Cinchona alkaloid structure induction

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

In the presence of a cinchona alkaloid, certain cyclic carboxylic anhydrides with meso structures are converted to the chiral diacid monoesters in up to 76% ee (Scheme 10) 31). Quinine or cinchonidine and quinidine or cinchonine show opposite asymmetric induction. 

Modifier The effect of the modifier structure is also quite similar to that found for a-ketoesters [7]. Cinchonidine derivatives and quinine lead to an excess of the (R)-hydroxy-acid while the pseudo-enantiomeric cinchona alkaloids (cinchonine and quinidine) give preferentially (S)-product but with much lower enantioselecdvity. Changing the substituent Y at C9 has only an effect on the degree of asymmetric induction but not its direction. OMe and OH are more effective than OAc or H. An interesting exception are the Nj alkylated Cd derivatives which are completely ineffective in the case of the ester. Here, N-methyl-Cd+Cr gives a small excess of the R-enantiomer while N-benzyl-Cd Cl leads an 33% excess of (S)-4-phenyl-2-hydroxybutyric acid ... 

The hydrogenation of trifluoromethylcyclohexyl ketone in toluene or ethanol on Pt-alumina modified by cinchona alkaloids was studied, and depending on the solvents inversion of the enantioselectivity was observed. It was assumed that the structures of intermediates responsible for chiral induction depend mostly on the acidic or non-acidic nature of the hydrogenation medium... 

Fluorinated amino acids and amino alcohols have shown extensive biological activity [18]. In 2008, the Bandini and Umani-Ronchi group developed an efficient Henry reaction between nitromethane and fluoromethyl ketones catalyzed by cinchona alkaloids [19]. They showed that benzoylcupreines bearing electron-withdrawing substituents at the C9 position of the catalyst structure are essential for good results (Table 29.2,14 versus 15). Remarkably, comparable levels of asymmetric induction could be obtained with both aromatic and aliphatic ketones. 

---