Tandem metathesis process

More research efforts have focused on the ring-closing enyne metathesis, which usually [176] provides conjugated vinyl cycloalkenes (cf Fig. 2a, exo mode) useful for further manipulation, but also allows tandem metathesis processes for the formation of polycyclic compounds. 

In a similar way, acetylenes can serve as the relay elements in a tandem metathesis process, and such reactions result in polycyclic dienes. The starting materials are easy to prepare through standard techniques (Eq. 6.26(b)) [46]. 

Additional aspects of enyne metathesis are depicted in Scheme 28. The conjugated diene products of enyne metathesis can undergo Diels-Alder reactions. Enyne metathesis—Diels-Alder can even be performed as a one-pot tandem reaction process, as exemplified by enyne metathesis of 240 in the presence of maleic anhydride. 

A simultaneous intermolecular/intramolecular enyne metathesis process using diynes (e.g., 267) and allylsilane 268 afforded conjugated triene derivatives (e.g., 270). Gyclopropanation was observed as a side-reaction in the tandem enyne metathesis RCM of diene-yne 271. ... 

Starting with -hexane (Cg) metathesis, dehydrogenation should give the corresponding 1-hexene, followed by its homo-metathesis to yield ethylene and decene, which upon hydrogenation, should ideally produce ethane and decane (Cj q products) as the major products (Scheme 2.18, path a). However, this tandem reaction process was not selective since -decane represented <50% of the total primary products of heavy alkanes when the reaction was catalyzed with Ir-2(H2). The authors attributed this unexpected distribution of alkanes to the isomerization of the (x-olefin prior its metathesis, as depicted in pathway b (Scheme 2.18). 

With the observed alkane distribution of both systems (multifunctional catalysts or dual-tandem catalysts), a more selective alkane metathesis reaction would be desirable. Going toward this direction, a homogenous, dual-tandem catalyst system using Ta/Ir has recently been developed, in which the metathesis process has been modified with a dimerization system [146,147]. In this, -heptane was converted into alkene isomers in the presence of tbe in 18% yield. Unfortunately, the final step, the hydrogenation of the resulting alkenes to alkanes, was not accomplished using these reaction conditions. 

R] Although not focused on true tandem/cascade processes, for a review of the synthesis of polycyclics by a combination of enyne metathesis and the Diels-Alder reaction, see Kotha, S. Meshram, M. Tiwari, A. Chem. Soc. Rev. 2009,38,2065-2092. 

One of the most important cascade sequences by rhodium catalysis is the tandem RCM/cross-metathesis (CM) sequence, which includes two metathesis processes. The first process builds up the cyclic framework via an RCM process and then functionalizes the lateral chain of the intermediate vinyl intermediate 5, thanks to a subsequent CCM reaction with a conveniently chosen alkene. 

In addition, these metathesis processes have been utilized in tandem with other reactions to create novel cyclic structures. For example, cross-enyne... 

RCM of a dienyne was also a key step in Mori s recent total synthesis of the alkaloid erythrocarine (447) [183]. The tetracyclic framework of447 was elaborated in the penultimate step, by exposing the hydrochloride of metathesis precursor 445 (1 1 diastereomeric mixture at the carbinol center) to first-generation catalyst A. The tandem process occurred smoothly within 18 h at room temperature leading to tetracycles 446 (1 1 mixture) in quantitative yield. Deprotection of the a-acetoxy isomer 446a led to 447 (Scheme 88). 

A further application of ring-closing metathesis in seven-membered heterocyclic ring formation is in the synthesis of the trans-fused oxpane systems. This process involved tandem RCM/allylstannane-aldehyde cyclizations and interaction of the process provides access to trans-fused polyoxepanes <00S883>. 

Grubbs has reported a similar tandem olefin metathesis-carbonyl olelination process for the preparation of cyclic olefins [31]. In this case, treatment of a keto-olefin with the molybdenum alkylidene 1 at 20°C generates an intermediate alkylidene complex. Under these conditions, competing intermolecular olelination does not occur. However, intramolecular carbonyl olelination of the initially formed alkylidene complex can occur and this results in the formation of a cyclic olefin. This tandem sequence is illustrated by the transformation of keto-olefins... 

