Synthesis precatalysts

Amino and Iminophosphine Chloro Ruthenium Precatalysts Synthesis. 54... 

Abstract For many years after its discovery, olefin metathesis was hardly used as a synthetic tool. This situation changed when well-defined and stable carbene complexes of molybdenum and ruthenium were discovered as efficient precatalysts in the early 1990s. In particular, the high activity and selectivity in ring-closure reactions stimulated further research in this area and led to numerous applications in organic synthesis. Today, olefin metathesis is one of the... 

Although olefin metathesis had soon after its discovery attracted considerable interest in industrial chemistry, polymer chemistry and, due to the fact that transition metal carbene species are involved, organometallic chemistry, the reaction was hardly used in organic synthesis for many years. This situation changed when the first structurally defined and stable carbene complexes with high activity in olefin metathesis reactions were described in the late 1980s and early 1990s. A selection of precatalysts discovered in this period and representative applications are summarized in Table 1. 

We will focus on the development of ruthenium-based metathesis precatalysts with enhanced activity and applications to the metathesis of alkenes with nonstandard electronic properties. In the class of molybdenum complexes [7a,g,h] recent research was mainly directed to the development of homochi-ral precatalysts for enantioselective olefin metathesis. This aspect has recently been covered by Schrock and Hoveyda in a short review and will not be discussed here [8h]. In addition, several important special topics have recently been addressed by excellent reviews, e.g., the synthesis of medium-sized rings by RCM [8a], applications of olefin metathesis to carbohydrate chemistry [8b], cross metathesis [8c,d],enyne metathesis [8e,f], ring-rearrangement metathesis [8g], enantioselective metathesis [8h], and applications of metathesis in polymer chemistry (ADMET,ROMP) [8i,j]. Application of olefin metathesis to the total synthesis of complex natural products is covered in the contribution by Mulzer et al. in this volume. 

Complex 25 was also used in an efficient one-pot synthesis of ruthenium-based precatalysts developed by Werner et al. [17a,b] it is generated in situ from RuCl3, H2, PCy3, magnesium, and 1,2-dichlorethane. Upon reaction of 25 with... 

Fig. 27 Synthesis of pentaphenyl ferrocene oxazoline palladacycle precatalyst 53-Cl...

The theoretical approach involved the derivation of a kinetic model based upon the chiral reaction mechanism proposed by Halpem (3), Brown (4) and Landis (3, 5). Major and minor manifolds were included in this reaction model. The minor manifold produces the desired enantiomer while the major manifold produces the undesired enantiomer. Since the EP in our synthesis was over 99%, the major manifold was neglected to reduce the complexity of the kinetic model. In addition, we made three modifications to the original Halpem-Brown-Landis mechanism. First, precatalyst is used instead of active catalyst in om synthesis. The conversion of precatalyst to the active catalyst is assumed to be irreversible, and a complete conversion of precatalyst to active catalyst is assumed in the kinetic model. Second, the coordination step is considered to be irreversible because the ratio of the forward to the reverse reaction rate constant is high (3). Third, the product release step is assumed to be significantly faster than the solvent insertion step hence, the product release step is not considered in our model. With these modifications the product formation rate was predicted by using the Bodenstein approximation. Three possible cases for reaction rate control were derived and experimental data were used for verification of the model. 

Often a suitable potentiometric indication for Lewis titrations is not available, whereas a conductometric indication can still be applied a well known example is the Bonitz titration29 of triethylaluminium (Et3Al) with an azine, such as isoquinoline, for determination of active alkylaluminium in the precatalysts of the Ziegler synthesis of polyethene or polypropene beyond the titration parameter A of the 1 1 complex, the conductivity suddenly decreases,... 

Scheme 9.5 Synthesis of Rh(0) nanoclusters from (1,5-COD)RhP2W15Nb3Oj polyoxoanion-supported nano-cluster-forming precatalyst (space-filling representation). (Adapted from [63].)...

Remarkably, this precatalyst could also be successfully applied in the RCM of several representative diene substrates, allowing the synthesis of essentially all ring sizes greater than four, including mono- and bicyclic compounds, in good to excellent yields, as well as a set of uncommon macrocyclic compounds (representative examples are shown in Scheme 37) [140, 141, 143, 298-300]. 

The first efficient application of a well-defined ruthenium indenylidene complex in metathesis was described in 1999 by Frirstner for the total synthesis of a cyclic prodigiosin derivative, a potential lead compound for the development of immunosuppressive agents. The RCM using the ruthenium indenylidene complex DC (10 mol%) as precatalyst leads to the transformation of the N-protonated diene into the desired macrocycle in 65% yield (Equation 8.8) [43]. 

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