CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

Apart from the cinchona alkaloids, few other ligands such as a monodentate 1,4-
diazabicyclo[2.2.2]octane, 44a chiral oxazolidines, 44b etc. have also been used to effect the
transformation with modest 41-73% ees. Some simple chiral diaminocyclohexyl ligands
produced better enantioselection, but a serious drawback results from their bidentate
nature. 45 They form very stable chelates with the osmium (VI) glycolate products which
lead to inhibition of hydrolysis, and as a consequence prevent in situ recycling of the
osmium and the ligand. Thus, all the reactions involving bidentate ligands are
stoichiometric in both OsO 4 and the chiral ligand.
ADH with derivatives of cinchona alkaloids was made catalytic using NMO as the
cooxidant, albeit with less enantioselectivity than the stoichiometric version. 46a A second
catalytic cycle, 46b which exhibited only low or no enantioselectivity accounted for this
discrepancy. Two key discoveries led to a dramatic growth in the ADH reaction. First, the
second catalytic cycle could be eliminated by carrying out the reaction in a biphasic
condition with K 3 Fe(CN) 6 as the stoichiometric cooxidant. 46c Under this condition, OsO 4 is
the only oxidant in the organic phase where the ADH reaction takes place. Hydrolysis of
the osmate ester provides only OsO 4 in the aqueous phase, where it gets reoxidized. Thus,
the combination of K 2 Os 2 (OH) 4 , as a non-volatile osmium source, and the cooxidant,
K 3 Fe(CN) 6 was developed for carrying out the reaction conveniently. The reagent, AD-mix
is now commercially available. Further, the discovery of second generation ligands with
two independent cinchona alkaloid units attached to a heterocyclic spacer, has led to a
considerable increase in both enantioselectivity and scope of the reaction. 46d-f One
representative example of this strategy is the conversion of cinnamyl chloride (42) to the
diol 43. in high ee via the ADH reaction (Scheme II.1.6). 46g
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