Titanocene catalyst

Fig. 2. Time-evolution of the methyl/ethyl C-C distances for both the zirconocene and the corresponding titanocene catalyst. The two curves starting at around 3.2 A represent the distance between the methyl carbon atom and the nearest-by ethylene carbon atom in the zirconocene-ethylene and the titanocene-ethylene complex, respectively. The two curves starting at around 1.35 A reflect the ethylene internal C-C bond lengths in the two complexes.

The polymers were converted to supported catalysts corresponding to homogeneous complexes of cobalt, rhodium and titanium. The cobalt catalyst exhibited no reactivity in a Fischer-Tropsch reaction, but was effective in promoting hydroformylation, as was a rhodium analog. A polymer bound titanocene catalyst maintained as much as a 40-fold activity over homogeneous titanocene in hydrogenations. The enhanced activity indicated better site isolation even without crosslinking. 

Although the titanium-based methods are typically stoichiometric, catalytic turnover was achieved in one isolated example with trialkoxysilane reducing agents with titanocene catalysts (Scheme 28) [74], This example (as part of a broader study of enal cyclizations [74,75]) was indeed the first process to demonstrate catalysis in a silane-based aldehyde/alkyne reductive coupling and provided important guidance in the development of the nickel-catalyzed processes that are generally more tolerant of functionality and broader in scope. 

Catalytic enantioselective synthesis of vzc-diols is a challenging issue. Chiral induction using chiral ligands is difficult to achieve. The moderately enantioselective pinacolization of benzaldehyde is demonstrated to be performed by the chiral titanocene catalysts 15 and 16 [42,43]. 

Titanocene catalysts do not catalyze the hydrosilation of most internal olefins, although they can attach active olefins such as styrene, or norbornene to the growing polymer chain ends. The zirconocene-based catalysts, on the other hand, can be powerful hydrosilation catalysts and the remarkable copolymer synthesis shown in Equation 3 can be easily achieved under mild conditions (V7). 

The asymmetric hydrogenation of acyclic imines with the ansa-titanocene catalyst 102 gives the chiral amines in up to 92% ee.684,685 This same system applied to cyclic imines produces the chiral amines with >97% ee values.684,685 The mechanism of these reductions has been studied 686... 

Chien JCW, Babu GN, Newmark RA, Cheng HH, Llinas GH (1992) Microstructure of elastomeric polypropylenes obtained with nonsymmetric ansa-titanocene catalysts. Macromolecules 25 7400-7402... 

Asymmetric hydrogenation of 3,4-hydroisoquinolines with Ir-chiral phosphorus ligand complexes has been studied. Although the highest enantioselectivity to date is obtained with a chiral titanocene catalyst,308,308a 308c chiral BCPM-Ir or BINAP-Ir complexes with additive phthalimide or F4-phthalimide have shown some good selectivity. Some examples are listed in Table 24. 

Racemic 2,5-disubstituted 1-pyrrolines were kinetically resolved effectively by hydrogenation with a chiral titanocene catalyst 26 at 50% conversion, which indicates a large difference in the reaction rate of the enantiomers (Table 21.19, entries 4 and 5), while 2,3- or 2,4-disubstituted 1-pyrrolines showed moderate selectivity in the kinetic resolution (entries 6 and 7) [118]. The enantioselectivity of the major product with cis-configuration was very high for all disubstituted pyrrolidines. The high selectivity obtained with 2,5-disubstituted pyrrolines can be explained by the interaction of the substituent at C5 with the tetrahydroinde-nyl moieties of the catalyst [Eq. (17)]. 

The most selective - and also most general - titanocene catalyst is complex 35 d, also studied by Buchwald and coworkers. This catalyst was used to hydrogenate a variety of functionalized and unfunctionalized cyclic and acyclic alkenes with excellent ee-values in most cases [46]. Enamines could also be hydrogenated with enantiomeric excesses of 80-90% [47]. However, high catalyst loadings (5-8 mol%) and long reaction times were required to drive the reactions to completion. 

The titanocene catalyst 41 was used to hydrogenate a range of aryl-substituted alkenes (Fig. 30.16, Table 30.12) [28]. 

It has been reported that the hydrogenation of imine ArC(Me)=NCH2Ph proceeds with enantioselectivity of up to 96% when Rh(I)-sulfonated BDPP is used in a two-phase system. However, the asymmetric reaction of ON bonds with ruthenium(II) catalyst is rather rare.99 Willoughby and Buchwald100 demonstrated a titanocene catalyst that shows good to excellent enantioselectivity in the hydrogenation of imine. 

Similar success was also achieved by Willoughby and Buchwald100a with a chiral titanocene catalyst. The high ee obtained by Burk and Feaster101a in the asymmetric hydrogenation of 98 was also consistent with the preferred coordination of one isomer forced by the bidentate chelation of the hydrazones. 

Scheme 12.24. Titanocene catalysts used for enantioselective ring-opening of 1.

Titanium white pigments, commercial production of, 19 388 Titanium white rutile pigment, 19 391 Titanium zinc oxide, 5 603 Titanium-zirconium-molybdenum (TZM) alloy, 17 14-15 Titanocene, 25 118 Titanocene catalysts, 16 19 Titanocene dichloride, 25 105 Titanocene synthons, 25 116 Titanocycles, 25 116... 

