RCM/elimination

In the field of dihydropyridines, chiral difluoro ester 237a was obtained by RCM (10OL3484) whereas simpler 237b-type esters could even be composed from acyclic starting materials in an efficient one-pot protocol (four-component-reaction / y-alkylation / RCM / elimination sequence) (10JCO713). 

Lovely and coworkers reported an RCM/elimination approach in the synthesis of a benzimidazole (03TL1379). RCM reaction of dienylimidazole 47 with Grubbs second-generation catalyst resulted in formation of the bicyclic structure 48, which upon elimination of water in situ furnished benzimidazole 49 in 45% yield (Scheme 14). 

The Donohoe group used an alternative RCM/elimination strategy for the synthesis of pyridine and pyridazine frameworks (09T8969). Two scenarios for the synthesis of pyridines 55 are outlined in Scheme 17. 

In a similar manner to that for pyridines, pyridazines 68 were synthesized from functionalized hydrazines 66 via pyridazones 67 using an RCM/elimination/ triflation approach (09CC3008). The metathesis precursors 66 were synthesized in two steps from commercially available tosyl hydrazide (not shown). Substituents can be incorporated at aU ring positions, which was clearly exemplified by the introduction of a methyl group in different positions of the pyridazine (Scheme 19). 

Another powerful method for the synthesis of aromatic compounds is elimination of a leaving group after RCM. Schemes 26.13 and 26.14 show two interesting and early examples using an RCM/elimination sequence. Because aromatic compounds prepared in these examples were not the products desired, the yields of these compounds were not shown in the original papers. Evans et al. reported the formation of naphthalene (47) [20]. When RCM of diene 45 having hydroisoquinoline skeleton was carried out, a mixture of 45, RCM product 46, and naphthalene (47) (45 46 47 = 44 25 31) was obtained. The formation of naphthalene (47) was attributed to elimination of the M-tosyl imine by-product Ifom 46. On the other hand, Bassindale... 

Scheme 26.15 shows examples of naphthalene synthesis using an RCM/ elimination sequence reported by Huang and Wang [22], After ring closing of dienes 51, dehydration of the resulting RCM products 52 with silica gel gave naphthalenes... 

In Scheme 26.17, examples of the synthesis of furans and pyrroles using an RCM/elimination sequence reported by Donohoe et al. are shown [24]. Dienes 57 and 60 containing heteroatoms were subjected to RCM, and the resulting RCM products 58 and 61 were treated with trifluoroacetic acid (TFA) to eliminate methanol to afford various furans 59 and pyrroles 62. Donohoe et al. also employed their method successfully to the synthesis of a natural product [24c], As shown in Scheme 26.18, an RCM/elimination sequence of acyclic substrate 63 provided furan 64, and the product 64 was then converted elegantly to a macrocycle, (-)-(Z)-deoxypukalide 65, in a few steps. 

A concise total synthesis of the indole alkaloid dihydrocorynantheol (101) (Scheme 19), that features two RCM steps and a zirconocene-catalyzed carbo-magnesation [68], is a further example of Martin s interest in applying RCM as a key reaction for the construction of alkaloid frameworks [69]. The first RCM step was applied to bis-allyl amide 96. The resulting intermediate 97 was directly subjected to carbomagnesation and subsequent elimination to deliver 98 in 71% yield from 96. Amide 98 was then transformed into acrylamide 99 in... 

In 2003, Efskind and Undheim reported dienyne and triyne domino RCMs of appropriately functionalized substrates with Grubbs type II or I catalysts (Scheme 6.71, reactions a and b, respectively) [151]. While the thermal processes (toluene, 85 °C) required multiple addition of fresh catalyst (3 x 10 mol%) over a period of 9 h to furnish a 92% yield of product, microwave irradiation for 10 min at 160 °C (5 mol% catalyst, toluene) led to full conversion. The authors ascribe the dramatic rate enhancement to rapid and uniform heating of the reaction mixture and increased catalyst lifetime through the elimination of wall effects. In some instances, use of the Grubbs I catalyst was more efficient than use of the more common Grubbs II equivalent. 

