A [3 + 2] Dipolar Cycloaddition Route to 3-Hydroxy-3-alkyl Oxindoles: An Approach to Pyrrolidinoindoline Alkaloids

Abstract

A [3 + 2] cycloaddition approach to the 3-hydroxy-3-alkyl oxindole scaffold is described. Isoxazolines obtained by cycloaddition of nitrile oxide 3 with 3-methylene oxindoles were elaborated to 3-hydroxy-3-cyanomethyl oxindoles employing a one-pot protocol en route to the pyrrolidinoindoline moiety which is found in many natural products. The total syntheses of alkaloids (±)-alline and (±)-CPC-1 were achieved using this methodology.

A Short and Flexible Synthetic Approach to the Naturally Occurring Racemic Neoclausenamide and Its Analogs

“…in acetone at 0 ℃, as described by Shi and coworkers, [8e] led only to the isolation of the self-aldol condensation product of acetone. Other selective methylation conditions [16] were also tried without success. The failure for selective N-methylation prompted us to recognize the difference between our substrates, characterizing by two secondary hydroxyl groups in 9, and those reported in the literature.…”

Mechanism and Regioselectivity of 1,3‐Dipolar Cycloaddition of Nitrile Oxides to 3‐Methylene Oxindole: A Density Functional Theory Study

“…They are usually generated in situ by dehydrohalogenation of N ‐hydroxyiminoyl chloride in the presence of a base for easy dimerization to oxopyrimidine. Roth's group reported 1,3‐dipolar cycloaddition of nitrile oxides to methylene indolone to construct novel isoxazoline spiroadducts by a “one‐pot method” at room temperature (Scheme ) . Here, the main product is the 3,5‐substituted isoxazoline with regioselectivity greater than 20 : 1, and it can be used to construct tricyclic indole‐type natural molecules.…”

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

“…Yield 117 mg (0.36 mmol, 72%) (method A), dr 10 : 1, a mixture of inseparable (3R*,4 0 S*)-and (3S*,4 0 S*)-diastereomers. 1 (4-uoro-3-methylphenyl)magnesium bromide (7i) generated from 4-bromo-1-uoro-2-methylbenzene (376 mg, 2.00 mmol). Eluent for column chromatography: benzene.…”

“…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.…”