Synthesis and Application of Tertiary Allylic Nitro Compounds

Article abstract of DOI:10.1021/jo00289a024

A new procedure was developed for the synthesis of tertiary allylic nitro compounds.Secondary nitroalkanes (comprising nitrocyclohexane, 2-nitroheptane, 4-nitro-1-pentene, and 2-nitropropane) were treated with 1.5 equiv of electron-deficient acetylenes (including methyl propiolate, dimethyl acetylenedicarboxylate, and 3-butyn-2-one) to give the corresponding tertiary allylic nitro adducts in 62-90percent yields.These reactions required 5.0 equiv of potassium fluoride as the base, 1.0 equiv of tetra-n-butylammonium chloride as the phase-transfer catalyst, and dimethyl sulfoxide as the solvent.Tertiary allylic nitro compounds were also synthesized by the double Michael addition of 1 equiv of primary nitroalkanes to 2 equiv of electron-deficient acetylenes in the presence of potassium fluoride, tetra-n-butylammonium chloride, and dimethyl sulfoxide.Thus, nitroethane and methyl 4-nitrobutyrate (5) individually reacted with3.0-3.5 equiv of methyl propiolate to give dimethyl 3-methyl-3-nitro-1,4-pentadiene-1,5-dicarboxylate (6) in 75percent yield and dimethyl 3-<2-(methoxycarbonyl)ethyl>-3-nitro-1,4-pentadiene-1,5-dicarboxylate (7) in 53percent yield, respectively.Furthermore, the double Michael addition proceeded well when two different Michael acceptors were added sequentially: acetylenes followed by electron-deficient alkenes.Reaction of nitroethane with 1.0 equiv of methyl propiolate or 3-butyn-2-one and then with 2.0 equiv of methyl vinyl ketone afforded (E)-methyl 4-methyl-4-nitro-7-oxo-2-octenoate 88) in 60percent yield and (E)-5-methyl-5-nitro-3-nonene-2,8-dione (9) in 52percent yield, respectively.Alkenes containing an electron-withdrawing substituent and an alkyl group at the α- or β-position were also employed in the double Michael addition; however, they must be used as the first Michael acceptor.Thus, nitroethane reacted with 1.0 equiv of ethyl methacrylate and then with1.5 equiv of methyl propiolate to give (E)-methyl 6-(ethoxycarbonyl)-4-methyl-4-nitro-2-heptenoate (10) in 41percent yield.In a similar reaction involving 2-cyclohexen-1-one, instead of ethyl methacrylate, a mixture of (E)- and (Z)-methyl 4-nitro-4-(3-oxocyclohexyl)-2-pentenoate (11) was obtained in 50percent yield.The newly developed double Michael addition was used as the key step in a total synthesis of (+/-)-norsolanadione, a biologically active terpenoid.