Ethyl α‐Nitrocinnamates in the Synthesis of Highly Functionalized Isoxazoles

Abstract

An effective method for the synthesis of highly functionalized isoxazoles from readily available starting ethyl α-nitrocinnamates has been developed. Ethyl α-nitrocinnamates react smoothly with α-nitro carbonyl compounds to produce isoxazoles in good yields. Michael addition of pyridinium ylides to ethyl α-nitrocinnamates can also produce these isox-

Condition‐Based Selective Synthesis of 3,4,5‐Trisubstituted Isoxazoline N‐oxides, 4,5‐Dihydroisoxazoles and Isoxazoles

“…Based on our previous work and Chuang's report, a plausible reaction mechanism was proposed as shown in Scheme . Henry reaction between the in situ generated methyl nitroacetate 9 and aldehydes 2 yielded α,β‐unsaturated nitroolefin 10 .…”

Synthesis of Trisubstituted Isoxazoles from Nitroenamines and Aromatic Aldehydes

“…When 1d (open-ring analogue of 1a) was applied, the reaction proceeded slowly and most substrate 1d remained unreacted after 48 h. Eventually, product 3r was obtained in 26% yield. Table 3 Reactions between nitroenamines and 4-bromobenzaldehyde Based on the intermediates (4, 5) obtained from the reactions above and the reported literature utilizing nitro-containing compounds to synthesize isoxazoles, [14] a plausible mechanism is proposed in Scheme 1. Fristly, under the catalysis of L-proline, a Lewis base, the nucleophilic reaction between 1a and 2a occurred to afford the intermediate 4, which generated during the reaction and expended eventually.…”

“…Due to its importance, dozens of methods for the construction of isoxazoles have been developed, including cyclization of benzaldoxime chloride with 1,3-dicarbonyl compounds, [6] cycloaddition of nitrile oxides to alkynes, [7][8][9] condensation of oxime dianions, [10] cyclization of propargylic oximes, [11,12] rearrangement of subsituted oxetanes, [13] and reaction of nitroacetates with dipolarophiles. [14] Although a number of methods are available as cited above, research for newer methods for the synthesis of various substituted isoxazoles is still of great significance to pharmaceutical and agricultural chemistry. Nitromethylene imidazolidine A ( Figure 2) has good insecticidal activity.…”

Cyclocondensation of Hydroxylamine with 1,3‐Bis(het)arylmonothio 1,3‐Diketones and 1,3‐Bis(het)aryl‐3‐(methylthio)‐2‐prop­enones: Synthesis of 3,5‐Bis(het)arylisoxazoles with Complementary Regioselectivity

“…In parallel strategies, Miyata and co‐workers have developed a practical synthesis of 3,5‐disubstituted isoxazoles by silver‐catalysed cyclization of O ‐benzylalkynyloxime ethers,10a along with a gold‐catalysed domino reaction of O ‐allylalkynyloxime ethers involving cyclization and subsequent Claisen‐type rearrangement to give trisubstituted isoxazoles in a highly regioselective manner 10b. Other recently published methods include the iodocyclization of N ‐alkoxycarbonyl‐ O ‐propargylic hydroxylamines;11a a sequential iron‐ and palladium‐catalysed transformation of propargyl alcohols into N ‐protected propargylhydroxylamines, and their subsequent cyclization and coupling with various aryl iodides to give trisubstituted isoxazoles in a multistep one‐pot reaction;11b base‐catalysed cyclocondensation of activated nitromethylene compounds with dipolarophiles;3c,12a–12c zinc‐triflate‐catalysed aerobic cross‐dehydrogenative coupling (CDC) of alkynes with nitrones;13a hypervalent‐iodine‐induced cycloaddition of nitrile oxides to alkynes;13b–13d N ‐heterocyclic‐carbene‐catalysed 1,3‐dipolar cycloaddition of nitrile oxides and alkynes;5f and dipolar cycloaddition of acetylenic boronates4g,14 and silaacetylenes5j with nitrile oxides. A completely regioselective synthesis of unsymmetrically 3,5‐disubstituted isoxazoles by the reaction of the 1,4‐dianions of oximes derived from α‐alkyl ketones with various amides/esters has also been described by Olofson15a,15b and others 15c.…”