Metathesis tandem reaction

Figure 3.42 shows some examples of such tandem-metathesis-olefination reactions. 

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... 

As vinyl ethers were known to be poor substrates in Ru-catalyzed olefin metath-eses, it has been difficult to obtain cydic enol ethers by RCM of the vinyl ethers. Recently, a novel method to obtain cyclic enol ethers has been reported, which afforded cydic enol ethers directly from easily prepared dienes containing an allyl ether moiety [46]. Treatment of 70 with diene 99 in CH2CI2 in the presence of small amount of H2 resulted in a formation of dihydropyran 101 (Eq. 12.40). Treatment of 70 with H2 has been thought to produce an active catalyst for the olefin isomerization, and only metathesis products are formed until a small amount of H2 is introduced in the reaction. These results implied that this reaction most likely proceeded by way of a formation of the cyclic olefin 100, which was subsequently converted to dihydropyran 101 by the newly formed isomerization catalyst. In addition to the tandem reaction shown in Eq. 12.40, another method for obtaining cydic enol ethers from allyl ethers has also been demonstrated [46b]. This method induded addition of the hydride donor, such as NaBH4, to the reaction solution after the metathesis reaction had been completed. Although attempts to observe an active species for olefin isomerization in the presence H2 failed, these results suggested participation of hydride species in the olefin isomerization. 

Recently, Floveyda and Schrock have developed molybdenum-based catalysts (i.e. 744a,b) for an asymmetric ring-opening metathesis (AROM) reaction (Scheme 121) (98JA4041, 98JA9720, 99JA11603). Using a tandem AROM/RCM sequence, they examined the asymmetric synthesis of several heterocyclic compounds. For example,... 

Tandem reactions. The multiple activities of the Ru catalysts enable development of valuable tandem reactions. Further extension of the carbon chain of a conjugated enal obtained from a cross-metathesis reaction is readily achieved on treatment with diazoacetic esters to give alkadienoic esters. ... 

More complex small molecules can also be made by metathesis cascades and tandem reaction sequences involving olehn metathesis components [41], The examples illustrated in Fig. 4.13 include inter- and intramolecular enyne metathesis between an olefin and an alkyne [42], ring-opening cross metathesis to form new substituted acyclic olefins [43], ring-opening ring-closing sequences... 

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. 

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). 

Scheme 2.18 The desired products for n-hexane metathesis via tandem reactions.

Recently, our group has reported the feasibility of the Sn2 reaction for the stereoselective synthesis of substituted O-heterocycles (Scheme 3.2) [15]. We applied the intramolecular 8 2 reaction in conjunction with an olefin cross-metathesis (CM) reaction (tandem CM/Sn2 reaction) to the stereoselective synthesis of the 2,3-frani-2,5-fra j-tetrahydrofuran of subglutinol B (3.15). 

In comparison with the previous examples, Metz and coworkers developed a similar strategy applying selective tandem ene-yne-ene RCM to assemble a 5/7 bicyclic framework [75]. In their total synthesis of sesquiterpene natural products (—)-clavukerin A (94) and (—)-isoclavukerin A (95) (Fig. 27), treatment of dienyne precursors (96) and (97) with phosphane-free Hoveyda-Blechert catalyst under an ethylene atmosphere cleanly afforded ( )-clavukerin A (94) and ( )-isoclavukerin A (95) in 53% and 55% yields, respectively. The high selectivity could also be explained by the preferential initiation of metathesis on the less substituted olefin in this tandem sequence. Similarly, Metz and coworkers utilized this tandem reaction in a more complex system to construct efficiently a 5/61116 tetracyclic skeleton and... 

Ring-closing olefin metathesis with Grubb s catalyst after a zinc-mediated tandem reaction on a methyl 6-iodo-glycoside is an elegant method to lead to a protected hydroxylated aminocycloheptene (Figure 8). 

In 2001, the Grubbs group reported the use oftheirseeondgeneration ruthenium complex [(SIMes)RuCl2(=CHPh)(PCyj)] 57 in tandem metathesis/TH reactions leading to the formation of a series of unsaturated heteroeyclic alcohols in <56% overall yield. This strategy was notably used for the preparation of (R)-(-)-muscone, a natural product with a pleasant fragranee. 

Stmcture 3.26 is that of a water-soluble metathesis (see Section 7.3) catalyst. It illustrates the application of ESI-tandem mass spectrometry for mechanistic studies on metathesis. On reaction with H2C=CHAr (Ar Ph), 3.26 eliminates styrene and forms another carbene complex 3.27. This is shown by reaction 3.2.5.1. 

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