A new method for functionalizing α,γ‐dinitro compounds at the β‐position: application to the cyclization of β‐alkoxy‐α,γ‐dinitro compounds

Abstract

Treatment of 2,4-dinitropentane with bromine and sodium methoxide in methanol, affords formation of an ether product, 2,4-dibromo-3-methoxy-2,4-dinitropentane, in 59% yield as a mixture of three diastereomers. This observation has led to a general synthesis of 3-alkoxy-2,4-dibromo-2,4-dinitropentanes, obtained in 75-86% yield from 2,4-dibromo-2,4dinitropentane as the preferred reactant. 4-Bromo-2,4-dinitro-2-pentene has been identified as an intermediate in these reactions. The nitroalkene has been isolated and undergoes conjugate addition with alkoxides to afford the same ether products after brominative work-up. The nitroalkene undergoes conjugate addition with sodium azide to give 3-azido-2,4-dibromo-2,4-dinitropentane in 38% yield as a mixture of two isomers in which the (R*,R*) isomer predominates. Sequential treatment of 2,4-dibromo-2,4-dinitropentane with sodium methoxide followed by sodium iodide and acetic acid gives 3-methoxy-2,4-dinitropentane in 63% yield, the overall product of simple methoxylation of 2,4-dinitropentane. However, attempted complete debromination of 2,4-dibromo-3-methoxy-2,4-dinitropentane with excess sodium iodide and acetic acid results only in monodebromination to give 2-bromo-3-methoxy-2,4-dinitropentane in 86% yield. Likewise, 2-bromo-3-ethoxy-2,4-dinitropentane is formed in 93% yield from the ethoxy analog. A mechanistic rationale is offered for condition-specific removal of the second Br atom in these reactions. Treatment of 3-methoxy-2,4-dinitropentane with potassium acetate/iodine in dimethyl sulfoxide affords formation of 4,5-dihydro-3,4-dimethyl-3-methoxy-4-nitroisoxazole 2-oxide in 30% yield as a single diastereomer. Conversion of 2-bromo-3methoxy-2,4-dinitropentane in 15% yield to 4,5-dihydro-3,4-dimethyl-3-methoxy-4-nitroisoxazole 2-oxide is also possible by using potassium acetate in dimethyl sulfoxide. The mechanistic pathways for formation of 4,5-dihydro-3,4-dimethyl-3methoxy-4-nitroisoxazole 2-oxide apparently involve unstable 3-methoxy-1,2-dimethyl-1,2-dinitrocyclopropane as the common intermediate. Similarly, 2-bromo-3-ethoxy-2,4-dinitropentane affords 4,5-dihydro-3-ethoxy-3,4-dimethyl-4nitroisoxazole 2-oxide in 13% yield. a 0.1 M NaOMe. b 0.1-0.24 M NaX. c 1.7 M NaOMe. d 0.8 M NaOCH 2 Ph. e 0.15 M NaN 3 and 0.03 M NaOEt β-ALKOXY-α,γ-DINITRO COMPOUNDS

Recent Advances in the Synthesis and Chemistry of Nitronates

“…29 A cyclization-rearrangement sequence was observed for dinitro compounds 41, albeit the yield of nitronates 42 was rather low (Scheme 13). 35 Scheme 12 Synthesis of nitronates 40 via a cyclopropanation-rearrangement sequence…”