Scheme 61 Epoxide opening using titanocene catalysts...

Hydrogenation of imines, e.g. 45-48, with a chiral titanocene catalyst at 2000 psig gave the corresponding optically active secondary amines in high enantiomeric excess74. Imines are reduced to amines by trichlorosilane/boron trifluoride etherate in benzene75. 

Hydrogenation of enamines in the presence of a chiral titanocene catalyst yields optically active amines in more than 90% enantiomeric excess, e.g. equation 80220. 

The Brintzinger-type C2-chiral titanocene catalysts efficiently promote asymmetric hydrogenation of imines (Figure 1.30). A variety of cyclic and acyclic imines are reduced with excellent enantioselectivity by using these catalysts. The active hydrogenation species 30B is produced by treatment of the titanocene binaphtholate derivative 30A with n-butyllithium followed by phenylsilane. 

Figure 1.30. Asymmetric hydrogenation of imines with a chiral titanocene catalyst.

Trisubstituted alkenes (1,2-diphenylpropene, 1-methyl-3,4-dihydronaphthalene) have been hydrogenated with excellent optical yields (83-99% ee) in the presence of a chiral bis(tetrahydroindenyl)titanocene catalyst.159... 

Highly enantioselective hydrogenation of geometry-fixed cyclic imines has been achieved by the use of certain chiral Ti and Ir catalysts [14,17]. In particular, a chiral titanocene catalyst developed by Buchwald possess excellent enanti-odifferentiating ability for a variety of cyclic substrates [18]. 

A titanocene catalyst prepared in situ from (R)-3 and -C4H9Li effected the hydrogenation of 2-phenyl-1-pyrroline, a five-membered imine, to give (S)-2-phenylpyrrolidine in 98% ee (Scheme 8) [19]. The reaction proceeded smoothly with an S/C of 1,000. 

Keywords Asymmetric hydrosilylation, optically active alcohols, amines, Chiral Titanocene Catalysts, Acyclic Imines, Cyclic Imines, Chiral Rhodium Catalysts, aromatic ketones... 

Asymmetric hydrosilylation of several AT-alkyl ketimines with PMHS was effectively promoted by the chiral titanocene catalyst (S)-ll (Scheme 8) [24,25], The... 

Racemic N-methylimines derived from 4-substituted 1-tetralones were ki-netically resolved by asymmetric hydrosilylation with phenylsilane (1 equivalent) as a reducing agent using the titanocene catalyst (R)-ll (substrate Ti= 100 1) at 13 °C, followed by a workup procedure to afford the corresponding chiral ketones and chiral cis amines with very high enantio- and diastere-oselectivity (Scheme 12) [28], The extent of the enantiomeric differentiation, kfast/kslow was calculated to be up to 114. The ris-selectivity of this reaction was... 

Several cyclic imines were reduced with phenylsilane as a reducing agent in the presence of the chiral titanocene catalyst 11 followed by a workup process to give the corresponding cyclic amines in excellent ee [26]. The hydrosilylation of 2-propyl-3,4,5,6-tetrahydropyridine with (R)-ll (substrate Ti=100 l) in THF at room temperature was completed in about 6 h (Scheme 14) [29]. The reaction mixture was treated with an acid and then with an aqueous base to afford (S)-coniine, the poisonous hemlock alkaloid, in 99% ee. 

As shown in Scheme 1.30, the chiral titanocene catalyst 34 hydrogenates unfunctionalized, disubstituted styrenes under 136 atm of hydrogen at 65°C to give the saturation products with 83 to >99% ee [156]. A high enantioselectivity is now realized only with aryl-substituted olefins. The enantioselectivity of 41% ee attained 2-ethyl-1-hexene and 34 as catalyst is the highest for hydrogenation of non-aromatic olefins. 

As in asymmetric hydrogenation of olefins and ketones, chiral diphosphine-Rh or -Ir complexes have frequently been used as catalysts [ 1,162,335]. Recently, a chiral titanocene catalyst... 

As shown in Scheme 1.95, the chiral titanocene catalyst 34 (see Scheme 1.10) prepared from 33, n-C4HgLi, andC6H5SiH3 shows a moderate-to-good enantioselectivity in the hydrogenation of /V-benzyl i mines of aryl methyl ketones, whereas the catalytic activity is rather low even at 137 atm [346]. The ketimine with R1 = 4-CH3OC6H4 is hydrogenated with (/ )-34 to give the R amine with 86% ee. The E Z of the imine substrate affects the enantioselection. The optical... 

The chiral titanocene catalyst 34 is very effective for the kinetic resolution of racemic 2,5-disubstituted 1-pyrrolines. When hydrogenation of racemic 5-methyl-2-phenyl-1-pyrroline with (Y)-34 is interrupted at ca. 50% conversion, unreacted R substrate with 99% ee is obtainable with a (2S,5S)-cA-pyrrolidine derivative with 99% ee (Scheme 1.98) [353], As summarized in the table, some other racemic substrates can be resolved in >95% optical yield. 

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