Dihydroquinidines, and

Hydrocupreidine (Dihydrocupreidine), C19H24O2N2. a H20. This base, isomeric with the foregoing, is made by demethylating dihydroquinidine, and was first definitely obtained by Heidelberger and Jacobs. It forms glistening, cream-tinted, hexagonal plates, m.p. 195° (dec.), -(- 227-2°... 

Using the (— )-Aowocincholoipon produced as described, Rabe and Schultze, by the same sequence of reactions, have produced (—)-dihydro-quininone (m.p. 98-9[a]f, ° — 70-0° (final value EtOH)), which on hydrogenation in presence of palladium gave a mixture of bases, of which (—)-dihydroquinidine and (-j-)-dihydroquinine were isolated. The characters of these mirror-image isomerides of dihydroquinidine and dihydroquinine respectively have been given already with the directions of rotation at the centres of asymmetry C , C , C , C (see table, p. 446). 

In summary, the reaction of osmium tetroxide with alkenes is a reliable and selective transformation. Chiral diamines and cinchona alkakoid are most frequently used as chiral auxiliaries. Complexes derived from osmium tetroxide with diamines do not undergo catalytic turnover, whereas dihydroquinidine and dihydroquinine derivatives have been found to be very effective catalysts for the oxidation of a variety of alkenes. OsC>4 can be used catalytically in the presence of a secondary oxygen donor (e.g., H202, TBHP, A -methylmorpholine-/V-oxide, sodium periodate, 02, sodium hypochlorite, potassium ferricyanide). Furthermore, a remarkable rate enhancement occurs with the addition of a nucleophilic ligand such as pyridine or a tertiary amine. Table 4-11 lists the preferred chiral ligands for the dihydroxylation of a variety of olefins.61 Table 4-12 lists the recommended ligands for each class of olefins. 

Fig. 9. Biotransformation of dihydroquinidine (and acylated derivatives) to the corresponding (3S)-3-hydroxy compounds (as % observed at the reaction plateau), using various collection strains of Mucor plumbeus (ATCC American Type Culture Collection CBS Centraalbureau voor Schimmelcultures DSM Deutsche Sammlung von Mikroorganismen MMP Mycotheque of the Paris Museum of National History)...

With this aim, the group of Norrby developed a transition state force field for the study of the asymmetric dihydroxylation reaction [91]. This force field is purely developed from quantum mechanical reference data [92]. In their studies they use different ligands from the first generation (where the amine ligands are the alkaloids dihydroquine or dihydroquinidine) and second generation (where a symmetric linker couples two alkaloid units), and several alkenes. The calculated ee s are in very good agreement with experiment. 

Preparative Methods the acetate is prepared from dihydroquinidine and the p-chlorobenzoate is commercially available. The phthalazine-derived bis(dihydroquinidine) ligand is commercially available. A formulation of the standard reactants for the asymmetric dihydroxylation (AD-mix-p) on the small scale has been developed and is commercially available. AD-mix-p (1 kg) consists of potassium osmate (0.52 g), the phthalazine-derived ligand (5.52 g), K3Fe(CN)6 (700 g), and powdered K2CO3 (294 g). 

However, the use of these dihydroquinidine and dihydroquinine phthalazine ligands does not improve the enantiosclcctivity of c/.v-disubstituted alkencs.2 The problem in this case can be solved by use of carbamate ligands such as (9-0-indolinylcarbamoyl)dihydroquinidine, DHQO-IND (I). 

Asymmetric dihydroxylation of the side-chain of Z-1-(4-meth-oxyphenyl)-1-(tert-butyldimethylsiloxy)-1-propene to give (R)-l-hydroxyethyl 4-methoxyphenyl ketone in 94% yield (99% e.e.) was effected by addition of the alkene to a stirred mixture of osmium tetroxide, potassium ferricyanide, potassium carbonate, a 9-0-(9 -phenanthryl)ether(PHN) of dihydroquinidine and 1 mole of methanesulphonamide in aqueous tert-butanol (1 1), with reaction during 16 hours at ambient temperature. Then treatment with sodium sulphite prior to work-up to gave the product (ref. 130). Other best ligands were the 9-0-(4 -methyl-2 -quinolyl) ethers (MEQ) of dihydroquinine. 

Catalytic hydrogenation of the carbonyl group in the presence of palladium gave dihydroquinine, identical in all respects with the naturally occurring alkaloid. In addition, dihydroquinidine and a stereoisomer, subsequently identified as eptdihydroquinidine (154, 155), were also isolated. Further examination of the reduction mixture revealed the presence of epidihydroquinine, and it was shown that the four isomers are likewise formed in the reduction of dihydroquinidinone with a mixture of aluminum, sodium ethoxide and alcohol. 

The hgands used by the Sharpless group are based on dihydroquinidine (DHQD) (5.01) and dihydroquinine (DHQ) (5.02). Dihydroquinidine and dihydro quinine are diastereomers, although their derivatives behave as pseudo-enantiomers in... 

A diaryIprolinol silyl ether induces ee < 99% for aldehyde a-alkylation on 1,4-addition to acridinium salts. Computational chemistry has been used to explain stereoinduction by a family of iodooxazoline catalysts developed for enantioselective a-tosyloxylation of ketones by m-CPBA/TsOH. a-Benzoyloxylation of ketones (cyclohexanones and 1-indanones) by dibenzoyl peroxide occurs enantioselectively in the presence of a mixture of 9-amino-(9-deoxy)epi-dihydroquinidine and salicylic acid. ° The scope and limitations of asymmetric a-oxyacylation of cyclic ketones by chiral Ai-alkyl-O-acyl hydroxylamines have also been reported. ... 

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