Dihydroquinidine 4-chlorobenzoate

Catalytic asymmetric dihydroxylation (14, 237-239 15, 240-241). Complete details are now available for this reaction with a solid substrate, ftms-stilbene, in acetone/water (3 1, v/v) with dihydroquinidine 4-chlorobenzoate as catalyst.1 4... 

Dihydroquinidine 9-0-(9 -phenanthryl) ether4 (Aldrich, Cat. No. 38195-0 Hydroquinidine 9-phenanthryl ether) gave the highest enantioselectivity compared with several other commercially available dihydroquinidine derivatives 34% ee with dihydroquinidine 4-chlorobenzoate (Aldrich, Cat. No. 33648-3 Hydroquinidine 4-chlorobenzoate) and 61% ee with dihydroquinidine-9-0-(4 -methyl-2 -quinolyl) ether (Aldrich, Cat. No. 38194-2 Hydroquinidine 4-methyl-2-quinolyl ether). The submitters report that the reaction can be run on 0.5-mol scale using this procedure to afford comparable yields and enantiomeric purity of the diol product. 

X-ray crystallographic structures of the cw-dioxo osmium(VI) esters derived from dihy-droquinine-4-chlorobcnzoate/Os04/( )-2,2,5,5-tetramethyl-3-hexene and dihydroquinidine 4-chlorobenzoate/Os04/(i )-2,5-dimethyl-3-hexene have also been reported 22. Inspection of these sixteen-electron complexes reveals that, despite the considerable distance between the ligand stereocenters and the reacting site, the 4-chlorobenzoyl moieties effectively shield one of the two possible modes of alkene approach. 

By combining OSO4 and a natural alkaloid, asymmetric oxidation has been developed. Oxidation of /mn -stilbene dissolved in aqueous acetone with morpholine-7V-oxide, dihydroquinidine 4-chlorobenzoate as the ligand, and 0.4 mol % of OSO4 as... 

DIHYDROPYRIDINE EQUIVALENT, 70, 54 Dihydroquinidine, benzoate ester, 70, 49 DIhydroquinIdIne 4-chlorobenzoate, 70, 47 Dihydroquinidine, 2-naphthoate ester, 70, 49 Dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate, 70, 80 Dilsobutylaluminum hydride, 70, 20... 

Dihydroquinidine 4-chlorobenzoate Is available from the Aldrich Chemical Company, Inc. The optical rotation of the commercial sample employed by the checkers had an [a] of-ea-g (EtOH, cO.95). 

Methylmorpholine N-oxide Morpholine, 4-methyl-, 4-oxide (8,9) 7529-22-8) Dihydroquinidine 4-chlorobenzoate Cinchonan-9-ol, lO,l1-dihydro-6 -methoxy-,... 

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. 

After the "asymmetric epoxidation" of allylic alcohols at the very beginning of the 80 s, at the end of the same decade (1988) Sharpless again surprised the chemical community with a new procedure for the "asymmetric dihydroxylation" of alkenes [30]. The procedure involves the dihydroxylation of simple alkenes with N-methylmorpholine A -oxide and catalytic amounts of osmium tetroxide in acetone-water as solvent at 0 to 4 °C, in the presence of either dihydroquinine or dihydroquinidine p-chlorobenzoate (DHQ-pClBz or DHQD-pClBz) as the chiral ligands (Scheme 10.3). 

This procedure has been modified to become an effective catalytic procedure in which iV-methyl-moipholine A -oxide is used as the secondary oxidant. In this manner, ( )-stilbene has been converted into (+)-r/irco-hydrobenzoin (55% yield after two reciystallizations, >99% ee) on a one molar scale, by treatment with osmium tetroxide (0.002 mol equiv.) and iV-methylmoipholine 1 -oxide (1.2 mol equiv.) in aqueous acetone in the presence of dihydroquinidine p-chlorobenzoate (0.134 mol equiv.). The latter compound can be recovered in 91% yield. 

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). 

Purification dihydroquinine / -chlorobenzoate is recovered after a dihydroxylation reaction using the same method as that described for Dihydroquinidine Acetate. 

Sharpless asymmetric dihydroxylation procedure was applied to the synthesis of the side chain of azinomycin A (equation Horner-Emmons condensation of phospho-nate 36 with a -aziridine substituted acrolein afforded dehydroamino acid diene 37. Treatment of the diene with catalytic amounts of an osmium reagent and dihydroquinidine (DHQD) p-chlorobenzoate resulted in asymmetric dihydroxylation, producing diol 38. Diol 38 was further converted to the naphthyl ester. 

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