Epoxidation of Glycals

The efficient epoxidation of glycals was reported in 1989 by Danishefsky [34, 39]. Since acyl protecting groups can participate in the ring opening reactions of the epoxide, they have to be replaced by ether or acetal functions. 

The uniquely generated 2 -hydroxyl group arising from opening of the 1,2-epoxide donor can therefore be exploited in the synthesis of 2-deoxy-P-glycosides [41]. Deoxygenation into 62 was accomplished by free radical reduction of the 2 - 

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Scheme 5.65 Summary of reaction outcomes in DMDO epoxidation of glycals.

The use of other peroxides in the epoxidation of glycals is limited by selectivities that are often inferior to those achieved with DMDO. One notable exception is the use of the wCPBA (m-chloroperbenzoic acid)/KF combination and its recent successful application in one-pot epoxidation alcoholysis (Scheme 5.66) [197]. This involved treatment of benzylated D-galactal 36 in dichloromethane/methanol with a mixture of wCPBA and KF (2 1) in anhydrous dichloromethane to give methyl-2-hydroxygalactoside 165. 

Epoxidation of glycals can be effected in almost quantitative yield by dimethyldioxirane in acetone at 0°. In the case of nonparticipating protecting groups, the a-epoxide is formed almost exclusively. These a-l,2-anhydro sugars react with alcohols with clean inversion to form P-glycosides.5... 

R. L. Halcomb and S. J. Danishefsky, On the direct epoxidation of glycals Application of a reiterative strategy for the synthesis of p-linked oligosaccharides, J. Am. Chem. Soc. 777 6656... 

The third extensively explored protocol involves the epoxidation of glycals by... 

Danishefsky formulated a strategy to staurosporine [41], in which epoxidation of glycal (-)-98 with maleimide 97 resulted in one of the indole N-glycosidic linkages to form 99. Treatment of olefin 99 using Barton deoxygenation, iodine and f-BuOK followed by radical dehalogenation provided the pyranosylated indolocarbazole 101 with 64% yield. Deprotection and methylation followed as shown in Scheme 14 (i.e., 101—102), after which reduction of imide 102 led to a 1 1 mixture of 1 and la. 

Epoxidation of glycal 134 with DMDO followed by in situ reduction of the pyrrole aldehyde and subsequent attack on the epoxide afforded the spiroacetal core of acortatarin B in high yield as a single diastereomer. Cleavage of the TlPS-ethers with TBAF then afforded the natural product 38 in excellent yield. 

Murray s finding that dimethyldioxirane (DMDO) can be readily prepared with acetone and oxone [54] allowed the development of epoxidation reactions under essentially neutral conditions [55]. Such DMDO oxidations were utilized by Danishefsky in an efficient direct epoxidation of glycals, as illustrated by the formation of epoxide 10 (dr >99 1, Equation 5) [56]. 

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