18-electron precatalysts

Figure 7.10 Structures and steric exchange energies (in kcalmoh ) of the 16-electron precatalyst complex and the metallacyclobutanes derived from the...

Increasing the size of the halide was found to increase the rate of initiation for both the first- and second-generation catalyst motifs (Table 9.4). The bromide was made from 1 dibromide by the addition of the l,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene (H2lMes) ligand. The iodides can be made by salt metathesis or exchange via the pyridyl solvates [5]. The larger iodide resulted in a significant increase in the rate of phosphine dissociation, presumably due to increased steric pressure in the 16-electron precatalyst. The iodide complexes... 

Dissociation of PCy3 from the Grubbs first-generation 16-electron precatalyst complex (I-A) proceeds with AE = 21.89 and 25.92 kcal/mol for the second-generation precatalyst (II-A). This is in agreement with the experimental kinetic studies by Grubbs in which AH values of 23.6 0.5 kcal/mol and 27 2 kcal/ mol were obtained for I and II, respectively. 

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. 

More recently, Grubbs et al. obtained a refined mechanistic picture of the initiating step by conducting a 31P NMR spectroscopic study of the phosphine exchange in precatalysts 12-A. These investigations revealed that substitution of the phosphine proceeds via a dissociative-associative mechanism, i.e., a 14-electron species 12-B is involved that coordinates the alkene to give a 16-electron species 12-C (Scheme 12) [26a]. Increased initiation rates are observed if the substituents R and the phosphine ligands PR3 in precatalysts... 

A first evaluation of complex 71a by Blechert et al. revealed that its catalytic activity differs significantly from that of the monophosphine complex 56d [49b]. In particular, 71a appears to have a much stronger tendency to promote cross metathesis rather than RCM. Follow-up studies by the same group demonstrate that 71a allows the cross metathesis of electron-deficient alkenes with excellent yields and chemoselectivities [50]. For instance, alkene 72 undergoes selective cross metathesis with 3,3,3-trifluoropropene to give 73 in excellent yield and selectivity. Precatalyst 56d, under identical conditions, furnishes a mixture of 73 and the homodimer of 72 (Scheme 17) [50a]. While 56d was found to be active in the cross metathesis involving acrylates, it failed with acrylonitrile [51]. With 71a, this problem can be overcome, as illustrated for the conversion of 72—>74 (Scheme 17) [50b]. 

Other precatalysts that are structurally related to 71a have recently been described. Structures and references are given in Table 5. Complex 71c is obviously even more reactive than 71b. The variation in these complexes compared to the parent compound 71a appears to be mainly steric. In contrast, complexes 71d and 71e differ significantly in the electronic properties of the aromatic system. 

The cross metathesis of acrylic amides [71] and the self metathesis of two-electron-deficient alkenes [72] is possible using the precatalyst 56d. The performance of the three second-generation catalysts 56c,d (Table 3) and 71a (Scheme 16) in a domino RCM/CM of enynes and acrylates was recently compared by Grimaud et al. [73]. Enyne metathesis of 81 in the presence of methyl acrylate gives the desired product 82 only with phosphine-free 71a as a pre-... 

Similarly, Kappe and Walla showed that (2-pyridinyl)zinc chloride can be quickly cross-coupled with electron-deficient aryl chlorides using Pd2(dba)3/ t-Bu3P.HBp4 as a precatalyst in THF at 175 °C for 10 min (Scheme 2) [21]. hi a reverse approach, 4-chloropyridine rapidly reacted with (4-methoxyphenyl) zinc chloride (Scheme 2). 

As we have seen from reaction 4.49 donor-acceptor complexes (Lewis- or 7r-type) occur in a fairly inert medium (such as cyclohexane) via charge transfer between a base (electron donor) and an acid (electron acceptor by its electron deficiency). In a few instances, e.g., in the Bonitz titration29 of the precatalyst diethylalaminium chloride with isoquinoline, the complex constists of an ion-pair ionizate. 

The activity of catalytic systems based on imidazolylidene carbenes depends on many factors, among which the most important are likely to be the electronic effects of the ligand and the parameters of complexation. Therefore, the dependence of the performance of such systems on, e.g., the choice of precatalyst is not well understood, as in the following example (Equation (34)) in which two similar ligands behave in exactly the opposite way in the systems based on the presynthesized complex or in situ generation of the catalyst 454... 

In order to vary the electronic situation at the carbene carbon atom a number of carbo- and heterocycle-annulated imidazolin-2-ylidenes like the benzobis(imida-zolin-2-ylidenes) [58-60] and the singly or doubly pyrido-annulated A -heterocyclic carbenes [61-63] have been prepared and studied. Additional carbenes derived from a five-membered heterocycle like triazolin-5-ylidenes 10 [36], which reveals properties similar to the imidazolin-2-ylidenes 5 and thiazolin-2-ylidene 11 [37] exhibiting characteristic properties comparable to the saturated imidazolidin-2ylidenes 7 have also been prepared. Bertrand reported the 1,2,4-triazolium dication 12 [64]. Although all attempts to isolate the free dicarbene species from this dication have failed so far, silver complexes [65] as well as homo- and heterobimetallic iridium and rhodium complexes of the triazolin-3,5-diylidene have been prepared [66]. The 1,2,4-triazolium salts and the thiazolium salts have been used successfully as precatalysts for inter- [67] and intramolecular benzoin condensations [68]. 

Auration proposed in the first mechanism (Scheme 8.8) is possible in similar species, as Kharasch [68] and Fuchita [69] observed in stoichiometric reactions. In both pathways, the same intermediate was formed and no [3-hydrogen elimination was observed and not only furan but other electron-rich arenes could react [70]. Although AuCl3 was the precatalyst used, it was not possible to determine whether Au(III) or Au(I) were the real catalytic species (Scheme 8.9). 

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