Phosphine-free

Butenoic acid and 4-pentenoic acid (42) react with alkenyl halides or tri-flates to afford 7-alkenyl-7-lactones and the ( -alkenyl-5-valerolactone 44 via the TT-allylpalladium intermediate 43 formed by the elimination of Pd—H and its readdition in opposite regiochemistry using a phosphine-free Pd cata-lyst[43]. 

BU3P. A rapid redox reaction takes place to yield the active Pd(0) species and tributylphosphine oxide. The Pd(0) thus generated is a phosphine-free cata-lyst[341]. Severe reaction conditions are necessary, or no reaction takes place, when Pd2(dba)3 is used in the elimination reaction of cyclic allylic compounds with an excess of -Bu3P[342]. 

Phosphine-Free Ruthenium Precatalysts with One NHC Ligand. 245... 

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. 

Scheme 16 Hoveyda s (left, [49a]) and Blechert s (right, [49b]) synthesis of phosphine-free complex 71a...

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-... 

For the use of a novel phosphine-free ruthenium catalyst with m-bromopyridine ligands [196a] in the CM-based release of azide-protected carbohydrates from a solid support, see Kanemitsu T, Seeberger PH (2003) Org Lett 5 4541... 

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. 

Scheme 1-12 Catalytic Cycle for Phosphine-Free Rh(l) Complexes...

Phosphine Free ligand 5 P (ppm) Yield complex (%) Complex 5 P (ppm)... 

Several optimization studies have been carried out under these phosphine-free conditions. The reaction of bromobenzene and styrene was studied using Pd(OAc)2 as the catalyst, and potassium phosphate and (V,(V-dimethylacetamide (DMA) were found to be the best base and solvent. Under these conditions, the Pd content can be reduced to as low as 0.025 mol %.142 The reaction of substituted bromobenzenes with methyl a-acetamidoacrylate has also been studied carefully, since the products are potential precursors of modified amino acids. Good results were obtained using either N, (V-diisopropylethylamine or NaOAc as the base. 

Low Pd concentrations are beneficial in preventing precipitation of inactive Pd metal.144 Small Pd clusters can be observed in phosphine-free systems,145 and these particles may serve as catalysts or, alternatively, as reservoirs of Pd for formation of soluble reactive species. 

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. 

Although most of the methods for the arylation of enolizable compounds so far developed rely on special phosphine ligands, there is a report of an unusually mild and efficient phosphine-free procedure for the arylation of diethyl malonate, the key to success of which is announced to be the use of a heterogeneous base. In this procedure all three halobenzenes, including PhCl, showed practically identical reactivity (49).198... 

Anionic complexes of boron (boronates, borinates, etc.) have been introduced as convenient reagents in cross-coupling reactions of broad scope, particularly interesting for the transfer of alkynyl and primary alkyl residues, which cannot be accomplished using the standard protocols of the Suzuki-Miyaura reaction. Readily available Ph4BNa can be used as a convenient reagent for phenylation in place of the much more expensive PhB(OH)2, and all four phenyl groups can be utilized when the reaction is carried out with a phosphine-free catalyst in aqueous solutions.244... 

Arylsilanols, silanediols, and triols performed poorly under fluoride activation conditions, but instead required Ag20 (78X274 However, the cross-coupling of arylsilanediols and similar organosilicon reagents (formed in situ from the respective halosilanes) can be achieved under very mild conditions, using phosphine-free catalysts in water in the absence of any organic cosolvents.275... 

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