Calcium catalysts, asymmetric

Kumaraswamy et al. reported asymmetric 1,4-addition reactions using chiral calcium complexes prepared from calcium chloride and dipotassium salt of BINOL or Hg-BESfOL (5,5, 6,6, 7,7, 8,8 -octahydro-l,l -bi-2-naphthol) [42-45]. After optimization of the calcium salts and reaction conditions, the calcium catalyst was successfully applied to asymmetric 1,4-additions of malonates or p-ketoesters to a,p-unsaturated carbonyl compounds (Tables 4 and 5) [42, 44]. Among the a,p-unsaturated carbonyl compounds employed in the reactions with malonates, cyclopentenone was found to be a suitable substrate, and high enantioselectivities were obtained (Table 4, entries 3 and 4). In the cases of p-ketoesters, 2-oxocyclopentanecarboxylates are suitable for this reaction, and good yields and good enantioselectivities were observed (Table 5, entries 2, 7, and 8). 

They also investigated asymmetric epoxidation reactions using the BINOL-calcium catalyst. Under optimum reaction conditions, a,p-unsaturated enones were oxidized using BuOOH in moderate to good enantioselectivities [43, 45]. This is the first example of a Ca-catalyzed asymmetric epoxidation (Scheme 3). 

Table 15 Catalytic 1,4-addition reaction and asymmetric protonation sequence using a chiral Pybox-calcium catalyst...

Antilla et al. also investigated chiral calcium BINOL phosphate catalysts [94] for reviews of asymmetric phospination reactitMis, see [95, 96]. This type of calcium catalyst was apphed to asymmetric phosphinatimi reactions (Table 24). Not only a chiral magnesium phosphate but also a chiral calcium phosphate was... 

Kobayashi et al. have also applied their chiral coordinative calcium catalysts successfully to asymmetric addition of malonates to imines, and the desired products were obtained in high yields with moderate to good enantioselectivities (Table 25) [97]. Several aromatic IV-Boc-imines bearing electron-withdrawing or donating groups were surveyed, and the enantioselectivities were around 70 % ees (entries 1-13). Unfortunately, an alkyl-substituted imine did not work well (entry 14). 

Crameri et al. (1997) have reported an asymmetric hydrogenation constituting an important step in the production of a new calcium antagonist, Mibefradil (POSICOR) (of Hoffmann-LaRoche). Pilot-scale synthesis of (S)-2-(4-flurophenyl)-3-methylbutanoic acid by the asymmetric hydrogenation of 2-(4-fluorophenyl)-3-methyl but-2-enoic acid with a [Ru (/ )-MeOBIPHEP)(OAc)2]-catalyst has been described. The hydrogenation was performed in a continuous mode in a cascade stirred-tank reactor system at a pressure of 270 bar. A large reduction in total reactor volume compared to the batch mode was realized. 

L-Tartaric acid is an abundant constituent of many fruits such as grapes and bananas and exhibits a slightly astringent and refreshing sour taste. It is one of the main acids found in wine. It is added to other foods to give a sour taste and is normally used with other acids such as citric acid and malic acid as an additive in soft drinks, candies, and so on. It is produced by acid hydrolysis of calcium tartrate, which is prepared from potassium tartrate obtained as a by-product during wine production. Optically active tartaric acid is used for the chiral resolution of amines and also as an asymmetric catalyst. 

Asymmetric Epoxidation of Electron-deficient trans-Olefins. (f )-l can also catalyze epoxidation of electron-deficient trans -olefins, especially ( )-cinnamate derivatives (eq 4). With 5 mol % of (f )-l, epoxidation of acrylate (5) is completed in 27 h with 74% yield and 85% ee. The crude product can be purified using a continuous dissolution and crystallization process to afford enantiomerically pure product and recover the ketone catalyst simultaneously. A similar practical method has been employed for large-scale synthesis of a key intermediate for diltiazem hydrochloride (a potent calcium antagonist for treatment of cardiovascular disease). 

