Metathesis Reactions in Domino Processes

Domino Processes Featuring Solely Metathesis Events 

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Scheme 2.1 depicts the structure of some of the catalysts that have been used most often for metathesis reactions in domino processes. 

As illustrated by the schemes above, metathesis reactions in domino processes have swiftly become an established tool in modern organic synthesis. Especially, RRM and domino dienyne metathesis have found extensive uses and will surely continue to catch the attention of synthetic chemists as elegant and atom-economic transformations that allow a quick enhancement of molecular complexity. Next to combinations of metathesis events only, the incorporation of non-metathesis steps into true domino processes has advanced to a remarkable level and will certainly provide even more opportunities in the years to come. 

As discussed earlier in detail, metathesis reactions have been used in extensio in domino processes. Almost all published examples employ Grubbs I and II catalysts... 

Enyne metathesis/metallotropic [l,3]-shift domino processes are also valuable for natural product synthesis [33c,d]. Reaction of substrate 168 with cis-l,4-diacetoxy-2-butene in the presence of Grubbs catalyst 2 generated the intermediate ruthenium alkinyl carbene through a relay RCM with the hberation of 2,5-dihydrofuran followed by metallotropic [l,3]-shift and terminating (Z)-selective CM with the co-olefin to yield the conjugated enediyne 169 (Scheme 2.58) [33c]. The antitumor active Panax ginseng constituent (3R,9R,10R)-panaxytriol was readily synthesized from 169 in six steps. 

Metathesis events and substitution reactions can be readily combined in attractive domino processes. Thus, a dual catalysis with palladium and ruthenium complexes... 

There are many combinations possible of metathesis reactions that can be used in domino metatheses, increasing process complexity with the number of transformations included. Natural product syntheses with ring-closing metathesis (RCM)-cross-metathesis (CM) sequences are described in this section. Ene-ene and ene-yne-ene cascade reactions in a two-metathesis step process will also be discussed. 

The domino processes discussed so far concern intramolecular reactions. Extension of the intramolecular domino metathesis processes described in previous sections to an intermolecular reaction, namely, CM, was also successfully applied in organic synthesis (Scheme 11.22). Although CM is afflicted with difficulties in E/Z selectivity and chemoselectivity (three different products are possible in a reaction with two different olefins), the choice of suitable substrates and catalysts alleviates the limitation of these problems. Both mono- and bicycles are suitable substrates. In this case, however, the loss of ring strain, which usually shifts the domino metathesis process toward the desired product in RRM of bicycUc structures, does not guarantee a successful reaction, as CM displays the main origin of side reactions. 

Grigg and coworkers developed bimetallic domino reactions such as the electro-chemically driven Pd/Cr Nozaki-Hiyama-Kishi reaction [69], the Pd/In Barbier-type allylation [70], Heck/Tsuji-Trost reaction/1,3 dipolar cycloaddition [71], the Heck reaction/metathesis [72], and several other processes [73-75]. A first example for an anion capture approach, which was performed on solid phase, is the reaction of 6/1-134 and 6/1-135 in the presence of CO and piperidine to give 6/1-136. Liberation from solid phase was achieved with HF, leading to 6/1-137 (Scheme 6/1.30) [76]. 

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