Epoxy alcohols, chiral, ring opening

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

Chiral amino alcohols can be prepared by reaction of chiral epoxides with amines. Enantiopure (25, 3.R)-2,3-epoxy-3-phenylpropanol anchored to Merrifield resin has been used for ring-opening with secondary amines in the presence of lithium perchlorate to afford polymer-supported chiral amino alcohols 47 (Eq. 18) [56], By analogy, (2i ,35)-3-(cis-2,6-dimethylpiperidino)-3-phenyl-l,2-propanediol has been anchored to a 2-chlorotrityl chloride resin (48). Although this polymer had high catalytic activity in the enantioselective addition of diethylzinc to aldehydes, the selectivity of the corresponding monomeric catalyst was higher (97 % ee) in the same reaction. 

Thompson, D.H., Svendsen, C.B., MegUo, C.D. and Anderson, V.C. (1994) Synthesis of chiral diether and tetraether phospholipids regiospecific ring opening of epoxy alcohol intermediates derived from asymmetric epoxidation. The Journal of Organic Chemistry, 59, 2945-2955. 

Both open chain and cyclic epoxy alcohols can be neatly transformed into the corresponding epoxy ketones with high conversions and yields using just 1.1-1.5 equiv of DDO oxidant. Also, the conversion of optically active epoxy alcohols into epoxy ketones occurs selectively leaving the configuration at the chiral center(s) at the oxirane ring unaffected. ... 

Schomaker et al found that the Payne rearrangement is useful for controlling the regioselectivity of the reaction of dimethylsulfoxonium ylide with the epoxy alcohol 22. Thus the rearrangement of chiral non racemic epoxy alcohol 21 led to the more sterically accessible terminal epoxide 22, which then underwent nucleophilic epoxide opening with the ylide at C-1 to afford bis alkoxide 23. The 5-exo-tet ring closure of 23 resulted in the formation of 2,3-disubstituted tetrahydrofuran ring 24. 

In a collaborative project, the research groups of Masamune and Sharpless have described a new approach to the synthesis of sugars which features (i) titanium-catalysed asymmetric (Sharpless) epoxidation of allylic alcohols and (ii) stereoselective ring-opening of the resulting 2,3-epoxy-alcohols, viz (171), to chiral... 

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... 

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. ... 

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