Asymmetric hydrogenation titanocene

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... 

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. 

Broene and Buchwald37 synthesized chiral titanocene compound 22 for the asymmetric hydrogenation of trisubstituted olefins. 

TABLE 6-3. Chiral Titanocene-Catalyzed Asymmetric Hydrogenation of Unfunctionalized Trisubstituted Olefins... 

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. 

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.

We note that there are NMR-based kinetic studies on zirconocene-catalyzed pro-pene polymerization [32], Rh-catalyzed asymmetric hydrogenation of olefins [33], titanocene-catalyzed hydroboration of alkenes and alkynes [34], Pd-catalyzed olefin polymerizations [35], ethylene and CO copolymerization [36] and phosphine dissociation from a Ru-carbene metathesis catalyst [37], just to mention a few. 

SCHEME 78. Titanocene-catalyzed asymmetric hydrogenation of imines. 

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... 

Asymmetric hydrogenation of Scheme 1.101 provides a general route to isoquinoline alkaloids (see Section 1.3.1.1). An imine substrate is hydrogenated with the chiral titanocene (/ )-34 to give the S product with 98% ee [346a,b,352], A neutral BCPM-Ir complex with phthalimide in toluene also shows high enantioselection [358]. The choice of a weakly polar... 

Asymmetric hydrogenation has been reported to occur in excellent yield and ee when a trisubstituted alkene is hydrogenated with a chiral titanocene catalyst (equation 84)334. A similar reaction, but with variable enantioselectivity, may also be obtained with chiral Rh, Ru and Co catalysts335-338. Disubstituted alkenes (mainly 1,1-disubstituted) may also be... 

Other Reactions of Chiral Titanocene Derivatives. Buch-wald has recently reported the catalytic asymmetric hydrogenation of imines and unfunctionalized alkenes using chiral titanocene catalysts. 

The first example of catalytic asymmetric hydrogenation of N,N dialkyl enamines was reported by Buchwald and Lee in 1994. By using 5 mol% chiral ansa titanocene catalyst [(S,S,S) (EBTHI)TiO binaphtho] (EBTHI = ethylenebis(tetrahydroindenyl)), they achieved excellent enantioselectivities (up to 98% ee) in the hydrogenation of (1 arylvinyl)amines [50]. In 2000, Boner used chiral rhodium diphosphine complexes for the hydrogenation of 2 N piperidinylethylbenzene and 2 alkyl 1,3,3 trimethyle neindoline and obtained the tertiary amines in moderate enantiomeric excesses [51]. 

A chiral zw a-metallocene triflate complex catalyzes the Diels-Alder cycloaddition reaction between an oxazolidinone-based dienophile and cyclopentadiene [206]. Triflate in titanocene and zirconocene complexes is labile [207,208] and thus the polarity of solvent influences the reactivity and enantioselectivity. Asymmetric hydrogenation of imines and enamines catalyzed by chiral aw a-titanocene catalyst provides amines with high enantioselectivity [209,210]. 

Keywords Asymmetric hydrogenation. Simple olefins. Unfunctionalized olefins. Chiral metallocenes, Chiral phosphines, Rhodimn, Ruthenimn, Chiral titanocenes. Chiral zirconocene. Chiral cyclopentadienyUanthanides, Phosphanodihydrooxazole, Iridium, 2-Phenyl-l-butene... 

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 asymmetric hydrogenation of imines usually yields disappointing results. However, Willoughby and Buchwald have recently obtained high enantiomeric excesses in hydrogenations of imines in the presence of a titanocene catalyst. The most useful results are obtained from cyclic imines [830, 1143, 1144],... 

A titanocene catalyst bearing a chiral fused cyclopentadienyl ligand has been proposed by Vollhardt and coworkers [1334] for asymmetric hydrogenation of 2-phenyl-1 -butene, high ee are obtained at -75°C. 

A binaphthol titanocene catalyst has been proposed by Buchwald and Broene for use in asymmetric hydrogenation of nonfimctionalized trisubstituted olefins [829], These reactions take place undo- H2 pressure at 65°C. Acydic or cyclic olefins lead to saturated, branched alkanes with high chemical yield and enantiose-lectivity (ee 83 - 99%). Unfortunately, in most of the cases, the absolute configuration of the product has not yet been determined. 

Three classes of catalysts have been studied for the asymmetric hydrogenation of imines. One class of catalyst is generated from late transition metal precursors and bisphosphines. These catalysts have typically been generated from rhodium and iridium precursors. A second class of catalyst is based on the chiral titanocene and zirconocene systems presented in the previous section on the asymmetric hydrogenation of unfunctionalized olefins. The third class of catalyst is used for the transfer hydrogenation of imines and consists of ruthenium or rhodium complexes containing diamine, amino tosylamide, or amino alcohol ligands. " ... 

The basic compound of Brintzinger s ansa-titanocene complexes is ethylenebis-(tetrahydroindenyl)titanium dichloride, (EBTHI)TiCl2. Further analogues ((EBTHI)TiH, (EBTHI)Ti(Me)2, and (EBTHI)Ti(CO)2) have been wddely used for asymmetric hydrogenation, hydrosilylation, and Pauson-Khand reaction (121). Novel optically active titanium complexes containing a linked amido-cyclopentadienyl ligand have been developed and used for asymmetric hydrogenation (122). 

Titanium, Zirconium, Hafnium - The catalytic asymmetric hydrogenation of imines has been reported using a chiral titanocene catalyst. " An enantiopure titanocene catalyst has been used in the catalytic asymmetric hydrogaution of disubstituted enamines. Kinetic resolution of a racemic disubstituted pyrroline has been effected by asymmetric reduction with a chiral titanocene catalyst. Poly(methylhydrosiloxane) has been used as a stoichiometric... 

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. 

Finally, carbohydrate ligands of enantioselective catalysts have been described for a limited number of reactions. Bis-phosphites of carbohydrates have been reported as ligands of efficient catalysts in enantioselective hydrogenations [182] and hydrocyanations [183], and a bifunctional dihydroglucal-based catalyst was recently found to effect asymmetric cyanosilylations of ketones [184]. Carbohydrate-derived titanocenes have been used in the enantioselective catalysis of reactions of diethyl zinc with carbonyl compounds [113]. Oxazolinones of amino sugars have been shown to be efficient catalysts in enantioselective palladium(0)-catalyzed allylation reactions of C-nucleophiles [185]. 

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. 

---