Titanium catalysts reactions

Yamamoto et al. have reported a chiral helical titanium catalyst, 10, prepared from a binaphthol-derived chiral tetraol and titanium tetraisopropoxide with azeotropic removal of 2-propanol [16] (Scheme 1.22, 1.23, Table 1.9). This is one of the few catalysts which promote the Diels-Alder reaction of a-unsubstituted aldehydes such as acrolein with high enantioselectivity. Acrolein reacts not only with cyclo-pentadiene but also 1,3-cyclohexadiene and l-methoxy-l,3-cyclohexadiene to afford cycloadducts in 96, 81, and 98% ee, respectively. Another noteworthy feature of the titanium catalyst 10 is that the enantioselectivity is not greatly influenced by reaction temperature (96% ee at... 

C, 92% ee at -20 °C, 88% ee at 0°C in the reaction of acrolein and cyclopen-tadiene). This is unusual for metal-catalyzed asymmetric reactions, with only few similar examples. The titanium catalyst 10 acts as a suitable chiral template for the conformational fixing of a,/ -unsaturated aldehydes, thereby enabling efficient enantioface recognition, irrespective of temperature. 

The Diels-Alder reaction catalyzed by this chiral titanium catalyst 31 has wide generality (Scheme 1.53, 1.54, Table 1.22, 1.23). Acryloyl- and fumaroyl-oxazolidinones react with isoprene giving cycloadducts in high optical purity. 2-Ethylthio-l,3-buta-diene can also be successfully employed as the diene [42]. 

Among the many chiral Lewis acid catalysts described so far, not many practical catalysts meet these criteria. For a,/ -unsaturated aldehydes, Corey s tryptophan-derived borane catalyst 4, and Yamamoto s CBA and BLA catalysts 3, 7, and 8 are excellent. Narasaka s chiral titanium catalyst 31 and Evans s chiral copper catalyst 24 are outstanding chiral Lewis acid catalysts of the reaction of 3-alkenoyl-l,2-oxazolidin-2-one as dienophile. These chiral Lewis acid catalysts have wide scope and generality compared with the others, as shown in their application to natural product syntheses. They are, however, still not perfect catalysts. We need to continue the endeavor to seek better catalysts which are more reactive, more selective, and have wider applicability. 

The effect of the metals used was then examined (Table 5.4). When the group 4 metals, titanium, zirconium, and hafnium, were screened it was found that a chiral hafnium catalyst gave high yields and enantioselectivity in the model reaction of aldimine lb with 7a, while lower yields and enantiomeric excesses were obtained using a chiral titanium catalyst [17]. 

A quite different type of titanium catalyst has been used in an inverse electron-demand 1,3-dipolar cycloaddition. Bosnich et al. applied the chiral titanocene-(OTf)2 complex 32 for the 1,3-dipolar cycloaddition between the cyclic nitrone 14a and the ketene acetal 2c (Scheme 6.25). The reaction only proceeded in the presence of the catalyst and a good cis/trans ratio of 8 92 was obtained using catalyst 32, however, only 14% ee was observed for the major isomer [70]. 

It was our delight that the reactions catalyzed were activated even at -40 °C in the presence of a catalytic amount of achiral titanium catalysts (10 mol%) to afford the desilylacetylated 2-pyrazoline cycloadduct Na, l-acetyl-4-methyl-5-(2-oxo-3-oxazolidinylcarbonyl)-2-pyrazoline, in high yields as the far major product (Scheme 7.35). Although some chiral titanium TADDOlate catalysts were successfully applied to activate these reactions leading to the moderate enantioselectivities (up to 55% ee), the chemical yields were not satisfactory. 

Diphenol carbonate is produced by the reaction of phosgene and phenol. A new approach to diphenol carbonate and non-phosgene route is by the reaction of CO and methyl nitrite using Pd/alumina. Dimethyl carbonate is formed which is further reacted with phenol in presence of tetraphenox titanium catalyst. Decarbonylation in the liquid phase yields diphenyl carbonate. 

The decomposition is significantly accelerated and the temperature of the first decomposition reaction is lowered to 120°C (Fig. 19.7). The decomposition rate is relatively low compared with other titanium-based dopants. The highest activity of a titanium catalyst used in alanate decomposition was observed for ligand-stabilized colloidal titanium metal [42]. 

Hydroalumination of terminal alkenes using EtjAl as the hydride source must be carried out with titanium catalysts [24], since zirconium compounds lead to the formation of alumacyclopentanes [60, 61] (Scheme 2-11) and carbometallated products [62]. Suitable substrates for hydroalumination include styrene, allylnaphthalene and vinylsilanes. Only one of the ethyl groups in EtjAl takes part in these reactions, allowing the synthesis of diethylalkylalanes, which are difficult to obtain by other methods. 