N-Dienv11richIoroacetamide 174 (11 = 0, R=H) was, however, subsequently also subject to tandem RCM/ATRC catalyzed by the Grubbs II catalyst 175 (Fig. 43) [254]. The yield of 177 in this reaction was reported to be 82-91%, showing that catalyst 175 is also effective in such tandem processes. Tandem cross-metathesis/ ATRC reactions of N- a 11 v 11 ri c h I o ro acetamides with styrenes catalyzed by 175 produced rather low yields of trichlorinated lactams [254]. Almost at the same time Schmidt and Pohler reported similar tandem RCM/ATRC sequences of 1,6-dienyl trichloroacetates with 5 mol% of 175 and of 1,7-dienyl trichloroacetates... 

A tandem RCM-alkene isomerization sequence to form 5-, 6-, and 7-membered enol ethers was reported by Snapper and co-workers <02JA13390> (Scheme 36). In this process the RCM reaction is run under an atmosphere of 95 5 N2.TI2 to convert the intermediate ruthenium alkylidene into an olefin-isomerization catalyst. Note that alkene migration can convert isomeric metathesis products into the same 2,3-enol ether. A single example of the formation of a 6-membered tosyl enamide was reported in this manuscript. 

Enyne metathesis reactions in the context of natural product synthesis have been reviewed recently by Mori <2007ASC121>. Using the same ruthenium catalyst, a novel tandem diyne cycloisomerization-CM process has been devised to furnish 3,4-divinyl-2,5-dihydrofurans (Equation 57) <1999CC237>. 

Further studies of the regioselective tandem ring opening/cross metathesis of 2-emlo-substituted 7-oxanorbomenes with electron-rich olefins, a process first described in 2004, were reported. Reaction of the 2-exo isomer, like that of the 2-endo isomer, was also found to... 

Theoretical calculations support a low-energy oxidative addition mechanism [26c], Reaction of the unsolvated cationic complex Cp Ir(PMe3)(CH3) with pentane, cyclohexane or benzene in the gas phase also gives Cp Ir(PMe3)(R) as the product. However, a mechanistic investigation of this process by electrospray tandem spectrometry has demonstrated that neither the oxidative addition-elimination mechanism nor the concerted a-bond metathesis mechanism is operative. Instead, the authors proposed a dissociative elimination-addition mechanism which proceeds through a series of 16-electron Ir(III) intermediates [26d]. 

The tendency of the early transition metal complexes to form metallacycles allows combination of the elementary step with other processes such as a-bond metathesis as will be described later. Novel types of catalytic processes are developing in this area, particularly in tandem type organic synthesis enabling construchon of complex molecules with short routes. 

Metathesis of 1,9-decadiene and cyclooctene with trialkoxy- and trisiloxy-substituted vinylsilanes in the presence of Grubbs catalyst, carried out in appropriate conditions, leads to the formation of bis(silyl)diene with a high yield. Similar processes performed with divinyl-substituted siloxane lead to the formation of silicon-containing polymers (via ADMET copolymerization and tandem ROM/CD polymerization), thus opening a new convenient route to synthesis of unsaturated organosilicon copolymers. 

Ru-catalyzed cross-metathesis, hydrogenation, and subsequent ring closure has been successfully combined into a one-pot tandem process for lactone synthesis. Importantly, compatibility between the catalytic systems is crucial to success. By employing the second generation Grubbs-Hoveyda catalyst in addition to Pt02, y- 6-lactones... 

The deactivation of this tandem, dual-catalytic system has been investigated. It was found that the low TONs obtained under these reaction conditions were mainly the result of the decomposition of the olefin metathesis catalyst. It was found that adding an additional amount of olefin metathesis catalyst at the end of a catalytic run reinitiated the process [18]. Therefore, to improve the catalytic efficiency, olefin metathesis catalysts as robust as the Ir-pincer dehydrogenation catalyst and more active at temperatures above 125 °C needed to be developed. A collaboration with Schrock and coworkers allowed for the synthesis of 40 different... 

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