Low catalyst loading

Yield for the process at low catalyst loading is 95%. AJ-Methyl-toluenediamiae, one of the reaction by-products, represents not only a reduction ia yield, but also a highly objectionable impurity ia the manufacture of toluene diisocyanate. Low concentrations of CO (0.3—6% volume) control this side reaction. 

The principle cost determinant in typical hydrolytic or phenolic resolutions is the cobalt catalyst, despite the relatively low catalyst loadings used in most cases and the demonstrated recyclability with key substrates. From this standpoint, recently developed oligomeric (salen)Co complexes, discussed earlier in this chapter in the context of the hydrolytic desymmetrization of meso-epoxides (Scheme 7.16), offer significant advantages for kinetic resolutions of racemic terminal epoxides (Table 7.3) [29-31]. For the hydrolytic and phenolic kinetic resolutions, the oligo-... 

The cyclopentadienyl triflate complexes of zirconium and titanium 51 and 52 (Figure 3.7) are also active catalysts [51]. Their activity has been tested in a wide variety of dienes and dienophiles. It is noteworthy that even at low catalyst loadings, rate accelerations between 10 and > 10 times have been observed. No special precautions were taken to dry the solvents or the substrates, in contrast with the traditional Lewis acids which require either predried solvents or high catalyst loadings. 

Very recently Page and coworkers have reported the D KR of sec-amines using a low catalyst loading of an Ir complex for the racemization, and Candida rugosa lipase for the enzymatic resolution [38]. 

A wealth of other regular, mainly metallic structures has been reported. Many of them are derived from static mixers. A general comment has to be made that the relatively low catalyst loading often makes them impractical for processes occurring... 

In the majority of the known examples, the donor of hydrogen equivalents is isopropanol HCOO" or HCOOH/EtjN azeotrope are less successful. Aromatic ketones (mainly acetophenone and benzophenone) were the easiest to reduce even under mild conditions and low catalyst loadings. 

The asymmetric 1,4-conjugate addition of phenyl boronic acids to cyclohex-2-enone was catalysed by the Pd complex 141 (Fig. 2.25). Good to excellent yields and high ee (90-97%) were obtained under mild conditions and low catalyst loadings (rt, 3 mol%)... 

Preformed complexes of type 52, 53 and 59, and in situ catalyst systems based on IMesX (X = CO, MeS03H, HCl, HBr, HI) and IPrHCl, have been tested for telomerisation of butediene with primary and secondary amines. Under optimised conditions, and low catalyst loadings, excellent activities and selectivities were observed [82]. 

Pyridine compounds 45 can also be produced by the NHC-Ni catalysed cycloaddition between nitriles 43 and diynes 44 (Scheme 5.13) [16]. The SIPr carbene was found to be the best ligand for the nickel complex in this reaction. The reaction required mild reaction conditions and low catalyst loadings, as in the case of cycloaddition of carbon dioxide. In addition to tethered aUcynes (i.e. diynes), pyridines were prepared from a 3-component coupling reaction with 43 and 3-hexyne 23 (Scheme 5.13). The reaction of diynes 44 and nitriles 43 was also catalysed by a combination of [Ni(COD)J, NHC salts and "BuLi, which generates the NHC-Ni catalyst in situ. The pyridines 45 were obtained with comparable... 

With these catalysts, di- and even some tri-ort/io-substituted products could be formed using very low catalyst loading (50 ppm - 0.05 mol%). Some representative examples of the products prepared are shown in Scheme 6.26 [105]. 

However, modification of the allyl fragment by substitution of one of the terminus positions has provided more active complexes by enabling a more facile activation step [159], This allows the coupling of highly hindered amines with hindered aryl chlorides at room temperature and with low catalyst loadings [160] (Scheme 6.48). 

Further studies by Bode and co-workers have shown that enolate formation from a-chloroaldehydes and subsequent reaction with 4-oxo-enoates or unsaturated a-ketoesters 232 generates dihydropyranones 233 in excellent diastereo- and enantio-selectivities, and with impressively low catalyst loadings [90], This work has been extended to the generation of enolate equivalents from bisulfite adducts of a-haloaldehydes 234 under aqueous conditions (Scheme 12.50) [91]. 

