1.2- Diols from 0,7-epoxy alcohols

Red-Al first generates one equivalent of hydrogen gas from epoxy alcohols A (Figure 17.43). An O—A1 bond forms in the resulting trialkoxyaluminate D. The epoxy fragment in D then is reduced via an intramolecular reaction. The transfer of a hydride ion from aluminum leads selectively to the formation of a 1,3-diol, since the approach path that would lead to the 1,2-diol cannot be collinear to the C—O bond that would have to be broken (stereoelectronics , cf. Section 2.4.3). 

Although the Sharpless asymmetric epoxidation is an elegant method to introduce a specific defined chirality in epoxy alcohols and thus, in functionalized aziridines (see Sect. 2.1), it is restricted to the use of allylic alcohols as the starting materials. To overcome this limitation, cyclic sulfites and sulfates derived from enantiopure vfc-diols can be used as synthetic equivalents of epoxides (Scheme 5) [12,13]. 

The asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

Amino-1 J-diols.1 This reagent can be used as an equivalent of NH3 in a synthesis of 2-amino-l,3-diols from chiral 2,3-epoxy alcohols. Thus reaction of the... 

Another regioselective addition to an epoxide was used as one step in a synthesis of the r-butyldiphenylsilyl ether (7) of verrucarinic acid from 5.3 The diol was converted into the optically active epoxy alcohol by the Sharpless method (10, 64-65) and then oxidized to the epoxy acid 6 by the new ruthenium-catalyzed oxidation of Sharpless et al. (this volume). This epoxy acid undergoes almost exclusive / -addition with trimethylaluminum to give the desired product 7. 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

Chiral a-methyl aldehydes. Reaction of optically active 2,3-epoxy alcohols with AI(CH,)i results in a mixture of two diols that arc not separable by conventional chromatography. However, the 1,2-diol is oxidized by NaI04 to a chiral a-methyl aldehyde, which is easily separated from the 1,3-diol. 

By analogy to the halolactonization reaction, the synthesis of cyclic iodocarbonates has been studied with the aim of functionalizing a double bond under regio- and stereocontrol, starting from allylic or homoallylic alcohols. These heterocyclic intermediates are employed for the synthesis of epoxy alcohols, diols and triols. 

Epoxy alcohols react with Et2AlN3 under mild reaction conditions to afford 3-azido-l,2-diols resulting from the regio- and stereoselective attack of the nucleophile at the C-3 carbon of the epoxides [121]. Here the high regioselectivity observed with both cis- and trans-substituted epoxides is not affected by bulky substituents at C-3 (Sch. 85). 

The reverse regiocontrol, giving 1,2-diols, is observed with DIBAL-H (diisobutylaluminum hydride). The remarkable effect of titanium tetraisopropoxide as an additive to lithium borohydride has also been reported. In this reaction benzene is a better solvent than THF, probably because a Ti complex using both oxygens in epoxy alcohols is formed in benzene before the hydride attack. Other metal hydrides used include sodium hydrogen telluride (NaHTe) and an ate complex derived from DIBAL-H and butyllithium, both of which reduce epoxides to alcohols, although they have been tested with only a small number of examples. In the former case the reaction may proceed via a 2-hydroxyalkyltellurol intermediate. 

The second compound could be made by a Wittig reaction with a stabilized ylid and the required diol ikdehyde derived from an epoxy-alcohol and hence from an allylic alcohol by Sharpless epoxidation. 

Reduction of 2,3-epoxy alcohols with Red-Al [sodium bis(2-methoxyethoxy)alu-minum hydride] cleaves the C(2)-0 bond to furnish a 1,3-diol. The observed regiose-lectivity may result by an intramolecular delivery of hydride from the aluminate formed on reaction of Red-Al with the -CH2OH group. 

Attempted peroxy acid epoxidation of the bicyclic ketone (31 equation 13) gave the lactone (33), instead of several possible rational alternatives. The epoxide (32) was implicated as an intermediate when it was independently synthesized from the epoxy alcohol, and shown to give (33) on treatment with aqueous acid.- A mechanism involving scission of the acyl bridgehead bond via the hydrated 1,1 -diol form of the ketone was proposed to account for the formation of this unexpected product. The rearrangement of the isolongifolene derivative (34 equation 14) appears to be mechanistically related. The product (35) is formed by brief treatment with dilute HCIO4 in dioxane as a mixture of isomers believed to arise by acid-catalyzed epimerization of the carbinol center. ... 

Corey prepared the (6E,10Z)-LTB4 (115) from the previously described epoxy alcohol LTB4 synthon 119. Acid-catalyzed rearrangement of the derived phenylcarbonate 120 followed by protection, reductive cleavage of the vicinal carbonate, and cleavage of the resulting diol gave (2E)-r-butyldimethylsilyloxy-... 

Our retrosynthetic analysis is shown in Scheme 18. Retro-Wittig reaction leads to aldehyde 105 which is generated from alcohol 106 by Swem oxidation. This tetrahy-drofuran system might be generated by ring closure of epoxy alcohol 107 although this would involve an SN2 type attack of the hydroxyl function at the more hindered position of the epoxide. The diol unit in 107 was to be created by osmylation of an allylic alcohol as represented by precursor 108 (8). 

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