Sharpless dihydroxylation of olefins

Asymmetric Sharpless dihydroxylation of olefins using catalysts supported by polymers with heterocyclic fragments 98EJ021. 

Bolm, C., Gerlach, A. Polymer-supported catalytic asymmetric Sharpless dihydroxylations of olefins. Eur. J. Org. Chem. 1998, 21-27. 

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... 

Excitingly, the electrochemical Os-catalyzed asymmetric dihydroxylation of olefins with Sharpless s ligands yielding the chiral diol (138) via the chiral adduct (137) has been reported [184]. The asymmetric dihydroxylation of olefins (136) is performed by recycling a catalytic amount of potassium ferricyanide [K3Fe(CN)6] in the presence... 

Osmium-catalysed dihydroxylation of olefins is a powerful route towards enantioselective introduction of chiral centers into organic substrates [82]. Its importance is remarkable because of its common use in organic and natural product synthesis, due to its ability to introduce two vicinal functional groups into hydrocarbons with no functional groups [83]. Prof. Sharpless received the 2001 Nobel Prize in chemistry for his development of asymmetric catalytic oxidation reactions of alkenes, including his outstanding achievements in the osmium asymmetric dihydroxylation of olefins. 

Dihydroxylation of olefins followed by oxidation with periodate leads to cyclization and the corresponding carbinolamine. This can then be reduced to the piperidine <2005JOC10182> (Scheme 12). The strategy was used in the synthesis of both the (2A,3i )-3-hydroxypipecolic acid 13 and (2 5, 3A)-3-hydroxypipecolic acid 14 from D-serine. Variations in this strategy toward both trans-isomers of the 3-hydroxypipecolic acid moiety are shown in Schemes 13 and 14. The initial stereochemistry was introduced using Sharpless method <2005JOC360>. 

Recently, electrochemical Os-catalyzed asymmetric dihydroxylation of olefins with Sharpless s ligand has been developed by Amundsen and Balko [450] and by Torii and coworkers [451,452]. 

Ogino, Y., Chen, H., Kwong, H. L., Sharpless, K. B. The timing of hydrolysis-reoxidation in the osmium-catalyzed asymmetric dihydroxylation of olefins using potassium ferricyanide as the reoxidant. Tetrahedron Lett. 1991, 32, 3965-3968. 

This situation obtains for example in the asymmetric vicinal dihydroxylation of olefins (see Fig. 13) reported by Sharpless and coworkers [41]. Coordination of a (chiral) amine to the 0s04 catalyst affords a (chiral) catalyst with much higher activity. 

Ligands have also been attached to polyethylene glycol so that they can be recovered for recycle by the foregoing methods. A phosphine isocyanate has been reacted with polyethylene glycol for use in the Staudinger reaction with alkyl azides to form a phosphine imine.173 An alkaloid has been attached to the monomethyl ether of polyethylene glycol for use in the Sharpless asymmetrical dihydroxylation of olefins. The reaction was complete in the same time, with no decrease in yield or enantioselectivity, as when the alkaloid was used by itself.174 (Asymmetrical reactions are covered in Chap. 10.)... 

The Sharpless group is best known for development of a method for the asymmetrical dihydroxylation of olefins.104 A typical oxidation uses 1 mol% of potassium osmate dihydrate, 1 mol% ligand, potassium carbonate, potassium ferricyanide, and methylsulfonamide in aqueous tert-butyl alcohol. Other oxidants such as A-melhylmor pholine N oxide can be used in place of the potassium ferricyanide. One of the preferred ligands is a bis(dihydro-quinidine ether) of phthalazine (10.46). 

Devise a system for a Sharpless dihydroxylation of an olefin in which no osmium or alkaloid-derived ligand is lost on repeated reuse. You may want to refer to Chaps. 5 and 7 for hints. 

The Sharpless catalytic asymmetric dihydroxylation of olefins, using catalytic amounts of osmium tetroxide in the presence of chinchona alkaloid derivatives, allowed access to a variety of enantiomerically pure 1,2-diols Scheme 3.6.1). 

The discussion about the possible formation of metalla-2-oxetanes in transition metal-mediated oxidation reactions began with the ground breaking work of Sharpless in the field of enantioselective dihydroxylation of olefins with osmium tetraoxide using cinchona alkaloids as ligands [6]. The transfer of the stereochemical information of the chiral ligand to the substrate was explained by Sharpless with a two-step mechanism for the addition reaction, which should occur rather than a concerted [3+2] addition as originally proposed [110] (Fig. 15). 

The first quantum chemical calculations which provided quantitative data about the mechanism of the ds-dihydroxylation of olefins with OSO4 were reported in 1994 by Sharpless etal. [122] andbyVeldkampandFrenking [123]. Previous work by Jorgensen and Hoffmann [ 124] focused on a quahtative orbital analysis using EHT calculations. 

Fig. 20 Reaction mechanism for the two-cycle dihydroxylation of olefins with OSO4 in the presence of chiral ligands L via [3+2] addition suggested by Sharpless...

The first asymmetric synthesis of (20 S)-camptothecin using catalytic asymmetric induction was achieved by Fang et al. in 1994 [74], They carried out a catalytic enantioselective synthesis of Comins s intermediate (23) in order to avoid the use of the expensive chiral auxiliary, 8-phenylmenthol, or similar compound. Intramolecular Heck reaction of pyridine derivative (26) gave the cyclic olefins (27) and (28) in a ratio 1 8. The allylic ether (27) can be isomerized to (28) upon treatment with Wilkinson s catalyst [75], Asymmetric Sharpless dihydroxylation of (28) proceeded successfully when 2,5-diphenyl-4,6-bis(9-0-dihydroquinidyl)pyrimidine [(DHQD)2-PYR] was used as the chiral catalyst [76], and subsequent oxidation gave (29) in 94% ee. Treatment of (29) with acid gave the target molecule (23, Scheme 2.5), which was converted to (20S)-camptothecin in 2 steps using the Comins s procedure [73]. 

Hoi-Lun, K. Sorato, C. Ogino, Y Hou, C. Sharpless, K. B. Preclusion of the "Second Cycle" in the Osmium-catalyzed Asymmetric Dihydroxylation of Olefins Leads to a Superior Process. Tetrahedron Lett. 1990, 31, 2999-3002. 

The osmium-catalyzed vicinal dihydroxylation of olefins with single oxygen donors, typically tert-butyl hydroperoxide or N -methylmorpholine-JV-oxide (NMO), has been known for three decades and forms the basis of the Sharpless asymmetric dihydroxylation of olefins. Recently, Sharpless and coworkers reported that particularly electron-deficient olefins are dihydroxylated more efficiently with NMO (Eq. 2) when the pH of... 

Scheme 14.5 General scheme of the Sharpless AD reaction, Os-mediated dihydroxylation of olefins...

The dihydroxylation of olefins is catalyzed by OSO4. Sharpless has proposed olefin coordination on osminm followed by formation of a metallocycle analogous to met-allacyclobutanes in metathesis, then generation of a 5-membered ring. Another mechanistic possibility is direct formation of the 5-membered ring metallocycle without prior coordination of the olefin on osmium. 

Becker H, Sharpless KB. A new ligand class for the asymmetric dihydroxylation of olefins. Angew. Chem. Int. Ed. Engl. 1996 35 448-451. 

---