Similar reactions have been developed more recently by Jin et al. using chiral amino thioacetate ligands derived from the corresponding amino alcohols. Low catalyst loadings of only 1-2.5 mol% were sufficient to achieve excellent enantioselectivities of up to 98% ee as well as high conversions in short times (Scheme 3.61). These authors have shown that the thioacetoxy moiety of the amino thioacetates has a surprisingly beneficial effect in enhancing the asymmetric induction. 

It was independently found by two groups that the exo-diol derived from bis(camphorsulfonyl)-substituted tra .s-cyclohexane-1,2-diamine ligand (HOCSAC) was an excellent promoter for the enantioselective addition of dialkyIzinc reagents to any type of ketones, even dialkyl ketones, in the presence of Ti(Oi-Pr)4. As shown in Scheme 4.11, excellent enantioselectivities of up to 99% ee were obtained in these conditions in combination with high yields and with a low catalyst loading of 2-10 mol%. 

The deleterious effects of catalyst poisoning when carrying out asymmetric hydrogenations at low catalyst loading caimot be overemphasised. In order to eliminate the possibility that the substrate synthesis introduced inhibitory impurities, an alternative synthetic protocol was examined (Scheme 7.4). The use of a brominating agent and an expensive palladium catalysed step in the initial route could limit the development of this as an economically favourable process and this was further motivation to examine alternative routes to the hydrogenation substrate. 

With all other pieces of the synthesis in place our attention now focused on the final piece in the jigsaw-the asymmetric hydrogenation of the amide enamide 42. Screening of hydrogenation conditions rapidly led to identification of a number of conditions which allowed the desired hydrogenation to proceed at low catalyst loadings and in non-chlorinated solvents (Table 9.9). 

A tremendous amount of progress has been made over the past decade in the understanding of the catalyzed reductive coupling of unactivated alkenes and alkynes. Both early and late transition metal complexes accomplish the reaction with good yields and with low catalyst loadings. Enynes and dienes can... 

Addition of HSiMeCl2 to cyclopentadiene is catalyzed by (42) at room temperature at low catalyst loading (0.01 mol.%) to give the (S)-allylsilane in moderate ee.125 This enantioselectivity can be enhanced dramatically with incorporation of perfluoroalkyl groups into the amine functionality (Scheme 26).126... 

Selected coupling reactions of aryl chlorides in the presence of Pd/1 are shown in Scheme 4. For example, nonactivated and sterically hindered 2,6-dimethylchlorobenzene reacts with bulky, sterically congested anilines smoothly at low catalyst loading (0.5 mol% Pd(OAc)2/l P/Pd = 2 1). 

Du Bois originally used rhodium(n) acetate and rhodium triphenylacetate (tpa) as catalysts and found that regio-and diastereocontrol was influenced by the catalysts, but neither was particularly effective when low catalyst loadings were used. Inspired by the bridged dirhodium catalysts which have been developed for carbenoid chemistry,40,273,274 a second generation catalyst Rh2(esp)2 116 (esp = a,a,a, o -tetramethyl-l,3-benzenedipropionate) was designed which was capable of much higher turnover numbers (Scheme ll).275 Furthermore, this catalyst was effective in intermolecular reactions. 

Pd(acac)2 has been reported to be an active catalyst in soybean oil hydrogenation [47]. The reactions were conducted in bulk with low catalyst loadings (1-60 ppm) and without any co-catalyst. Under 10 atm H2 pressure and at 80-120 °C, optimum linolenate selectivity and high trans-isomers content were obtained. Decomposition of the catalyst occurred at temperatures above 120 °C. 

These Mo catalysts with a C2-tether connecting the phosphine and cyclopenta-dienyl ligand provide an example of the use of mechanistic principles in the rational design of improved catalysts, in this case based on information about a decomposition pathway for the prior generation of catalysts. The new catalysts offer improved lifetimes, higher thermal stability, and low catalyst loading. The successful use of a triflate counterion and solvent-free conditions for the hydrogenation are additional features that move these catalysts closer to practical utility. 

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