Dihydroquinines, and

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. 

The 1,2-diol is liberated easily from cyclic osmate ester by either reductive or oxidative hydrolysis.213 Importantly, the ligand acceleration has been utilized extensively for the production of chiral 1,2-diols from (achiral) olefins using optically active amine bases (such as L = dihydroquinidine, dihydroquinine and various chiral diamine ligands).215... 

The first attempt to effect the asymmetric cw-dihydroxylation of olefins with osmium tetroxide was reported in 1980 by Hentges and Sharpless.54 Taking into consideration that the rate of osmium(VI) ester formation can be accelerated by nucleophilic ligands such as pyridine, Hentges and Sharpless used 1-2-(2-menthyl)-pyridine as a chiral ligand. However, the diols obtained in this way were of low enantiomeric excess (3-18% ee only). The low ee was attributed to the instability of the osmium tetroxide chiral pyridine complexes. As a result, the naturally occurring cinchona alkaloids quinine and quinidine were derived to dihydroquinine and dihydroquinidine acetate and were selected as chiral... 

Osmium tetroxide hydroxylations can be highly enantioselective in the presence of chiral ligands. The most highly developed ligands are derived from the cinchona alkaloids dihydroquinine and dihydroquinidine.40 The most effective ligands are dimeric derivatives... 

Figure 6.40 (Thio)urea catalysts derived from dihydroquinine and dihydroquinidine screening results obtained from the asymmetric Michael addition of dimethyl malonate to frans-p-nitrostyrene.

Dihydroquinine and dihydroquinidine are not enantiomeric (although the green centres are inverted in dihydroquinidine, the black ones remains the same), but they act on the dihydroxylation as though they were—here, after all that introduction, is a real example, and probably the most remarkable of any in this chapter. 

While quinine in dilute sulfuric add immediately reduces a one per cent solution of potassium permanganate, the permanganate color persists for some moments in a similar solution of pure dihydroquinine, and this test should be performed as a control of the purity of the product obtained. 

Preparative Methods the acetate is prepared from dihydroquinine and the p-chlorobenzoate is commercially available. The phthalazine-derived bis(dihydroquinine) ligand is commercially available. A formulation of the standard reactants for the asymmetric dihydroxylation (AD-mix-a) on the small scale has been developed and is commercially available. AD-mix-a (1 kg) consists of potassium osmate (0.52 g), the phthalazine-derived ligand (5.52 g), K3pe(CN)6 (700 g), and powdered K2CO3 (294 g). 

Very recently, using structurally varied PTCs based on quinine, quinidine, dihydroquinine, and dihydroquinidine, Berkessel and coworkers conducted the asymmetric epoxidation of 2-methylnaphthoquinone (precursor of vitamin K3) with an aqueous solution of NaOCl at —10 °C in chlorobenzene [18], Among these new catalysts, the phase-transfer catalyst 13 bearing an extra chiral moiety at the quinudidine nitrogen atom provided an enantioseledivity of 79% ee with good yield (86%). However, it was found that the best results were achieved with the readily... 

In 2008, Jorgensen and coworkers reported the first example of the asymmetric conjugate addition of (5-ketoesters 184 to the vinyl bisphosphonate esters 183 catalyzed by the parent cinchona alkaloids (20 mol%) such as dihydroquinine and dihydroqui-nidine [57]. High yields and enantioselectivities (up to 99% ee) were achieved for a wide range of indanone-based (3-ketoesters as well as various 5-tert-butyloxycarbonyl... 

Enantioselective syn dihydroxylation (also aminohydroxylation)8 of olefins using AD-mix-a and AD-mix-p from phthalazine-dihydroquinidine or phthalazine- dihydroquinine and 0s04 or by a new ligand (DHQ)2 PYR or (DHQD)PYR respectively (see 1st edition). 

NMR Spectra. Uskokovid was probably the first to report the difference in the H-NMR spectra of an optically pure compound and its racemate (55). As illustrated in Scheme 32, the spectra of optically pure dihydroquinine and the racemate differ significantly when taken at the same concentration in chloroform-d. The spectrum of the partially resolved compound affords two sets of peaks whose areas are proportional to the relative amount of each enantiomer. These observations can be understood by considering the presence of the solute-solute interactions of the enantiomers. Thus, to the extent that there is some solute aggregation, enantiomers may exhibit different spectra. 

Asymmetric catalytic osmylation (14, 237-239 15, 240-241 16, 249). In the early versions of this reaction the asymmetry was obtained by use of esters of dihydroquinine and dihydroquinidine as ligands. Markedly higher enantioselectivity obtains by use of ligands 1 and 2, prepared by reaction of 1,4-dichlorophthalazine with dihydroquinidine (ligand 1) and dihydroquinine (ligand 2). ... 

B. 2HBr, 2H2O, in leaf-like masses of prisms, m.p. 180-90°, and the nitrate, B. HNO3, flattened needles, m.p. 220-2°. On methylation the base yields dihydroquinine and a series of homologues of hydro-quinine has been prepared from it, e.g., (1) ethylhydrocupreine hydrochloride, B. HCl, rhombic crystals, m.p. 252-4°, —123-6° (HjO) the... 

In the alkylhydrocupreines and alkylhydrocupreidines, R becomes OAlk, and R becomes. CHj. CH3 (homologues of dihydroquinine and dihydroquinidine). 

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