Particularly interesting is the reaction of enynes with catalytic amounts of carbene complexes (Figure 3.50). If the chain-length between olefin and alkyne enables the formation of a five-membered or larger ring, then RCM can lead to the formation of vinyl-substituted cycloalkenes [866] or heterocycles. Examples of such reactions are given in Tables 3.18-3.20. It should, though, be taken into account that this reaction can also proceed by non-carbene-mediated pathways. Also Fischer-type carbene complexes and other complexes [867] can catalyze enyne cyclizations [267]. Trost [868] proposed that palladium-catalyzed enyne cyclizations proceed via metallacyclopentenes, which upon reductive elimination yield an intermediate cyclobutene. Also a Lewis acid-catalyzed, intramolecular [2 + 2] cycloaddition of, e.g., acceptor-substituted alkynes to an alkene to yield a cyclobutene can be considered as a possible mechanism of enyne cyclization. 

CM reactions with terpenoids containing two double bonds such as citronellene are hampered by low yields because of RCM competition among other side reactions. Mauduit et al. performed the CM of several terpenoids with n-butyl acrylate and crotonaldehyde using Hoveyda-Grubbs type catalysts containing an aminocarbonyl function [89]. Yields below 43% were obtained in all cases with 1 mol% catalyst. In contrast to these results, the hydrated masked form of citronellene, i.e., dihydromyrcenol, gave 71% yield of the CM product. It was thus proposed that in order to avoid selectivity problems in the CM of terpenoids containing two double bonds, masked derivatives can be used followed by a simple elimination step to recover the olefin functionality. 

An example of realization of a related route toward pyrroles involving assembly of the precursor 173 from the sulfonamide 174, methoxyallene, and iodobenzene, was completed by a RCM reaction, and subsequent acid-induced elimination of methanol, giving the target heterocycle 175 (Scheme 20) <2005EJ01969>. 

The goal of providing a decision area in decision making process is for the convenience of choosing the best maintenance method corresponding to the fault mode. As the majority of less important issues (such as simple function degradation) have been eliminated in the filter area, analysis in the decision area will be more specific and purposeful by contrast with the traditional RCM. Based on the RBI-based analysis of pipelines, different maintenance plans are worked out for pipelines... 

RCM of MBH adducts 144 by Grubbs catalyst (second generation) furnished cyclized products that underwent elimination of water to afford cyano-naphthalenes 145 in excellent yields (Scheme 4.41). 

Subsequently, Donohoe and co-workers also reported the RCM reaction of MBH derivatives 243, and the crude RCM products were further transformed, via elimination of methanol, into the fully aromatized system (a reaction promoted by adding acid). As shown in Scheme 4.78, multi-substituted furans 244 have been prepared in 59-81% yields in a one-pot process. ... 

After masking of the alkyne function by a dicobalthexacarbonyl complex, RCM was used to cyclize the diene 573 (Scheme 9.15). Then, decomplexation enabled a Diels-Alder reaction with the disiloxydiene 575, ensued by elimination of isobutylene. Two hydroxy groups of the resorcylic macrolide (576) obtained were protected and the TBS-ether was cleaved. Thus, dehydration with concluding deprotection of all alcohol functions furnished aigialomycin D (482), in an overall yield of 8%. 

Synthesis of furans and pyrroles based on path A requires a robust synthesis of mixed acetals 22 and 23. As outlined in Scheme 4, 22 and 23 can be readily obtained by the reaction ofaUyHc alcohols and sulfonamides (20 or 21) using paUadium(II) catalysis. After the RCM of 22 and 23, treatment of the intermediates 24 and 25 with add promotes elimination of methanol and results in the formation of furans 12 and pyrroles 13. 

El elimination of ethanol. When a ieri-butyl group was present at the position, methylenation failed (Table 1, entry 7), presumably due to steric reasons. Note that in this system, the RCM transformation using Hov-eyda—Grubbs second-generation catalyst 4 resulted in shorter reaction times and increased yields. 

In the first case (path A), a,p-unsaturated lactams 56 were accessed from substrates of type 57 using RCM. In this route, the amide nitrogen was protected as a benzyloxy group. This benzyloxy protecting group provided an inbuilt access to the pyridine oxidation level via elimination after RCM. The lactam carbonyl moiety could also be transformed into a triflate group (R = OTQ, which is a useful functional handle for further functionalization of the target pyridine 55. In the second case (path B), cylic enones of type 58... 

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