Titanocene hydrogenation catalyst

A different situation appears to prevail for the titanocene hydrogenation catalyst studied by Grubbs and coworkers... 

The titanocene dichloride complexes derived from the camphor- and pinene-annulated ligands 126 and 127 were tested as enantioselective hydrogenation catalyst and using 2-phenylbutene as substrate 2-phenylbutane was obtained with ee up to 34% [148, 149]. 

Early transition-metal complexes have been some of the first well-defined catalyst precursors used in the homogeneous hydrogenation of alkenes. Of the various systems developed, the biscyclopentadienyl Group IV metal complexes are probably the most effective, especially those based on Ti. The most recent development in this field has shown that enantiomerically pure ansa zirconene and titanocene derivatives are highly effective enantioselective hydrogenation catalysts for alkenes, imines, and enamines (up to 99% ee in all cases), whilst in some cases TON of up to 1000 have been achieved. 

Whilst hydrogenation catalysts based on early transition metals are as active and selective as those based on late transition metals, they are usually not as compatible with functional groups, and this represents the major difficulty for their use in organic synthesis. Nonetheless, titanocene derivatives have been used in industry to hydrogenate unsaturated polymers. 

Polymer-attached Cp2TiCl2 has been reduced by sodium naphthalide, and the resultant species, which may contain a mixture of Ti(IV), Ti(III), and Ti(II), are more active hydrogenation catalysts for olefins than is the unsupported Cp2TiCl2 (72). Although distinct Ti-H-containing species were not identified, it has been suggested that the complete reaction occurs at one metal center, in contrast to earlier suggestions that such reductions involve a bimolecular reaction of an intermediate titanocene alkyl and a titanocene hydride (30). 

All effective catalysts for the asymmetric reduction of prochiral C=N groups are based on complexes of rhodium, iridium, ruthenium, and titanium. Whereas in early investigations (before 1984) emphasis was on Rh and Ru catalysts, most recent efforts were devoted to Ir and Ti catalysts. In contrast to the noble metal catalysts which are classical coordination complexes, Buchwald s a sa-titanocene catalyst for the enantioselective hydrogenation of ketimines represents a new type of hydrogenation catalyst [6]. In this chapter important results and characteristics of effective enantioselective catalysts and are summarized. 

Titanium complexes that are similar to Duthaler s ( 2.5.2) can be generated from TiCl4, Ti(Or-Pr)4 and diacetoneglucose 1.48. These complexes catalyze asymmetric hetero-Diels-Alder reactions, and give high enantiomeric excesses [827], Corey and coworkers [828] also prepared a chiral titanium catalyst derived from cis-/V-sulfonyl-2-amino-1 -indanol and used this to catalyze asymmetric Diels-Alder reactions. Buchwald and coworkers [829, 830] have proposed the use of titanocene-binaphthol catalysts for asymmetric hydrogenation of imines or trisubsti-tuted olefins. 

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. 

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... 

Deactivation of a homogeneous catalyst by dimerization can usefully be prevented by supporting the monomeric unit [note also that most multicenter catalysts require dissociation to an active monomeric form (/, p. 405 also Section VI)]. This concept has been used to maintain the hydrogenating activity of titanocene intermediates, which normally dimerize to inactive fulvalene complexes (334-336). Similarly maintained... 

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. 

However, the best-researched group of catalysts for these substrates is the metallocenes (Fig. 30.3 Table 30.1, entries 7-13) [7-14]. The highest ee-value was obtained with the chiral samarium metallocene 10a. Hydrogenation of 1 at -78°C gave 2-phenylbutane in 96% ee (Table 30.1, entry 12) [12]. Turnover frequencies (TOFs) as high as 1210 IT1 have been recorded for these catalysts [14]. Catalyst 10 b, the titanocene analogue of 10 a, has been synthesized and used to hydrogenate 1 in 60% ee (Table 30.1, entry 13) [13]. 

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. 

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. 

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