Sharpless asymmetric dihydroxylation Regioselectivity

Aminohydroxylation of unsymmetrically substituted alkenes, in contrast to dihydroxylation, may give two possible regioisomers of aminoalcohol derivatives but asymmetric aminohydroxylation, by using the same catalytic system as that used for Sharpless asymmetric dihydroxylation, can be highly regioselective as well as enantioselective. 

SCHEME 13.49 Sharpless asymmetric dihydroxylation of an allylic silyl ether configuration inversion via regioselective intramolecular displacement of cyclic sulfates. 

Asymmetric dihydroxylation of trifluoromethylalkenes is also useful for construction of enantio-enriched trifluoromethylated diols usable for trifluoromethylated amino acids with chiral hydroxyl group. Thus, Sharpless AD reaction of 16 provides diol 17 with excellent enantioselectivity. Regioselective and stereospecific replacement of the sulfonate moiety in 18 with azide ion enables the introduction of nitrogen functionality. A series of well-known chemical transformation of 19 leads to 4,4,4-trifluorothreonine 20 (see Scheme 9.6) [16]. Dehydroxylative-hydrogenation of 21 by radical reaction via thiocarbonate and subsequent chemical transformation synthesize enantio-enriched (S)-2-amino-4,4,4-trifluoro-butanoic acid 22 [16]. Both enantiomers of 20 and 22 were prepared in a similar manner from (2R,3S)-diol of 17. 

The key step of a recent synthesis of fosfomycin is the Sharpless asymmetric di hydroxylation (AD) reaction.Dibenzyl ( )-l-propenylphosphonate is prepared in 94% yield from ( )-propenyl bromide and dibenzyl phosphite in THF at 60°C in the presence of I il.,N and catalytic amount of PdfPPh,). A modified AD-mix-a is used to speed up the dihydroxylation reaction. The resulting 5y/r-a,3-dihydroxyphosphonate is isolated in 65% yield after recrystallization and then submitted to regioselective oc-sulfonylation followed by cyclization by treatment with K CO, in acetone at room temperature to produce di benzyl (17 ,25)-l,2-epoxypropylphosphonate in 67% yield (Scheme 4.31). = Fosfomycin can be obtained by hydrogenolysis of this epoxyphosphonate. i... 

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