Dihydroxylation diastereoselective

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

Scheme 20. Synthesis of aldehyde 68 the diastereoselective dihydroxylation of 82 and synthesis of 87.

Chart 3.4 Proposed substrate-reagent assembly for the diastereoselective dihydroxylation of 55... 

Cyclohexenones 34 also undergo a highly diastereoselective dihydroxylation to give cii-diols 39 (Scheme 11).22 These diol amides are converted to hydroxylactones 40 by an acid-catalyzed process involving retro aldol-realdolization prior to transacylation. The enantiomers of hydroxylactones 40 are obtained from iodolactones 35 by iodide exchange with 2,2,6,6-tetramethylpiperidin-l-yloxy free radical (TEMPO) followed by reductive cleavage of the TEMPO derivative with Zn in ElOAc. The enantiomeric purity of the hydroxylactones prepared by either route is 95-98% ee. 

Additionally, 1,2-dihydroxyethylene dipeptide analogues without the C-terminal carboxylic acid have been used to obtain aspartyl proteases inhibitors.[641 These efforts include stereoselective alkylation of imines, one-pot reductive amination of epoxy ketones, ring opening of epoxides with sodium azide, diastereoselective dihydroxylation of allylic amines, and enzymatic resolution and stereocontrolled intramolecular amidation. 

The cyclic allylboronic acids are excellent substrates also for diastereoselective dihydroxylation. Scheme 7 demonstrates the utility of this reaction in preparing functionalized xylitol derivative 85 with >20 1 diastereoselec-tivity <2002AGE152>. 

For this MBFT, both a Diels-Alder and a dieniminium-enamine mechanism have been proposed to give rise to the scaffold. The preference for the cis products - regardless of the configuration of the input ( 7Z-acetoxy crotonalde-hyde) - however, suggests the involvement of the latter rather than the former. After cyclization, the product is amenable to diastereoselective dihydroxylation of the more distal alkene, followed by acetonide protection. The successive seven-step... 

A recent example L. Emmanuvel, T.M. A. Shaikh, A. Sudalai, Nal04 / LiBr-mediated diastereoselective dihydroxylation of olefins a catalytic approach to the Prevost-Woodward reaction, Org. Lett. 7 (2005) 5071-5074. 

Acetylide 241 combines smoothly with electrophiles, in particular, aldehydes (Scheme 1-186). The adducts can be subjected to enzymatic racemate resolution and then converted by Lindlar hydrogenation or reduction with sodium bis(2-methoxyethoxy)-aluminum hydride ("Red-Al") into the cis- and tram-allylic alcohol, respectively. After diastereoselective dihydroxylation with osmium tetroxide and protection of the 1-hydroxyl group 2,6-dideoxy-6,6,6-trifluoro sugars are obtained (Scheme 1-186). ... 

One of the foremost methods for oxidation of olefins is stereospecific syn-di-hydroxylation by treatment with OSO4. Because of the toxicity and cost of osmium, however, the need for methods that would employ substoichiometric quantities of this reagent was identified early on [180], A number of stoichiometric oxidants for catalytic dihydroxylations were examined, including metal chlorates, HjOa, NMO [181], f-BuOOH [182], and KjFeiCN) [40, 183], The mechanism of 0s04-catalyzed dihydroxylation reactions has been the subject of much debate details of these mechanistic considerations are beyond the focus of this book and are amply discussed elsewhere [40-42,47,49,184-186]. A number of interesting stereoselectivity trends of general importance in substrate-controlled diastereoselective dihydroxylations [40-43] and catalytic asymmetric dihydroxylations are discussed below (Section 9.8) [42, 44-49]. 

Another example was provided by Vedejs, who showed that the lone methine stereogenic center in cyclododecaene 252 imparts sufficient conformational control to lead to a highly diastereoselective dihydroxylation reaction (dr >20 1, Equation 43) [189]. 

In another study of 1,1-disubstituted olefins [200], Evans found that 299 participated in a highly diastereoselective dihydroxylation reaction (Scheme 9.38) [204]. The transformation afforded a 96 % yield of diol 300 as a single isomer, which served as a key intermediate in the synthesis of the macrolide antibiotic cytovaricin (301). 

Overman s discovery of the rearrangement of trichloroacetimidates [16, 39, 40] ushered in a powerful new method for the synthesis of alkaloids. A clever implementation of this transformation was reported in Danishefsky s synthesis of the antitumor agent pancratistatin (86, Scheme 16.9) [70]. Thermal rearrangement of imidate 84 led to amide 85, hence installing the key amine to become part of the lactam in the natural product and setting the stage for a subsequent diastereoselective dihydroxylation. 

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