Dihydroquinidine acetate

Schollkopf, U. Westphalen, K.-O. Schroder, J. Horn, K. Justus Liebigs Ann. Chem./Liebigs Ann. Chem. 1988,781. 

Solubility p-ClC6H4C(0)- sol CH2CI2, EtjO, EtOH, EtOAc. 

Form Supplied in the p-chlorobenzoate is available as a white foam. 

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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... 

In Figure 14.14 we have depicted the most striking result from the 1980 paper involving /rara-stilbenc as the substrate and dihydroquinine acetate. After addition the osmate ester was decomposed by reduction with UAIH4, a common procedure in the early days, to give the threo-dio. A diastereomer of the ligand, dihydroquinidine acetate, gave similar e.e. but the opposite enantiomer. The enantioselectivity was 83%. 

Optically active ds.vic-diofa.1 It is known that pyridine catalyzes the hydroxyl-ation of alkenes with Os04 and that the osmate ester intermediates form an isolable complex with pyridine (1, 760-761). Hentges and Sharpless reasoned that a similar chiral amine could induce chirality in the diol. And indeed addition of 1 equivalent of 1 or of the C8-diastereoisomer, dihydroquinidine acetate (2), does result in vic-diols in fair to high enantiomeric excess, particularly in reactions performed in toluene at —78°. Opposite stereoselectivities are exhibited by 1 and 2. Optical yields range from 25 to 85%. Use of an amine in which the chiral center is two carbon atoms removed from the coordination site lowers the optical yield to 3 18%. 

Protected a,p-dihydroxy aldehydes have been prepared by oxidation of acetals of a,p-unsaturated aldehydes with osmium tetroxide in the presence of (23), and a remarkable level of enantioselection (ee 90%) thereby achieved. Oxidation of chiral acetals of a, -unsaturated aldehydes in which chirality resides in the noncarbonyl moiety with osmium tetroxide-dihydroquinine acetate (or dihydroquinidine acetate) may be regarded as a process in which double stereoselection is at work and a high dia-stereoisomeric ratio of products may be obtained. 

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

For additional examples of regioselective asymmetric dihydroxy lations, see Dihydroquinidine Acetate. 

For additional examples and an extensive discussion on the use of these ligands in asymmetric dihydroxylation reactions, see Dihydroquinidine Acetate. 

Dihydropyranes, 236, 258 Dihydroquercetin, 351, 352 Dihydroquinidine acetate, 291 Dihydro tetrakis(tri-n-bu tylphosphine)-ruthenium(II), 148... 

When the reaction of 3-methylindole is done in a 1 1 mixture of methanol and the ionic solvent [bmim BF4 ] an essentially quantitative yield of the 3-fluorooxindole is obtained [41]. Combining Selectfluor with dihydroquinidine acetate leads to fluori-nation of oxindoles in up to 80% ee. The reaction is believed to proceed by transfer fluorination in which the iV-fluoro alkaloid is the immediate fluorinating agent [42]. 

Shibata et al. [2,6] further extended this Cinchona alkaloid-mediated asymmetric transfer fluorination reaction to substrates with activated methylene groups, including acyclic (3-cyanoesters, cyclic (3-ketoesters, and oxindole substrates. Representative products, along with the optimal Cinchona alkaloids for these reactions, are shown in Scheme 13.3. Reaction conditions for the acyclic (3-cyanoesters and the cyclic (3-ketoesters used both (a) Selectfluor as the achiral electrophilic fluorine source in MeCN/CHaCla (3 4) at — 80 C and (b) dihydroquinidine acetate (DHQDA) in stoichiometric quantities. The oxindole substrates required the use of stoichiometric bis-Cinchona alkaloids, (DHQlaAQN or (DHQDlaPYR, to obtain useful yields and selectivities. Reactions of these substrates were run in MeCN at 0°C and also employed Selectfluor as the achiral electrophilic fluorine source. 

Improved procedures for osmium-catalysed vicinal oxyamination of olefins by JV-chlorosodiocarbamates-Hg(N03)2-Et4NOAc are recommended especially for trisubstituted systems. Asymmetric induction in the reaction of OSO4 with olefins using dihydroquinidine acetate in up to 83% e.e. is now possible. "... 

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