Domino metathesis

Substrate-Based Approach the Metathesis/Metathesis Domino Process... 

Scheme 11.9 Metathesis domino reaction toward erythravine and erythrocarine.

RRM is not limited to cyclopentene derivatives, although applications of such metathesis domino process in six-membered cyclo-oleflns have seldom been reported. Even though ring rearrangement of cyclohexenes to five-membered heterocycles is thermodynamically disfavored, synthesis of tetrahydropyridine... 

The cross metathesis of acrylic amides [71] and the self metathesis of two-electron-deficient alkenes [72] is possible using the precatalyst 56d. The performance of the three second-generation catalysts 56c,d (Table 3) and 71a (Scheme 16) in a domino RCM/CM of enynes and acrylates was recently compared by Grimaud et al. [73]. Enyne metathesis of 81 in the presence of methyl acrylate gives the desired product 82 only with phosphine-free 71a as a pre-... 

Within this chapter, two sections are devoted to rhodium and ruthenium. The two main procedures using rhodium are first, the formation of 1,3-dipoles from diazocompounds followed by a 1,3-dipolar cycloaddition [10] and second, hy-droformylation [11], The ruthenium-catalyzed domino reactions are mostly based on metathesis [12], with the overwhelming use of Grubbs I and Grubbs 11 catalysts. 

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]. 

The most important ruthenium-catalyzed domino process is based on a metathesis reaction. Nonetheless, a few other ruthenium-catalyzed processes have been employed for the synthesis of substituted 3,y-unsaturated ketones, as well as unsaturated y-lactams and allylic amines. 

The main reason for the rapid development of metathesis reactions on a laboratory scale (the reaction itself had been known for quite a long time) has been the development of active and robust second-generation ruthenium catalysts (6/3-14 to 6/3-16), which usually provide better yields than the first-generation Grubbs catalysts (6/3-9 or 6/3-13) (Scheme 6/3.2). This also reflects the huge number of domino processes based on ruthenium-catalyzed metathesis, which is usually followed by a second or even a third metathesis reaction. However, examples also exist where, after a metathesis, a second transition metal-catalyzed transformation or a pericyclic reaction takes place. 

A domino metathesis process using the enyne 6/3-54 and ethylene as substrates was developed by Arjona, Plumet and coworkers (Scheme 6/3.15) [244]. Interestingly, by using catalyst 6/3-15 (Gmbbs II), the pyrrolidone 6/3-55 was obtained in 98% yield as the only product, whereas with catalyst 6/3-13 (Grubbs I), compounds 6/3-56 (60%) and 6/3-57 (25%) were formed. 

In addition to terpenes (as described above), carbohydrates have also been used as substrates in domino metathesis reactions, the aim being to synthesize enan-tiopure polyhydroxylated carbocyclic rings. These structures are components of several biologically active compounds such as aminoglycoside antibiotics [254], inositol phosphates [255], and carbanucleosides [256]. An efficient entry to this skeleton was developed by Madsen s group using a domino RCM/CM of the carbohy-... 

Scheme 6/3.24. Domino metathesis/Heck reaction under different conditions.

Scheme 6/3.25. Domino metathesis/Pauson-Khand reaction.

A combination of a metathesis and a Diels-Alder reaction was published by North and coworkers [263]. However, this is not a true domino reaction, as the dienophile (e. g., maleic anhydride) was added after the in situ formation of the his-butadiene 6/3-89 from the fois-alkyne 6/3-88 and ethylene. The final product is the fois-cycloadduct 6/3-90, which was obtained in 34% yield. Using styrene as an un-symmetrical alkene instead of ethylene, the mono-cycloadduct 6/3-91 was formed as a mixture of double-bond isomers, in 38% yield (Scheme 6/3.26). 

Scheme 6/3.27. Domino metathesis/Diels-Alder reaction.

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). 

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... 

Scheme 6/4.29. Enantioselective domino ring-opening/ring-closing metathesis with a Mo-catalyst.

Scheme 10.20. Microwave-assisted domino metathesis reaction.

Scheme 6.71 Dienyne (reaction a) and triyne (reaction b) domino ring-closing metathesis reactions.

Double addition of Grignard reagents to A-glycosyl nitrones (336), in a domino fashion, affords hydroxylamines. Their usefulness has been shown with the synthesis of pyrroloazepine (418) via a ring closing metathesis key step (Scheme 2.187) (564). 

RCM, followed by dihydroxylation of the double bond, is one of the most used methods for the synthesis of these compounds. For two syntheses of (—)-swainsonine 230, the five-membered ring is formed by RCM, followed by cis-dihydroxylation. Blechert et al. <2002JOC4325> prepared the precursor 2,5-dihydropyrroline 234 by domino ring-opening/ring-closing metathesis of an amino cyclopentene derivative 233 (Scheme 49). 

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