Regiodivergent Ring Opening Reactions of 2-Arylated 3-Nitrocyclopropane-1,1-dicarboxylates Leading to Polyfunctionalized Dipoles

Abstract

Two kinds of Lewis acid induced ring-opening reactions of 2-aryl-3-nitrocyclopropane-1,1-dicarboxylates proceeded to afford 5-aryl-2-isoxazolines and γ-keto acid derivatives, respectively. Different ring-opening modes could be controlled by choosing the ligand or solvent.

First synthesis of acylated nitrocyclopropanes

“…We commenced our study using ethyl acetoacetate ( 3c ) as starting 1,3-dicarbonyl compound according to method b ( Scheme 2 ). After heating an acetonitrile solution of 3c , N -bromosuccinimide, and p -toluenesulfonic acid [ 7 ], α-bromoacetoacetate 6c was isolated with a 44% yield after purification of the reaction mixture by silica gel column chromatography ( Scheme 3 ). In the subsequent reaction of the α-brominated product 6c with nitrostyrene 2a in the presence of triethylamine, the complete consumption of 2a was confirmed, however, the reaction mixture was complicated, and the desired cyclopropane 1c was not detected ( Scheme 3 ).…”

“…When a solution of 1e and tin(II) chloride in benzene was heated at 100 °C for 14 h, successive ring-opening/ring-closure proceeded, to produce furan 13 with a 46% yield ( Scheme 6 ). The coordination of two carbonyl groups to the tin species facilitated the ring opening of the cyclopropane ring to afford betaine [ 7 ], then the oxygen atom of the enolate attacked the benzyl cation to construct a five-membered ring. The subsequent elimination of nitrous acid, accompanied by aromatization, yielded furan 13 .…”

“…The latter compounds are highly reactive and undergo reaction with, e.g., mercaptoacetaldehyde affording thiophenes (reaction c) [ 5 ] or with activated (hetero)aromatic compounds to give diarylated (oxoalkyl)malonates [ 6 ]. In the reaction using tin(II) chloride as the Lewis acid, the ring opening and nucleophilic attack of the nitro group occur, to produce functionalized isoxazolines (reaction d) [ 7 ]. In contrast, denitration under basic conditions generates highly reactive allenes (reaction e), which serve as synthetic intermediates for polyfunctionalized enynes [ 8 ].…”

“…β-Nitrostyrene 2 serves as an appropriate acceptor for conjugate addition by diethyl malonate ( 3a ) to afford adduct 4a , in which the methine group flanked by two carbonyl groups is readily halogenated, and the subsequent intramolecular nucleophilic substitution by nitronic acid furnishes cyclopropane 1a (method a) [ 1 , 4 , 12 – 13 ]. Halogenated malonate 6a [ 7 , 14 – 17 ] and nitrostyrene 7 [ 18 ] can also be used as substrates in this protocol (methods b and c, respectively). In these methods, diesters are mostly used as 1,3-dicarbonyl compounds, with acetylacetone 3b used in only three cases [ 12 – 13 19 ], to the best of our knowledge.…”