Ring-rearrangement metathesis olefins

We will focus on the development of ruthenium-based metathesis precatalysts with enhanced activity and applications to the metathesis of alkenes with nonstandard electronic properties. In the class of molybdenum complexes [7a,g,h] recent research was mainly directed to the development of homochi-ral precatalysts for enantioselective olefin metathesis. This aspect has recently been covered by Schrock and Hoveyda in a short review and will not be discussed here [8h]. In addition, several important special topics have recently been addressed by excellent reviews, e.g., the synthesis of medium-sized rings by RCM [8a], applications of olefin metathesis to carbohydrate chemistry [8b], cross metathesis [8c,d],enyne metathesis [8e,f], ring-rearrangement metathesis [8g], enantioselective metathesis [8h], and applications of metathesis in polymer chemistry (ADMET,ROMP) [8i,j]. Application of olefin metathesis to the total synthesis of complex natural products is covered in the contribution by Mulzer et al. in this volume. 

Another form of olefin metathesis widely used for piperidine formation is ring-rearrangement metathesis (RRM), as shown below. The versatility of this reaction can be seen in its ability... 

Multiple cyclo olefinic relays are also suitable substrates to promote cascades of RCM-ROM-RCM reactions [9] (Scheme 16). Thus, W-protected polycyclic amines have been synthesized in moderate to good yields, but an increasing number of cyclopentene relays gave rise to less efficient cascade transformations. This ring rearrangement metathesis (RCM-ROM-RCM) has been extensively reported by Blechert and co-workers for its application in the synthesis of natural products [30-34]. 

Fukuyama and coworkers [48] have also utilized an olefin additive in the optimization of a crucial ring-rearrangement metathesis sequence to form the key 5,6-ring system in the synthesis of (-)-isoschizogamine (Scheme 12.27). The tandem metathesis reaction of the norbornene 87 was difficult due to the substitution pattern of norbornene skeleton, which restricted the approach of the Ru catalyst. For example, the treatment of norbornene 87 with the second-generation Hoveyda - Grubbs catalyst 4 at reflux in benzene provided lactone 89 in only 24% isolated yield. To optimize this reaction, the use ofthe modified Hoveyda-Grubbs catalyst 88 [49] and the addition of 20 equiv of 1,6-heptadiene as an additive were quired. The desired lactone 89 was then obtained in 73% yield. 

Apart from cross-metathesis, ROMP, and RCM, there are other less common metathesis reactions. These are acyclic diene metathesis polymerization (ADMET), ring-opening cross-metathesis (ROCM), ring-rearrangement metathesis (RRM), and ethenolysis. A general ADMET reaction is shown by reaction 7.3.1.7. ADMET reactions are generally performed on a,well-defined and strictly linear polymers with unsaturated polyethylene backbones. Ethenolysis is the cross-metathesis of ethylene with an internal olefin. 

Olefin metathesis is a unique carbon skeleton redistribution in which unsaturated carbon-carbon bonds are rearranged in the presence of metal carbene complexes. With the advent of efficient catalysts, this reaction has emerged as a powerful tool for the formation of C-C bonds in chemistry [1]. Olefin metathesis can be utilized in five types of reactions ring-closing metathesis (RCM), ring-opening metathesis (ROM), respective ringopening metathesis polymerization (ROMP), cross-metathesis (CM), and acyclic diene metathesis polymerization (ADMET). 

In some cases the reaction stops at the four-membered ring in others the ring rearranges to give products different from those represented in eqn. (1). In Table 4.1 various types of observed reaction are summarized other than those involved in metathesis of olefins or acetylenes, or of metathesis polymerization. 

It was found that titanacyclobutanes could be prepared by removing the aluminum from 3 with a strong Lewis base in the presence of an olefin, as shown in Eq. 9. These metallacycles were stable with respect to rearrangement to an olefin via a 3 hydride process, and showed a tendency to generate intermediate alkylidene complexes in situ. They ultimately proved to be useful as catalysts for the ring opening metathesis polymerization of a variety of strained olefins. [47,48] It should be noted that the masked titanium methylene complex 3 (Eq. 

A review of olefin metathesis has included the application of Claisen rearrangement and olefin metathesis to prepare intricate targets. " Isomerization issues during the ring-closing metathesis step of a new approach towards pentalenene have been reported (Scheme 74). " ... 

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. ... 

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