Chiral compounds epoxy alcohols

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

The synthetic utility of chiral epoxy alcohol synthons produced by the Sharpless asymmetric epoxidation has been demonstrated in enantioselective syntheses of many important compounds. 

Chiral compounds (Continued) epoxy alcohols, 141 formulas, xiii xvii hydroxystannanes, 318 liquid crystals, 350 molecular lattics, 347 natural, 1 NMR spectra, 282 olefins, 173 oxetanones, 326 phenols, 287 see also Binaphthol phenylbutenes, 172 protonating agents, 324 sulfoxides, 159 sulfur ylides, 328 synthesis, I... 

Let s take these three chiral synthons in turn. First, the simplest one the central epoxide. The reagent we need here will carry a leaving group, such as a tosylate, and it can easily be made from the epoxy-alcohol. This gives a very good way of making this compound as a single enantiomer—a Sharpless asymmetric epoxidation of ally] alcohol. 

Owing to our interest in chiral synthons as C5-epoxy alcohols which are valuable building blocks for vitamins and other biologically active compounds, we investigated the enantioselective epoxidation of C5-allylic alcohols and tried to transform the products obtained into other homochiral C5-synthons. Until now, such oxygen-functionalized C5-compounds have been prepared starting from natural products by chiral-pool syntheses. 

The encouraging result of the trans-epoxy acylates with the chiral spiro compounds was appUed to the optically active system (Scheme 15). Asymmetric reduction of the enone 31 by Corey s method [72] afforded the allyl alcohol (-)-34 (90% ee). Epoxidation of (-)-34 by the stereoselective Sharpless epoxidation [73] afforded the cts-epoxy alcohol, cfs-(-)-35, as the sole product. The Mitsunobu reaction [74] of czs-(-)-35 with benzoic acid gave the trans-epoxy benzoate, trans- -)-36, (90% ee) in 89% yield. Treatment of trans-(-)-36 with BF3-Et20 afforded the optically active spiro compound (+)-37 in 89% yield with retention of the optical purity (90% ee). This means that the rearrangement occurs stereospecifically. The optically pure epoxy camphanate (-)-38 could be obtained after one recrystallization of the crude (-)-38 (90% de), which was obtained by the Mitsimobu reaction of cfs-(-)-35 with D-camphanic acid. The optically pure spiro compoimd (+)-39 (100% de) was obtained from the optically pure (-)-38 in 89% yield. 

There is a rough correlation between the enantiomeric excess observed for these epoxy alcohols and the steric complexity at the a-carbon of the C-3 substituent. When the C-3 substituent is a primary group (Table 5, entries 1,2,4,6-12 and 19-21), enantiofacial selectivity is highest and enantiomeric excesses of 80-95% are observed for these compounds. When the substituent is secondary (entries 3 and 15-18) or tertiary (entry 5), enantiofacial selectivity is much more variable. When the substituent is asymmetric, enantiofacial selectivity depends on the al lute configuration, as is evident in comparison of entry 15 with 16 and of 17 with 18 in Table 5. Epoxidation of these chiral allylic alcohols with one antipode of catalyst yields moderate to good diastereoselectivity, while with the odier antipode diastereoselectivity is virtually lacking. 

Compounds of this general structure are extremely useful and versatile synthons because combined in one molecule are an epoxide functional group (a highly reactive electrophilic site), an alcohol functional group (a potentially nucleophilic site), and at least one chirality center that is present in high enantiomeric purity. The synthetic utility of chiral epoxy alcohol synthons produced by the Sharpless asymmetric epoxidation has been demonstrated over and over in enantioselective syntheses of many important compounds. Some examples include the synthesis... 

Chakraborty TK, Purkait S, Das S. Synthesis of chiral 4-hydroxy-2,3-unsaturated carbonyl compounds from 3,4-epoxy alcohols by oxidation appHcation in the formal synthesis of macrosphelide A. Tetrahedron 2003 59 9127 9135. 

So, we were able to prepare selectively syn and anti trifluoromethyl amino alcohols. The next step was a search for a chiral approach to these compounds. Two approaches have been investigated to obtain chiral anti amino alcohols first we performed the reaction of epoxy ethers 3 with the chiral dimethylaluminum amide, prepared from the fi -phenethylamine and MeaAl (Scheme 5). From 3a, the reaction was effective leading, after reduction to the anti diastereoisomers 8a and 9a stereoselectively (Scheme 5). However, the chiral amine induced no selectivity anti amino alcohols 8a and 9a were obtained in a 50/50 mixture. Their separation was performed by crystallisation of the mandelate salts. Although this access to homochiral anti amino alcohols is somehow tedious, it is general since oxirane ring opening is efficient whatever the R substituent, and since epoxy ethers, substituted with various fluoroalkyl groups, are available. ... 

A novel approach to the asymmetric synthesis of epoxides, allylic alcohols, a-amino ketones, and a-amino aldehydes from carbonyl compounds through a,/i-epoxy sulfoxides using the optically active p-tolylsulfmyl group to induce chirality./. Org. Chem. 1989, 54, 3130-3136. 

Recently an improvement in this separation technique was reported, which seemed to indicate that enantioselective inclusion in the lattices of chiral hosts could be employed on a large scale. [11] When crystalline hosts such as R,R)-(-)-S (m.p. 196 °C), [12] (/ ,/ )-(-)-9 (m.p. 165 °C), [12] and (5,5)-(-)-10 (m.p. 128 °C) are suspended in hexane or water, chiral guest molecules form the same inclusion compounds as from solution. This is by no means self-evident, since inclusion compounds have different crystal lattices than the pure host crystals. Thus crystal/liquid reactions occur, and phase rebuildings analogous to those observed in gas/solid reactions [13] must take place. Yet this suspension technique is more selective and more effective than the initially developed solution technique. Numerous racemic alcohols like 11, -hydroxy esters like 12, epoxy esters like 13, and epoxy ketones like 14 were stirred a few hours with appropriate hosts (suspensions of 8, 9, and 10) and formed 1 1 complexes that could be filtered off in yields of > 85 % and with ee values of > 97 % (the complex of 12 and 9 formed in hexane only 80% ee in one step). Recrystallization of the inclusion... 

Oxiranecarboxylic acids 41 (glycidic acids) can be converted into a,P epoxy diazomethyl ketones 42 via mixed anhydrides. It was found that photolysis of these compounds in the presence of alcohols gave yhyunsaturated esters 44. It is thought that nucleophilic attack of the alcohol on the ketene 43 results in epoxide ring opening. The E olefin isomer is predominately formed, although small quantities of Z esters are also isolated (< 10%). Conveniently non-racemic, chiral substrates are readily prepared via Sharpless asymmetric epoxidation of allylic alcohol 39, followed by... 

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