Thiourea 123 while bearing only one chiral carbon atom is an adequate catalyst. Although much less commonly employed in the present context for calcium salts, one such appears to he able to team up with ent-96K to direct asymmetric Michael reaction involving a glycine derivative. ... 

Kinetic resolution of secondary allylic alcohols by Sharpless asymmetric epoxidation using fert-butylhydroperoxide in the presence of a chiral titanium-tartrate catalyst has been widely used in the synthesis of chiral natural products. As an extension of this synthetic procedure, the kinetic resolution of a-(2-furfuryl)alkylamides with a modified Sharpless reagent has been used . Thus treatment of racemic A-p-toluenesulphonyl-a-(2-furfuryl)ethylamine [( )-74] with fert-butylhydroperoxide, titanium isopropoxide [Ti(OPr-/)4], calcium hydride (CaHa), silica gel and L-(+)-diisopropyl tartrate [l-(+)-DIPT] gave (S)-Al-p-toluenesulphonyl-a-(2-furfuryl)ethylamine [(S)-74] in high chemical yield and enantiomeric excess . Similarly prepared were the (S)-Al-p-toluenesulphonyl-a-(2-furfuryl)-n-propylamine and other homologues of (S)-74 using l-(+)-D1PT. When D-(—)-DIPT was used, the enantiomers were formed . ... 

Cis and trans crotonamides can also polymerize by hydrogen transfer polymerization. Sodium r-butoxide in pyridine yields identical polymers from both isomers. Also, hydrogen transfer polymerization of acrylamide with optically active, basic catalysts yields optically active polymers. The reactions can be carried out in toluene, using optically active alcotxolates of amyl alcohol. The initiating ability of the metal ions is in the following order, Na > Ba > Ca > Mg > Al. Optically active polymethacrylamide forms with optically active barium and calcium alcoholates, but not with the other cations.In this reaction, however, the asymmetric synthesis takes place... 

Kumaraswamy et al. prepared a calcium-BINOL catalyst 132 and applied it in asymmetric Michael and epoxidation reactions. At the outset of their study, they found the choice of calcium salt was important for the enan-tioselectivity. After optimisation, they prepared 132 by the reaction of calcium chloride with potassium-BINOL. Using this catalyst, moderate yields and enantioselectivities were obtained for the Michael addition of malonates 4 or p-ketoesters 101 to enones 10, giving products 136 and 137. The same authors extended this work to the epoxidation of enones using tert-butyl hydroperoxide 102 again with moderate results (Scheme 3.42). 

Kobayashi et al. developed catalytic asymmetric 1,4-additions using chiral calcium species prepared from calcium isopropoxide and chiral bisoxazoline ligands 39, 166 and 168. They found that calcium pyBOX catalysts could effectively mediate catalytic asymmetric additions of 1,3-dicarbonyl compounds 4 to nitroalkenes 86, N-Boc-imines 138 or unsaturated amides 49 giving products 165,167 and 170, respectively. Neutral coordinative ligands worked well in these reactions, giving a noticeably faster rate of reaction... 

Commercial development of calcium polyphosphate fibres Discovery of new class of aluminophosphate molecular sieves Preparation of first carbophosphene - (bis methylene phosphorane) Discovery of Phospha-Cope rearrangement Synthesis of first compound with an As=P bond Cyclo-P, triple decker compound made First asymmetric hydrogenation catalyst discovered (a metallophosphine complex)... 

Surprisingly, there was only one example of asymmetric calcium-catalyzed aldol reaction so far. In 2001, Noyori and Shibasaki (149) developed a chiral hy-drobenzoin/Ca complex for an asymmetric cataljdic direct aldol reaction of acetophenone and aliphatic aldehydes, in which the Ca catalyst system prepared from Ca[N Si(CH3)3 2](thf)2, (S,S)-hydrobenzoin 106, and KSCN (1 3 1 mol... 

---