until now, the most efficient approach to synthesize Freidinger lactams 147 started from a resin-bound cinnamylamine 144. A Fukuyama-Mitsunobu reaction to 145 followed by sulfonamide cleavage and a consecutive appropriate acylation built up the diene 146, which underwent ring-closing metathesis involving Grubb s catalyst 123 to generate the desired lactams 147 (Scheme 27, Table 5) [35d]. 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Pa]ladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 Nicolaou KC, King NP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natmal Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

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