Reactions Sharpless asymmetric dihydroxylation

Reactions have been carried out adjacent to the epoxide moiety in order to examine the effects, if any, that the epoxide has on subsequent reactions with respect to the regio- and stereochemical outcome. Dihydroxylation using osmium tetraoxide and Sharpless asymmetric dihydroxylation reactions have been extensively studied using substrates 29 and 31. Initial studies centred on the standard dihydroxylation conditions using AT-methylmorpholine-AT-oxide and catalytic osmium tetraoxide. The diastereomeric ratios were at best 3 2 for 29 and 2 1 for 31, indicating that the epoxide unit had very little influence on the stereochemical outcome of the reaction. This observation was not unexpected, since the epoxide moiety poses minimal steric demands (Scheme 21). 

This is the Sharpless asymmetric dihydroxylation reaction 3 one of the most powerful and versatile catalytic asymmetric reactions ever to be discovered. The Sharpless AD reaction owes its success to the presence of... 

Both resolution and Sharpless asymmetric dihydroxylation were successful in the synthesis of Crixivan but the best method is one v e shall keep till later. Only one stereogenic centre remains, and its stereoselective formation turns out to be the most remarkable reaction of the whole synthesis. The centre is the one created in the planned enolate alkylation step,... 

R,R-diphenyl ethylene carbonate CR,R-DPEC)) with a racemic zirconaaziridine. (C2-symmetric, cyclic carbonates are attractive as optically active synthons for C02 because optically active diols are readily available through Sharpless asymmetric dihydroxylations [67].) Reaction through diastereomeric transition states affords the two diastereomers of the spirocyclic insertion product protonolysis and Zr-mediated transesterification in methanol yield a-amino acid esters. As above, the stereochemistry of the new chiral center is determined by the competition between the rate of interconversion of the zirconaaziridine enantiomers and the rate of insertion of the carbonate. As the ratio of zirconaaziridine enantiomers (S)-2/(R)-2 is initially 1 1, a kinetic quench of their equilibrium will result in no selectivity (see Eq. 32). Maximum diastereoselec-tivity (and, therefore, maximum enantioselectivity for the preparation of the... 

AD) and the application of a catch-and-release procedure using a supported boronic acid to effect in-line purification of the diol 20 (Scheme 5). The enantiomer of 20 could readily be obtained through the use of AD-mix-p in the Sharpless asymmetric dihydroxylation reaction. The two alcohol groups of the diol could subsequently be differentiated using an enzymatic selective protection. 

Oxidation of chroman-4-one and its thio analogue with Mn(OAc)3 gives the 3-acetates and subsequent basic hydrolysis yields the 3-hydroxychroman-4-one. Enzymatic hydrolysis of the 0-heterocycle using Amano PS lipase in a phosphate buffer selectively cleaved the (+)-isomer <03TA1489>. Enol ethers derived from chroman-4-one are converted into the 3-hydroxy-chromanone with high enantioselectivity, optimal with the pentyl ether, using a modified Sharpless asymmetric dihydroxylation reaction <03JOC8088>. 

In the concluding steps, manipulation of the furan ring of 89 gave 90 as a mixture of positional isomers. These were collectively converted to the unsaturated diol 91. The last crucial step, installation of two hydroxyl groups on the double bond, was achieved using a standard osmylation reaction [84]. In a second approach for the same step, the Sharpless asymmetric dihydroxylation of 91 was used and yielded one diastereoisomer 92 almost exclusively [85]. This second approach concluded with the synthesis of a lactone containing all correct stereocenters of the squalestatin core with the exception of that at C6. 

An efficient asymmetric total synthesis of L-fructose combines the Sharpless asymmetric dihydroxylation with an enzyme-catalyzed aldol reaction. L-Glyceraldehyde, prepared from acrolein, is condensed to DHAP in a buffered water suspension of lysed cells of KI2 Escherichia coli containing an excess of L-rhamnulose-1-phosphate (Rha) aldolase E. coli raised on L-rhamnose as sole carbon source). The L-fructose phosphate obtained is hydrolyzed to L-fructose with acid phosphatase. Similarly, the RAMA-catalyzed condensation of D-glyceraldehyde with DHAP,... 

This procedure provides a good method for the construction of l,2-a ft-aldol moieties that are less accessible by the Sharpless asymmetric dihydroxylation (see Scheme 37,0 Scheme 58, O Scheme 92,0 Sect. 11) [138] because the corresponding Z-oleflns are difficult to obtain and show reduced enantioselectivity. The first demonstration of the use of the biologically significant substrate dihydroxyacetone as a donor in organocatalyzed aldol reaction was reported by Barbas 111 and co-workers [139]. The reactions of DHA with protected glyoxal and glycer-aldehydes, in aqueous media and in the presence of enantiomerically pure diamine 24, provide access to pentuloses and hexuloses, respectively (O Scheme 19). 

Phenylalanine-derived oxazolidinone has heen used in O Scheme 52 as a chiral auxiliary for as)rmmetric cross-aldolization (Evans-aldol reactions [277,278,279,280,281,282,283,284, 285]). The 6-deoxy-L-glucose derivative 155 has heen prepared by Crimmins and Long [286] starting with the condensation of acetaldehyde with the chlorotitanium enolate of O-methyl glycolyloxazohdinethione 150. A 5 1 mixture is obtained from which pure 151 is isolated by a single crystallization. After alcohol silylation and subsequent reductive removal of the amide, alcohol 152 is obtained. Swem oxidation of 152 and subsequent Homer-Wadsworth-Emmons olefination provides ene-ester 153. Sharpless asymmetric dihydroxylation provides diol 154 which was then converted into 155 (O Scheme 60) (see also [287]). 

Moitessier, N., Henry, C., Len, C., Chapleur, Y. Toward a Computational Tool Predicting the Stereochemical Outcome of Asymmetric Reactions. 1. Application to Sharpless Asymmetric Dihydroxylation. J. Org. Chem. 2002, 67, 7275-7282. 

Equation 12.16 is an example of the Sharpless-Katsuki asymmetric epoxi-dation of allylic alcohols, which is catalyzed by a Ti complex bound to a chiral tartrate ligand.38 A Mn-salen39 complex serves as catalyst for asymmetric epoxi-dation (Jacobsen-Katsuki reaction) of a wide variety of unfunctionalized alkenes, shown in equation 12.17.40 0s04 complexed with chiral alkaloids, such as quinine derivatives (equation 12.18), catalyzes asymmetric 1,2-dihydroxylation of alkenes (known as the Sharpless asymmetric dihydroxylation).41 The key step of all these transformations is the transfer of metal-bound oxygen, either as a single atom or as a pair, to one face of the alkene. 

These furfliryl alcohols can be produced in either enantiomeric form via asymmetric catalysis. Our preferred method for the asymmetric synthesis of these fiiran alcohols 4.2 is by the highly enantioselective Noyori reduction of achiral acylfurans 4.1 (Scheme 4). Alternatively fiirfurly alcohols like 4.4 can be prepared by the Sharpless asymmetric dihydroxylation of vinylfuran 4.3. Key to this later approach was the recognition that vinylfuran 4.3 could be made by a Petersen olefination reaction. 

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