Efficient assembly of 3-substituted oxindole-based isoxazolines leading to the synthesis of (±)-flustraminol-B and related natural product building blocks

Water‐Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4‐Oxadiazoles

“…Abstract: Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However,t he present work revealed that water-assisted generation of nitrile oxides proceeds under mild acidic conditions (pH [4][5]. Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts,t hus yielding isoxazoles and isoxazolines,r espectively,w ith excellent stereoselectivity towardf ive-and six-membered cyclic alkenes.Adouble stereoselective cycloaddition of two units of an itrile oxide with cyclohexene was also achieved, thus yielding 1,2,4-oxadiazole derivatives having au nique hybrid isoxazoline-oxadiazole skeleton.…”

“…Therefore, the synthesis of isoxazolines and isoxazoles is carried out in solvents containing bases as catalysts. [1,5] However, isoxazolines and isoxazoles can also be prepared by other methods, for example,u sing transition-metal catalysts (ruthenium or palladium), [6] silver-mediated radical cyclization of ketoximes and 1,3-dicarbonyl compounds, [7] copper nitrate trihydrate as as ource of nitrile oxides, [8] copper-catalyzed oxyazidation of unactivated alkenes, [9] and an asymmetric hydroxylamine/ enone cascade reaction. [10] Cycloaddition of an itrile oxide and alkyne is also widely used in click chemistry,particularly for nucleic acids and materials chemistry, [11] and such acycloaddition is strictly performed either under basic conditions or using metal catalysts.Organic reactions in water can not only be considered green chemistry (abundance in nature and environmentally friendly solvent), but also have the advantage of being run in biological systems (e.g., click reactions, bioconjugation, and bioorthogonal chemistry).…”

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…Murrayanine (212) was derived from aldehyde 217 in three steps (Scheme 53). The two-step synthesis of murrayastine (218) was attained through the Pd-catalyzed Buchwald-Hartwig coupling followed by Pd-catalyzed oxidative coupling (Scheme 54). 94 A compact route to murrayaquinone A (212) was developed starting with 219 through a one-pot tandem Buchwald-Hartwig/C-H arylation-ring-closing sequence (Scheme 54).…”

Preparation of spiro[indole-3,5′-isoxazoles] via Grignard conjugate addition/spirocyclization sequence

“…Due to their diverse biological proles and important pharmaceutical activities, natural and synthetic spiroheterocycles have been the constant focus of attention of many research groups as synthetic targets. [1][2][3] Although the subjects of the present study, 4 0 H-spiro[indoline-3,5 0 -isoxazoles] and 4 0 Hspiro[indole-3,5 0 -isoxazoles], have not been found in nature, they share a privileged polycyclic framework with an array of highly potent natural products. 1,2,[4][5][6][7][8] The chemistry of related 4 0 H-spiro[indoline-3,5 0 -isoxazol]-2-ones (1) is much better known, and quite a few methods toward their synthesis have been developed to date.…”

“…[1][2][3] Although the subjects of the present study, 4 0 H-spiro[indoline-3,5 0 -isoxazoles] and 4 0 Hspiro[indole-3,5 0 -isoxazoles], have not been found in nature, they share a privileged polycyclic framework with an array of highly potent natural products. 1,2,[4][5][6][7][8] The chemistry of related 4 0 H-spiro[indoline-3,5 0 -isoxazol]-2-ones (1) is much better known, and quite a few methods toward their synthesis have been developed to date. Most of these employ readily available isatin precursors 2 as a synthetic platform (Scheme 1), and typically involve an acid-assisted 1,5-spirocyclization of monooximes of 3-ene-2,5-diones, 9,10 [3 + 2]-cycloaddition of nitrile oxides to 3-methyleneoxindoles, [11][12][13] or metal-catalyzed selective vinylation of isatin oximes with vinylboronic acids.…”