Grubbs catalyst benzylidene carbene

Fig. 3.28 ROMP initiators, first, second and third generation Grubbs catalysts (complexes 71, 72, and 73, respectively) 74a-c 3-phenyl-indenylidene replaces the benzylidene carbene...

Olefin metathesis is a useful tool for the formation of unsaturated C-C bonds in organic synthesis, and the reaction has been generally accepted to proceed through a series of metallacyclobutanes and carbene complexe intermediates [40-43]. For this type of reaction, the most widely used catalysts include an alkoxyl imido molybdenum complex (Schrock catalyst) [44] and a benzylidene ruthenium complex (Grubbs catalyst) [43]. The former is air- and moisture-sensitive and has some other drawbacks such as intolerance to many functional groups and impurities the latter has increased tolerance to water and many reactions have been used in aqueous solution without any loss of catalytic efficiency. 

The cyclization of this key intermediate to the fully protected conduritol F derivative 19 showcases the different performance of the standard metathesis catalysts. Despite the excellent track record of the original Grubbs benzylidene carbene complex 2 (7) for the cyclization of 6-membered rings, compound 18 reacts poorly with this particular catalyst in refluxing CH2C12, leading to only 32% conversion after 60h reaction time. This reluctance is likely caused by the preference of diene 18 to adopt a zig-zag-conformation holding the olefin units far apart. 

RCM was the first application of metathesis in synthesis. The reaction is driven to completion not only by loss of ethene from the reaction mixture, but also by entropy as one molecule is converted into two. The mechanism follows that outlined by Chauvin (Scheme 8.61 compare Scheme 8.52). The Grubbs catalyst must first dissociate one of the two phosphine ligands to generate a 14-electron monophosphine carbene. The mechanism then follows the steps laid down by Chauvin through metallacyclobutanes 8.217 and 8.219 and the carbene 8.218. It should be noted that the Grubbs catalyst is the benzylidene complex (R = Ph). This is purely for stability as the methylene complexes are unstable. In the catalytic cycle, R = Ph can only work for the first round, thereafter, it is the methylene species with R = H. 

With the development of an analogous ruthenium benzylidene catalyst 17 by Grubbs and co-workers in 1995, a ruthenium carbene catalyst suitable for the cross-metathesis reaction was in place [34]. Benzylidene 17 exhibited the same impressive tolerance of air and moisture, and the same stability towards functional groups as its predecessor 4, but benefited from easier preparation [35,36] and much improved initiation rates. 

A very efficient group of catalysts are the 2-pyridylethanyl substituted ruthenium carbene complexes 9 and 10. Also this new class of catalyst can be easily prepared, either via the reaction of Grubbs benzylidene catalyst with a 2-(3-butenyl)pyridine or directly via a one-pot procedure for the synthesis of ruthenium carbenes starting from [RuCl2(l,5-cyclooctadiene)] via a ruthenium hydride species, see Scheme 5b. 

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