SYNTHESIS AND APPLICATION OF TERTIARY ALLYLIC NITRO-COMPOUNDS

A new procedure was developed for the synthesis of tertiary allylic nitro compounds. Secondary nitroalkanes (comprising nitrocyclohexane, 2-nitroheptane, 4-nitro-l-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 62-90% 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 with 3.0-3.5 equiv of methyl propiolate to give dimethyl 3-methyl-3-nitro-l,4-pentadiene-l,5-dicarboxylate (6) in 75% yield and dimethyl 3-[2-(methoxycarbonyl)ethyl]-3-nitro-l,4-pentadiene-l,5-dicarboxylate (7) in 53% 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 (8) in 60% yield and (E)-5-methyl-5-nitro-3-nonene-2,8-dione (9) in 52% yield, respectively. Alkenes containing an electron-withdrawing substituent and an alkyl group at the a- or the 0-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 with 1.5 equiv of methyl propiolate to give (E)-methyl 6-(ethoxycarbonyl)-4-methyl-4-nitro-2-heptenoate (10) in 41% yield. In a similar reaction involving 2-cyclohexen-l-one, instead of ethyl methacrylate, a mixture of (E)- and (Z)-methyl 4-nitro-4-(3-oxocyclohexyl)-2-pentenoate (11) was obtained in 50% yield. The newly developed double Michael addition was used as the key step in a total synthesis of (i)-norsolanadione, a biologically active terpenoid. © 1990, American Chemical Society. All rights reserved.