Metathesis phosphine-free

The search for even more active and recyclable ruthenium-based metathesis catalysts has recently led to the development of phosphine-free complexes by combining the concept of ligation with N-heterocyclic carbenes and benzyli-denes bearing a coordinating isopropoxy ligand. The latter was exemplified for Hoveyda s monophosphine complex 13 in Scheme 5 [12]. Pioneering studies in this field have been conducted by the groups of Hoveyda [49a] and Blechert [49b], who described the phosphine-free precatalyst 71a. Compound 71a is prepared either from 56d [49a] or from 13 [49b], as illustrated in Scheme 16. 

Table 5 Phosphine-free ruthenium metathesis catalysts...

Several approaches toward immobilization of phosphine-free ruthenium-based metathesis catalysts bearing a coordinating ether group have been made over the past 3 years [61]. This aspect has been covered in a recently published review by Blechert and Connon [8d] and will therefore not be discussed here. 

An alternative approach to phosphine-free ruthenium precatalysts is based on pyridine complex 70 [48], which has been established by Grubbs et al. as a valuable precursor for other mixed NHC-phosphine complexes (cf. Scheme 15). Complex 70 is only moderately active in the cross metathesis of allylbenzene... 

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-... 

In contrast, substituting the ort/to-methyl groups of SIMes with ortho-fluoride atoms profoundly alters the catalytic metathesis performance. In 2006, Grubbs and co-workers reported the synthesis of the fluorinated NHC-Ru catalysts 25 and 26 [41] (Fig. 3.8). Catalytic tests in the RCM of 1 to form 2 showed that the phosphine-free catalyst 26 was slower than the standard catalyst 16, which was consistent with theoretical investigations suggesting the electron-withdrawing fluoride atoms would lead to a decrease in catalyst activity [42]. However, in contrast to the computational... 

Despite those challenges, both Johnson [161] and Grela [162] performed several cross metathesis reactions with vinylhalides using phosphine free catalysts. Turnover numbers (TON) above 20 were very few, while in many cases the TON stayed below ten. The diastereoselectivity of CMs with vinylhalides is shghtly in favour of the Z product which is similar to their acrolein-counterparts. 

The synthesis and olefin metathesis activity in protic solvents of a phosphine-free ruthenium alkylidene bound to a hydrophilic solid support have been reported. This heterogeneous catalyst promotes relatively efficient ring-closing and cross-metathesis reactions in both methanol and water.200 The catalyst-catalyzed cross-metathesis of allyl alcohol in D20 gave 80% HOCH2CH=CHCH2OH. 

Synthesis and Metathesis Reactions of a Phosphine-Free Dihydroimidazole Carbene Ruthenium Complex, S. Gessler,... 

A family of phosphine-free ruthenium-based olefin metathesis catalysts has been developed over the last few years. First, work done independently by Hoveyda and Blechert resulted in the H2Mes isopropoxybenzylidene (4b), a highly active air-stable ruthenium (pre)catalyst for olefin metathesis (Scheme 4). Hoveyda described (4b) as a recyclable monomeric catalyst also with high activity for ring-opening, ring-closure, and cross metathesis that tolerates... 

Scheme 4 Phosphine-free ruthenium complexes for olefin metathesis...

Blechert has used a water compatible support for a metathesis catalyst [57]. The support swells with water and allows ring-dosing metathesis to be carried out in aqueous media. The commercially available PEGA-NH2 (Structure 20) resin was functionalized and connected to a phosphine free metathesis catalyst to prepare heterogeneous complex 21. 

Domino metathesis reactions of the dienynes 97 and 99 catalyzed by the phosphine-free ruthenium catalyst 4 in the presence of ethylene allowed a rapid access to the naturally occurring marine trisnorsesquiterpenes (—)-clavukerin A (98) and (—)-isoclavukerin A (100), respectively, by preferential initiation at the disubstituted alkene (Scheme 2.36) [18i]. As the dienyne substrates 97 and 99 were easily available from (S)- and (J )-citronellal, respectively, in only three high yielding operations, the 1,3-dienes 98 and 100 now offer themselves as enantiopure building blocks for the preparation of structurally more complex hydroazulene targets. 

