Precatalyst Activation and Catalysis

Sharpless et al. coined the word ligand-accelerated catalysis (LAC), which means the construction of an active chiral catalyst from an achiral precatalyst via ligand exchange with a chiral ligand. By contrast, a combinatorial library approach in which an achiral pre-catalyst combined with several chiral ligand components (L, L, —) may selectively assemble in the presence of several chiral activators (A, A, —) into the most catalytically active and enantioselective activated catalyst (ML A" ) (Scheme 8.16). ... 

The chiral precatalyst is a titanium species. It is generated by the in situ treatment of titanium isopropoxide with diethyl or diisopropyl tartarate. The relative amounts of Ti(OPr )4 and the tartarate ester have a major influence on the rate of epoxidation and enentioselectivity. This is because the reaction between Ti(OPr )4 and the tartarate ester leads to the formation of many complexes with different Ti tartarate ratios. All these complexes have different catalytic activities and enantioselectivities. At the optimum Ti tartarate ratio (1 1.2) complex 9.35 is the predominant species in solution. This gives the catalytic system of highest activity and enantioselectivity. The general phenomenon of rate enhancement due to coordination by a specific ligand, with a specific metal-to-ligand stoichiometry, is called ligand-accelerated catalysis. 

By applying a new mode of cooperative catalysis involving the combination of a chiral Bronsted acid and a -symmetric biaryl saturated imidazolium precatalyst, Lee and Scheldt disclosed a highly enantioselective NHC-cata-lyzed [3 + 2] annulation reaction between a,p-alkynals and a-keto esters to generate the desired y-crotonolactones in high yields and excellent levels of enantioselectivity (up to 92% yield, 92% ee). The authors proposed that NHC-bound allenolate underwent addition to the a-keto ester activated by the chiral Bronsted acid derived co-catalyst (Scheme 7.43). 

Plenio has developed an alternative way in which to treat concentration/ time data from RCM reactions mediated by Hoveyda-type complexes. The authors conducted a series of kinetic experiments (at 303—323 K in toluene-dg) using a range of precatalysts, at different concentrations, and with different precatalyst loadings. Using a detailed and a priori mathematical approach, the authors successfully separated values for rate constants for activation (kaci), catalysis (fe t) and decomposition (fejec), showing that each was concentration-independent (Eqn (2.21)). 

Apart from catalysis with well-defined iron complexes a variety of efficient catalytic transformations using cheap and easily available Fe(+2) or Fe(+3) salts or Fe(0)-carbonyls as precatalysts have been pubhshed. These reactions may on first sight not be catalyzed by ferrate complexes (cf. Sect. 1), but as they are performed under reducing conditions ferrate intermediates as catalytically active species cannot be excluded. Although the exact nature of the low-valent catalytic species remains unclear, some of these interesting transformations are discussed in this section. 

Under all the conditions studied, addition of bare Si02-SH to Heck or Suzuki coupling reactions using a variety of bases, aryl halides and solvents resulted in complete cessation of the catalytic activity (35). These results suggest that catalysis with this precatalyst is also associated with labile palladium species that... 

Active catalyst species or catalysis intermediates can often be trapped by stoichiometric reactions of the precatalyst with the substrate. The following example describes the successful isolation of such an intermediate with participation of Ln-O cr-bonds. Reduction processes mediated by low oxidation states of the lanthanide elements are of special interest in organic synthesis [256]. One of the most intensively studied reactions is the stoichiometric reduction of arylketones by rare earth metals ytterbium and samarium [277]. Thus formed dianions possess high nucleophilic character and excess lanthanide metal can even accomplish complete cleavage of the C-O double bond (Scheme 36). 

In contrast, the Shell process for MMA operates under milder conditions (60°C, 10-60 bar), and the mechanism at a molecular level is better understood. The reaction is usually carried out in methanol, which acts both as a solvent and as a reactant. The precatalyst is Pd(OAc)2, which is mixed with an excess of phosphine ligand to generate the active catalytic intermediates in situ. An important requirement for efficient catalysis is the presence of an acid HX that acts as a co-catalyst. 

First attempts of an asymmetric Stetter reaction were made 1989 in our research group with the investigation of chiral thiazolium salts such as 136 as precatalysts. The reaction of n-bu Lanai (133) with chalcone (134) in a two-phase system gave the 1,4-diketone 135 with an enanan-tiomeric excess of 39%, but a low yield of only 4% (Scheme 37) (Tiebes 1990 Enders 1993 Enders et al. 1993b). The catalytic activity of thiazolium as well as triazolium salts in the Stetter reaction persisted at a rather low level. Triazolium salts have been shown to possess a catalytic activity in the non-enantioselective Stetter reaction (Stetter and Kuhlmann 1991), but in some cases stable adducts with Michael acceptors have been observed (Enders et al. 1996a), which might be a possible reason for their failure in catalysis. 

Apart form a great number of chiral NHC carbenes that have been used as ligands in enantioselective transition-metal catalysis (Gade and Bellemin-Laponnanz 2007), some less usual heterazolium salts have been tested in organocatalytic transformations. A planar-chiral thia-zolium salt (Pesch et al. 2004) and a rotaxane-derived precatalyst were reported (Tachibana et al. 2004), as well as catalytically active peptides containing an unnatural thiazolium-substituted alanine amino acid (Fig. 3 Mennen et al. 2005a,b). 

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