Sharpless dihydroxylation,

A stepwise mechanism involving osmaoxetane seems to be more consistent with the experimental data than the corresponding concerted [3 + 2] mechanism  

The catalytic cycle is shown on the next page (page 337, the secondary cycle is shut off by maintaining a low concentration of olefin)  

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

Another important reaction associated with the name of Sharpless is the so-called Sharpless dihydroxylation i.e. the asymmetric dihydroxylation of alkenes upon treatment with osmium tetroxide in the presence of a cinchona alkaloid, such as dihydroquinine, dihydroquinidine or derivatives thereof, as the chiral ligand. This reaction is of wide applicability for the enantioselective dihydroxylation of alkenes, since it does not require additional functional groups in the substrate molecule ... 

With this reaction, two new asymmetric centers can be generated in one step from an achiral precursor in moderate to good enantiomeric purity by using a chiral catalyst for oxidation. The Sharpless dihydroxylation has been developed from the earlier y -dihydroxylation of alkenes with osmium tetroxide, which usually led to a racemic mixture. 

By using the Sharpless dihydroxylation, a variety of compounds have been transformed to diols with high enantiomeric excesses. The asymmetric dihydroxylation has a wide range of synthetic applications. As an illustration, the dihydroxylation was used as the key step in the synthesis of squalestatin 1 (3.8) (Scheme 3.2).74... 

Scheme 55 Electrochemical enantioselective Sharpless dihydroxylation of alkenes.

Similar MeO-PEG-bound DHQD ligand systems were generated by Bokn [86] and Zhang [87] and also showed very good activity and selectivity under Sharpless dihydroxylation conditions. 

More recently, in light of the development of the Sharpless asymmetric dihydroxylation protocol [20], we have approached the synthesis of diols such as 14 (Scheme 2) from the alkene. Thus, treatment of the alkenyl D-glucosides 15 vmder the conditions of the Sharpless dihydroxylation gave a range of diols 16 with varying diastereoisomeric excesses (Table 1). One of these mixtures of diols, upon recrystallization, yielded the pure diastereoisomer, namely the diol 14. This procedure now gives a very rapid and efficient entry into one of the precursor diols for the synthesis of the optically-pure epoxides [21]. 

Stilbene diols such as 3 are gaining prominence both as synthetic intermediates and as effective chiral auxiliaries. While the diols can be prepared in high by Sharpless dihydroxylation, it would be even more practical to prepare them by direct asymmetric pinacol coupling. N. N. Joshi of the National Chemical Laboratory in Pune reports (J. Org. Chem. 68 5668,2003) that 10 mol % of the inexpensive Ti salen complex 2 is sufficient to effect highly enantioselective and diastereoselective pinacol coupling of a variety of aromatic aldehydes. Most of the product diols are brought to >99% by a single recrystallization. 

The catalytic cycle in the asymmetric Sharpless dihydroxylation is Discussion... 

Sharpless dihydroxylation takes place under basic conditions, so another reaction occurs after formation of the two diols in situ. 

Sharpless dihydroxylation Os ethyl cinnamate Woltinger, 2001b... 

J. Woltinger, H. Henniges, H.-P. Krimmer, A. S. Bommarius, and K. Drauz, Application of the continuous Sharpless dihydroxylation, Tetrahedron Asymm. 

The use of chiral amines enables enantioselective conversions, such as (DHQ)2-PHAL and (DHQD)2-PHAL in the Sharpless Dihydroxylation. 

Corey used the Sharpless dihydroxylation protocol. Which reagents are necessary ... 

In a comparison study for the synthesis of the arrhythmia and hypertension drug candidate 7, the intermediate epoxide 8 was prepared by a Sharpless dihydroxylation and a Jacobsen HKR. The latter HKR method gave the highest ee s.116... 

The Sharpless dihydroxylation method has been run at scale by Pharmacia-Upjohn with o-isopropoxy-m-methoxysytrene as substrate and /V-mcthylmorpholine /V-oxide as oxidant.160... 

A variation on the Sharpless dihydroxylation methodology allows for the preparation of amino alcohols. As the groups are introduced in a syn manner, this complements an epoxide opening or a similar reaction that uses substitution at one center (Chapter 22). Higher selectivity is observed when one of the alkene substituents is electron withdrawing, as in an ester group (Scheme 9.32).179-181... 

Different polyethylene glycol polymers were used in various papers and proved to be very reliable and useful for different classes of molecules their use for the synthesis of peptides [180, 181], of peptidomimetics [182] and of oligosaccharide libraries [183] was reported as the development and the use of a new PEG-linked traceless linker [184, 185], the selection of ligands for asymmetric Sharpless dihydroxylation [186-188], the use of PEG-linked triarylphosphines for LPCS requiring Mitsunobu or Staudinger conditions [189], the use of PEG-based supports to prepare a library of [l,4]oxazepine-7-ones [190] and the use of PEG-supported Schiff bases for the synthesis of a-substituted amino acids [191], Other examples of soluble polymers used for LPCS may include cellulose[192], polyacrylamide [193] polyvinyl alcohol [194, 195], various copolymers [196, 197] and NCPS [198-200]. Three excellent reviews [201-203] summarized the properties of PEG and other soluble polymers and their applications to the synthesis of peptides, oligonucleotides,... 

An orf/io-directed lithiation allows the conversion of 25 to aryl iodide 40. Reductive ether formation of aldehyde 40 with crotyl alcohol yields compound 41. Intramolecular Heck reaction of 41 affords a mixture of the olefins 42 and 43. The undesired alkene 42 can be isomer-ized quantitatively to the desired enol ether 43 with Wilkinson s catalyst. Sharpless dihydroxylation ee 94 %) of the enol ether 43 provides lactol 44, which is oxidized directly to lactone 45. Finally, the pyridone-O-methyl ester is cleaved under acid conditions (45 — 7). 

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