Scheme 2.38 depicts a relay dienyne metathesis transformation to afford the hydroazulene ring system [18m]. In the presence of the phosphine-free catalyst 6, substrate 103 used as an epimeric mixture underwent a completely regioselective domino cyclization due to exclusive attack of the ruthenium carbene at the terminal olefin followed by RCM with release of 2,5-dihydrofuran. Diastereomer 104 was then further elaborated to achieve a formal synthesis of the guaiane (—)-englerin A, which shows a highly selective action against renal cancer cell lines. 

Enyne metathesis can also be combined with an intramolecular Diels-Alder reaction (IMDA) in a domino manner [35]. Reaction of the dienes 172 with the terminal alkynes 173 in the presence of the phosphine-free catalyst 4 at reflux temperature yielded the carbobicyclic products 174 preferentially via an exo-(E)-anti or endo-(2)-anti transition state for the [4- -2]-cycloaddition step, respectively (Scheme 2.60) [35a[. 

Similarly, Fischer carbene complexes are formed when Grubbs systems react with vinyl esters, vinyl carbonates, and vinyl halides. However, these Fischer car-benes are known to decompose to give terminal ruthenium carbide species by elimination of HX (X = OjCR, OjCOR, halide) [83-86]. Notably, the formation of the carbide complexes is less favorable in phosphine-free systems, which enables the Hoveyda [56] and Piers [87] catalysts to promote the cross metathesis of vinyl hahdes and terminal or internal olefins [88]. 

Figure 11.4 Phosphine-free second-generation ruthenium-based metathesis catalysts.

Stability (Figure 11.7) [60]. RCM of the standard substrate 17 using this complex showed complete conversion in 15 min, while the complexes 10 and 2 showed 92 and 85% conversions, respectively, under the same conditions. Subsequendy, the groups of Wagener, Mol, and Fiirstner reported the synthesis and metathesis activity of the tricyclohexylphosphine containing 38 and phosphine-free 39 (an analog of complex 37) [61-63]. In the self-metathesis of 1-octene, catalyst 38 displayed TONs six times larger (TON >640 000) and initial TOFs 20 times faster than those of 10 at ambient temperature, and an even better performance at elevated temperatures [62]. 

Despite the decreased steric protection, these complexes (particularly the phosphine-free) were found to be unexpectedly robust and fairly active for all types of olefin metathesis reactions. Increasing the size of the ortho substituents on the Al-aryl group from H to Ft resulted in increased stability however, further increase of the steric bulk resulted in slower catalyst initiation. 

Gessler, S., Randl, S., Blechert, S., Synthesis and metathesis reaetions of a phosphine-free dihydroimidazole carbene ruthenium complex. Tetrahedron Lett. 2000,41 9973-9976. 

PHOSPHINE-FREE EWG-ACIWATED RUTHENIUM OLEFIN METATHESIS CATALYSTS DESIGN, PREPARATION, AND APPLICATIONS... 

Phosphine-free EWG-activated ruthenium olefin metathesis eatalysts... 

It seems that palladium complexes with high oxidative states and basic ligands can be involved in oxidative addition as weU as in o-bond metathesis. Cheng has demonstrated that phosphine-free Pd complexes together with alkenyl or aryl iodides are very efficient catalysts for 1,2-diboration of allenes. This reaction is completely regioselective and highly... 

Ring-closing enyne metathesis of 159 generated an intermediate ruthenium carbene which participated in a subsequent cross-metathesis reaction with methyl vinyl ketone to generate the seven-membered carbocycle and ( )-conjugated dienone subunit 162 in a single synthetic transformation. Specifically, treatment of enyne 159 with methyl vinyl ketone 160 in the presence of catalyst 162 (20mol%) provided (+)-8-epi-Xanthatin in 83% yield. It should be noted that the phosphine-free ruthenium catalyst 162 was employed in this step because it had been reported to be superior as a catalyst in tandem RCM-CM reactions reported previously. 

Gessler S, Randl S, Wakamatsu H, Blechert S. Highly selective cross metathesis with acrylonitrile using a phosphine free Ru-complex. Synlett 2001 430-432. 

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