Asymmetric catalytic osmylation

Asymmetric catalytic osmylation.s Chiral cinchona bases are known to effect asymmetric dihydroxylation with 0s04 as a stoichiometric reagent (10, 291). Significant but opposite stereoselectivity is shown by esters of dihydroquinine (1) and of dihydroquinidine (2), even though these bases are diastereomers rather than enantiomers. 

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 dihydroqui-ninc and dihydroquinidine as ligands. Markedly higher enantiosclcctivity obtains by use of ligands 1 and 2, prepared by reaction of 1,4-dichlorophthalazinc with dihydroquinidine (ligand 1) and dihydroquininc (ligand 2). ... 

Enantioselective total syntheses of (-)-6-epitrehazolin and (+)-trehazolin were achieved by the synthesis of 275, which began with an asymmetric heterocycloaddition between [(benzyloxy)methyl]cyclopentadiene (263),108 prepared from thallous cyclopentadienide, and the acylnitroso compound arising from in situ oxidation of (,S )-mandelohydroxamic acid (264) with tetrabutylammonium periodate. Cycloaddition led to a mixture of 265 and its diastereomer (Scheme 35).109 The inseparable mixture was reduced to afford cyclopentenes 266 and 268 in 40% and 11 % overall yields, respectively, from thallous cyclopentadienide. Catalytic osmylation of 266 favored syn addition, while the osmylation of diacetate 267 was more selective and nearly quantitative, affording, after acetylation, compounds 270 and 269 in >5 1 ratio. 

A full account has been given of the work by Brimacombe s group (see Vol. 23, p. 9) on the formation of octuronic acid derivatives by catalytic osmylation of a,p-unsaturated esters in the presence of Sharpless chiral ligands, where double asymmetric induction can be used to enhance the Kishi selectivity.66 The trehalose derivative (44) could be homologated to the bis-uronic acid (45) using a carbonyl insertion procedure (Scheme 13), as well as by use of the reaction of cyanide ion on the ditriflate analogous to (44)67... 

The interest in asymmetric synthesis that began at the end of the 1970s did not ignore the dihydroxylation reaction. The stoichiometric osmylation had always been more reliable than the catalytic version, and it was clear that this should be the appropriate starting point. Criegee had shown that amines, pyridine in particular, accelerated the rate of the stoichiometric dihydroxylation, so it was understandable that the first attempt at nonenzymatic asymmetric dihydroxylation was to utilize a chiral, enantiomerically pure pyridine and determine if this induced asymmetry in the diol. This principle was verified by Sharpless (Scheme 7).20 The pyridine 25, derived from menthol, induced ee s of 3-18% in the dihydroxylation of /rcms-stilbene (23). Nonetheless, the ee s were too low and clearly had to be improved. 

The history of asymmetric dihydroxylation51 dates back 1912 when Hoffmann showed, for the first time, that osmium tetroxide could be used catalytically in the presence of a secondary oxygen donor such as sodium or potassium chlorate for the cA-dihydroxylation of olefins.52 About 30 years later, Criegee et al.53 discovered a dramatic rate enhancement in the osmylation of alkene induced by tertiary amines, and this finding paved the way for asymmetric dihydroxylation of olefins. 

Pentitol synthesis An asymmetric synthesis of L-arabinitol involves condensation of the (E)-a,fJ-unsaturated ester (2) with the anion of methyl (R)-p-tolyl sulfoxide (1). The resulting p-keto sulfoxide (3) is reduced stereoselectively by ZnCl2/DIBAH (13, 115-116) to 4. Osmylation of 4 with (CH,)3NO and a catalytic amount of 0s04 (13, 224-225) yields essentially a single triol (5). Finally, a Pum-merer rearrangement of the sulfoxide followed by reduction of an intermediate... 

The Sharpless epoxidation (eq. 5)23 may be performed both stoichiometrically and catalytically with high asymmetric induction, whereas the complementary osmylation (eq. 6)24 is performed in the catalytic version. 

---