Olefin dihydroxylation dihydroquinine

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 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. 

Recently, effective chiral ligands for the enantioselective dihydroxylation of olefins have been intensively investigated. Among the reported asymmetric dihydroxylation systems, the superiority of an H20/f-Bu0H-K3Fe(CN)6/K2C03 system with chiral ligands, that is, dihydroquinidine (DHQD) and/or a dihydroquinine (DHQ) derivative, has been mentioned (see Sect. 15.2.4.7) [476]. 

Ligand variation has resulted in considerable improvement of the reaction s efficiency (Scheme 38). With 9-0-(9 -phenanthryl) (PHN) ethers and 9-0-(4 -methyl-2 -quinolyl) (MEQ) ethers of dihydroquini-dine and dihydroquinine as ligands, olefins of various substitution patterns, mono-, gem-di-, trans-di-, and certain trisubstituted substrates can be dihydroxylated with high enantioselectivity (89). Some examples of these reactions are given in Scheme 38. The reaction occurs at either ambient or ice-bath temperature with the solid, nonvolatile Os(IV) salt, K20s02(0H)4, instead of 0s04. The substrate/catalyst ratio for this reaction is 2000 for terminal olefins. 

In order to predict facial selectivity, Sharpless and co-workers invoke a mnemonic device.25 To an approaching olefin, the greatest steric constraints are presented by the NW, and to an even greater extent, the SE quadrants. The SW and NE quadrants are more open and, in addition, the SW quadrant contains what is described as an attractive area . The attractive area is particularly well suited to accommodate flat aromatic groups. The olefin positions itself according to the constraints imposed by the ligand and is dihydroxylated from above (p-facc), in the case of dihydroquinidine derivative, or from below (a-face) in the case of dihydroquinine derivatives. The commercially available AD-mix-a and AD-mix-P are chosen according to this mnemonic. 

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). 

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