Dipolar Cycloaddition of Chiral N- Alkoxyalkyl Nitrones

Proof for the stereocontrol exerted by the mercury atom has been obtained from the carbocychzation of methyl 4-0-benzoyl-2,3,6-trideoxy-a-D-g/yccro-hex-5-enopyranoside 119 (Fig. 8.34). 

Vasella [58] has shown that the hydroxy-oxime 122 (2,3-0-isopropylidene-5-0-trityl-D-ribose oxime) can be, via its tautomeric form a-alkoxy-hydroxylamine 123, converted by reaction with carbonyl compounds (formaldehyde, acetaldehyde, etc.) to N-(alkoxyalkyl) nitrones 124 which then reacts via 1,3-dipolar cycloaddition with methyl methacrylate to give the protected isoxazolidine ribosides 125, 126 epimeric at C5. This reaction proceeds in high yield (97 %) and with high stereoselectivity (84 16) (Fig. 8.35). 

The high stereoselectivity of cycloaddition of N-(alkoxyalkyl) nitrones obtained by the use of formaldehyde and acetone prompted Vasella to identify the factors that were responsible for this high stereoselectivity. 

The hydrolysis of isoxazolidine riboside 127 (Rj = H R2 = CH3) obtained by the hydrolysis of the C5 trityl group from 125, as well as of 128, obtained from detritylation of 126, both isoxazolidines 129 and 130 were obtained (Fig. 8.36). 

The only difference between the isoxazolidines 127 and 128 was the configuration at the C5 carbon. 

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