Alcohols, 2,3-epoxy regioselectivity

Reaction with epoxy aiochols-3 Epoxides formed from (E)-allylic alcohols react regioselectively with organoaluminum compounds to provide 1,2-diols with inversion at C j in high yield. 

Cyclization of epoxy alcohols. The regioselectivity of this cyclization is greatly influenced by molecular sieves. 

The oxirane ring in 175 is a valuable function because it provides a means for the introduction of the -disposed C-39 methoxy group of rapamycin. Indeed, addition of CSA (0.2 equivalents) to a solution of epoxy benzyl ether 175 in methanol brings about a completely regioselective and stereospecific solvolysis of the oxirane ring, furnishing the desired hydroxy methyl ether 200 in 90 % yield. After protection of the newly formed C-40 hydroxyl in the form of a tert-butyldimethylsilyl (TBS) ether, hydrogenolysis of the benzyl ether provides alcohol 201 in 89 % overall yield. 

A11 elegant application of the strategy based on the appropriate use of a 6-exo or 6-endo cyclization of a 5- or y-epoxy alcohol, respectively, to give corresponding adjacent or fused THP rings can be found in the regioselective synthesis of the ABC tris-THP core of thyrsiferol and venustatriol [29b]. 

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]. 

A synthetically useful diastereoselectivity (90% dc) was observed with the addition of methyl-magnesium bromide to a-epoxy aldehyde 25 in the presence of titanium(IV) chloride60. After treatment of the crude product with sodium hydride, the yy -epoxy alcohol 26 was obtained in 40% yield. The yyn-product corresponds to a chelation-controlled attack of 25 by the nucleophile. Isolation of compound 28, however, reveals that the addition reaction proceeds via a regioselective ring-opening of the epoxide, which affords the titanium-complexed chloro-hydrin 27. Chelation-controlled attack of 27 by the nucleophile leads to the -syn-diastereomer 28, which is converted to the epoxy alcohol 26 by treatment with sodium hydride. 

Treating ally lie and homoallylic epoxy alcohols with an equivalent amount of halogen (Br2, I2) in the presence of a stoichiometric amount of Ti(OPr )4 provides halohydrins under mild conditions with a high degree of generality and with good regioselectivity (Scheme 4-12).26... 

An alternative method for reducing 2,3-epoxy alcohols to 1,2-diols through regioselective delivery of hydride to C-3 is realized by treating the correspond-... 

When treated with organocuprates, 2,3-epoxy alcohols can be converted to substituted 1,3-diols with high regioselectivity and stereoselectivity. Thus, as... 

In the reaction of the conformationally restricted epoxy alcohol 84 and methyl or benzyl isocyanate, the epoxy carbamate 85 was formed. Cycliza-tion of 85 in tetrahydrofuran in the presence of sodium hydride gave the oxazinone 86 in approximately 20% yield, and the oxazolidinone 87 (R = Me, CH2Ph) in 40-60% yield. The formation of the two products can be rationalized by different nucleophilic attacks on the urethane nitrogen. With increasing nucleophilicity of the nitrogen, the regioselectivity of the reaction is shifted toward the formation of 87 (92TL3009). 

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