Synthesis and characterization of chiral nitronic esters via O-alkylation of (4S*,5R)-(+)-4-(1'-nitro-1'-carbethoxymethyl)-5-[(1R)-menthyloxy]-3,4-dihydro-2(5H)-furanoae with alkyl halides

A series of stable and enantiomerically pure alkyl nitronic esters are synthesized in good to excellent yields via O-alkylation of (4S*,5R)-(+)-4-(1'-nitro-1'-carbethoxymethyl)-5-[(1R)-menthyloxy] -3,4-dihydro-2(5H)-furanone (4a) with alkyl halides in the presence of K2CO3 and DMF at room temperature. Thus, nitronic esters are obtained for the first time from the alkali metal salt of a nitro compound and various alkyl halides, which refutes the traditionally held view that the reaction of alkyl halides with alkali metal derivatives of nitro compounds gives a carbonyl compound and an oxime, rather than a nitronic ester. Secondary alkyl nitronic esters are found to partially decompose into O-alkyloximes. The configurations of the nitronic esters and O-alkyloximes were assigned to be Z on the basis of the NOE experiments. The synthesis of the nitro furanone 4a and its enolization to form a six-membered intramolecular hydrogen bond structure are described.