Saturated heterocyclic aldol reaction

For the reaction of fully saturated 1,3-dioxanes with electrophiles, an activation of the heterocycle by metalation either close to an appropriate functional group or by displacement of a functional group is necessary since deprotonation of unfunctionalized 1,3-dioxanes is not a common method. It was reported that 5-nitro-l,3-dioxanes were alkylated at C-5 using standard alkylation conditions (LDA, R-X) <2001TL105, 2006JOC2200> (Scheme 59) or by reaction with Michael acceptors <2002TL8351>. A 5-hydroxymethyl-5-nitro-l,3-dioxane was also amenable to alkylation after a photoinduced retro-aldol reaction had taken place in the presence of sodium methoxide. However, only 2-nitrobenzyl chloride was a suitable electrophile for an efficient alkylation <2004TL1737>. 

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