Scheme 2.9 gives some examples of use of enantioselective catalysts. Entries 1 to 4 are cases of the use of the oxazaborolidinone-type of catalyst with silyl enol ethers and silyl ketene acetals. Entries 5 and 6 are examples of the use of BEMOL-titanium catalysts, and Entry 7 illustrates the use of Sn(OTf)2 in conjunction with a chiral amine ligand. The enantioselectivity in each of these cases is determined entirely by the catalyst because there are no stereocenters adjacent to the reaction sites in the reactants. 

Finally, the discovery of exceptionally efficient catalysts for solvent-free enantioselective hetero-Diels-Alder reactions was made possible by a combinatorial approach.121 The object was to find a chiral titanium catalyst for the reaction of aldehydes (51) with Danishefsky s diene (91), with formation of cycloadduct (92) in >99% enantipurity (Equation (11)). 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

A number of additional metal-catalyzed epoxidations have been reported in the past year. Platinum is a rarely used catalyst in oxidation reactions. The use of chiral Pt-catalyst 2 in the epoxidation of terminal alkenes provides the epoxide products in moderate yield and enantiomeric excess <06JA14006>. The chiral hydroxamide 3 is used with a Mo catalyst to provide the epoxide product in excellent yields and moderate enantioselectivity <06AG(I)5849>. A bis-titanium catalyst, 4, has also been used to epoxidize the usual set of alkenes with H202 as the oxidant <06AG(I)3478>. 

Mikami and co-workers16-19 have done extensive work for developing catalysts for the asymmetric carbonyl-ene reaction. Excellent enantioselectivites are accessible with the binol-titanium catalyst 17 (Equation (10)) for the condensation of 2-methyl butadiene (R1 = vinyl) and glyoxalates (binol = l,T-binaphthalene-2,2 -diol).16 The products were further manipulated toward the total synthesis of (i )-(-)-ipsdienol. The oxo-titanium species 18 also provides excellent enantioselectivity in the coupling of a-methyl styrene with methyl glyoxalate.17 Reasonable yields and good enantioselectivites are also obtained when the catalyst 19 is formed in situ from titanium isopropoxide and the binol and biphenol derivatives.18... 

MP borohydride catches one equivalent of the titanium catalyst, while the polystyrene-bound diethanolamine resin (PS-DEAM) can scavenge the remaining titanium catalyst. The borohydride reagent also assists in the reductive animation reaction. Final purification of the crude amine product is achieved with a polystyrene-bound toluene sulfonic acid resin scavenger that holds the amine through an ion exchange reaction, while impurities are washed off. The pure amine can be recovered with methanol containing 2M ammonium hydroxide. 

The self-assembly of a chiral Ti catalyst can be achieved by using the achiral precursor Ti(OPr )4 and two different chiral diol components, (R)-BINOL and (R,R)-TADDOL, in a molar ratio of 1 1 1. The components of less basic (R)-BINOL and the relatively more basic (R,R)-TADDOL assemble with Ti(OPr )4 in a molar ratio of 1 1 1, yielding chiral titanium catalyst 118 in the reaction system. In the asymmetric catalysis of the carbonyl-ene reaction, 118 is not only the most enantioselective catalyst but also the most stable and the exclusively formed species in the reaction system. 

Chiral titanium catalyst for asymmetric Diels-Alder reactions. A Japanese group2 recently reported that a chiral titanium reagent (1), prepared in situ from TiCl2(0-f-Pr)2 and the chiral diol 2, derived from L-tartaric acid, in combination... 

Titanium catalysts have long been used in electron transfer reactions involving epoxides, mostly as stoichiometric reagents. Gansauer et al. have developed a catalytic version of these reactions using titanocenes along with zinc metal to generate the active catalyst (Scheme 60). In situ reduction of Ti(IV) with zinc metal provides Ti(III) species 231, which coordinates... 

The ability of titanium-grafted silicas in catalyzing the epoxidation with TBHP of fatty compounds was first tested on two pure Qg monounsaturated FAMEs methyl oleate (ds-9-octadecenoate Scheme 12.1) and methyl elaidate (trans-9-octadecenoate) [49]. In both cases, selectivity to 9,10-epoxystearate was very high (>95%) and the reaction was fully stereospecific, confirming that epoxidation with titanium catalysts and TBHP proceeds via a non-radical mechanism with retention of configuration at the C=C bond. Ti-MCM-41 was more active than Ti-SiC>2 (Fig. 12.1). Actually, methyl oleate was almost completely converted after... 

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