Grubbs first generation

The results obtained with the various metathesis substrates depicted in Scheme 44 demonstrate the lack of a stereopredictive model for the RCM-based formation of macrocycles, not only by the strong influence that may be exhibited by remote substituents, but also by the fact that the use of more reactive second-generation catalysts may be unfavorable for the stereochemical outcome of the reaction. Dienes 212a-f illustrate the influence of the substitution pattern. All reactions were performed with Grubbs first-generation catalyst A... 

Allenes 111 undergo cycloisomerisation in presence of 20 mol% of catalyst 110 (Scheme 5.29) [32]. Interestingly, when the Grubbs first generation catalyst 109 is used in this reaction the ring-closing metathesis is observed [33]. 

Starting from complex IX, Fiirstner developed a homobimetallic phenylindeny-lidene complex XXV (Equation 8.5), and both of these were used in the cyclization of medium-sized rings by RCM. A series of examples is presented which shows that indenylidene complexes are as good as or superior to the classical Grubbs first generation catalyst in terms of yield, reaction rate, and tolerance towards different functional groups (Scheme 8.17) [58]. 

Hebach and Kazmaier reported the synthesis of cyclic peptidomimetics containing an alkylated amino acid via Ugi-4CR of N-terminal-protected aloc-amino acids, allyl isocyanoacetate, and chiral amines in trifluoroethanol. Allylic esters of tripeptides 193 were obtained in high yields and good stereoselectivity. Metathesis with 5% of Grubbs first-generation catalyst gave 16-membered cyclic peptides 194 in 30-50% yield (Scheme 2.69) [101]. 

Banfi and co-workers applied the tandem Ugi reaction/ring-dosing metathesis to the synthesis of unsaturated nine-membered lactams as potential reverse-turn inducers. Reaction of allyl-substituted racemic isocyanoacetates with preformed imines and carboxylic acids gave adducts 195 that were treated with Grubbs first-generation catalyst to give nine-membered lactams 196 (Scheme 2.70) [102],... 

RCM of (. )-], 4-dim cthoxy-2-(prop-l-enyl)-3-(vinyloxy methyl [naphthalene 148 using Grubbs first generation catalyst affords 5,10-dirnethoxy-1 //-bcnzo[g]isochromene in high yield (Equation 70) <2004TL3443>. 

Cyclic diol protecting groups are not always conducive to a successful RCM. For example, when Banwell and McRae submitted acetonide-protected 1,3-diol 28 to the Grubbs first-generation catalyst, none of the desired macrocyle was produced, but cyclohexene 29 was obtained in 81% yield, probably because the acetonide protecting group facilitated interaction of the double bonds of the carboxylic acid portion of the molecule (Scheme 2.11) [24]. To circumvent this problem, substrate 30 was synthesized, where the diol was protected as two silyl ethers, and RCM of this compound led to the desired 18-membered lactone 31 in 70% yield under the same reaction conditions. 

Grubbs first generation metathesis catalyst 145 was found to be an active catalyst for the Kharasch addition, provided its metathesis activity for the chosen olefin is low [206]. Snapper and coworkers found at the same time that the Grubbs I olefin metathesis catalyst is efficient for the Kharasch addition of less activated halides, such as CHC13, 1,1,1-trichloroethane, or ethyl trichloroacetate, to olefins like styrenes, acrylates, or acrolein [207, 208]. 

Olefin metathesis, in particular ring closing metathesis (RCM), remains a popular route to the synthesis of piperidines. This is exemplified in the following references which employed an RCM reaction utilizing Grubbs first generation catalyst (benzyl -... 

Fig. 3. Three well-defined metathesis catalysts Schiock s molybdenum alkylidene (1) and Grubbs first generation (2) and second generation (3) benzylidene cataiysts.

Naturally-occurring fatty acids, such as oleic acid, could serve as feedstocks for metathesis-centered transformations. For example, workers at Dow Chemical Company explored the use of Grubbs first-generation catalyst (23) to promote ethenolysis of methyl oleate (equation 11.18) to form C10 alkenes, which might serve as feedstocks for some of the processes that have already been mentioned in this section.49... 

ADMET polymerization of dienes containing functional groups has been explored to some extent. It appears that diene ethers such as 36 are tolerant of Schrock s W-alkylidene catalysts when undergoing ADMET polymerization, but Grubbs first-generation catalyst is required to successfully polymerize diene alcohol 37,61 because the OH group is too Lewis basic for catalysis by W- and Mo-alkylidenes.62... 

Scheme 5.3-37 Ring-closing metathesis of diallyltosylamide catalyzed by a Grubbs first generation complex in [BMIM][PF6].

The double bonds that are present in some fatty acids may im-dergo olefin metathesis reactions. For example, the ethenolysis of fatty acid methyl esters in the presence of a Grubbs first generation catalyst was used to synthesize cD-unsaturated fatty acid methyl esters (68,69). 

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