Enantioselective Synthesis of Quaternary 3‑Aminooxindoles via Organocatalytic Asymmetric Michael Addition of 3‑Monosubstituted 3‑Aminooxindoles to Nitroolefins

An enantioselective synthesis of quaternary 3-aminooxindoles with 3-monosubstituted 3-aminooxindoles as nucleophiles is first presented. A Michael addition reaction of 3-monosubstituted 3-aminooxindoles to nitroolefins has been developed with a bifunctional thiourea-tertiary amine as a catalyst to afford a range of 3,3-disubstituted oxindoles bearing adjacent quaternary-tertiary centers in good results (up to 98% yield, >99:1 dr, and 92% ee). We also demonstrate the potential synthetic utility of this methodology by a transformation of the product into a spirocyclic oxindole compound

Enantioselective Synthesis of Quaternary 3‑Aminooxindoles via Organocatalytic Asymmetric Michael Addition of 3‑Monosubstituted 3‑Aminooxindoles to Nitroolefins

An enantioselective synthesis of quaternary 3-aminooxindoles with 3-monosubstituted 3-aminooxindoles as nucleophiles is first presented. A Michael addition reaction of 3-monosubstituted 3-aminooxindoles to nitroolefins has been developed with a bifunctional thiourea-tertiary amine as a catalyst to afford a range of 3,3-disubstituted oxindoles bearing adjacent quaternary-tertiary centers in good results (up to 98% yield, >99:1 dr, and 92% ee). We also demonstrate the potential synthetic utility of this methodology by a transformation of the product into a spirocyclic oxindole compound

A Protocol for the Synthesis of CF₂H‑Containing Pyrazolo[1,5‑<i>c</i>]quinazolines from 3‑Ylideneoxindoles and in Situ Generated CF₂HCHN₂

Herein is disclosed a selective and facile approach for the construction of CF₂H-containing pyrazolo­[1,5-<i>c</i>]­quinazolines from easily accessible 3-ylideneoxindoles and in situ generated CF₂HCHN₂. The reaction involving a [3 + 2] cycloaddition/1,3-H shift/rearrangement/dehydrogenation cascade proceeded smoothly at room temperature in the absence of catalyst and additive. Moreover, this metal-free process along with mild conditions is desirable and valuable for the pharmaceutical industry. Importantly, this reaction features a broad substrate scope, good functional group tolerance, and gram-scale synthesis

A Protocol for the Synthesis of CF₂H‑Containing Pyrazolo[1,5‑<i>c</i>]quinazolines from 3‑Ylideneoxindoles and in Situ Generated CF₂HCHN₂

Herein is disclosed a selective and facile approach for the construction of CF₂H-containing pyrazolo­[1,5-<i>c</i>]­quinazolines from easily accessible 3-ylideneoxindoles and in situ generated CF₂HCHN₂. The reaction involving a [3 + 2] cycloaddition/1,3-H shift/rearrangement/dehydrogenation cascade proceeded smoothly at room temperature in the absence of catalyst and additive. Moreover, this metal-free process along with mild conditions is desirable and valuable for the pharmaceutical industry. Importantly, this reaction features a broad substrate scope, good functional group tolerance, and gram-scale synthesis

Tandem Michael Addition–Ring Transformation Reactions of 3‑Hydroxyoxindoles/3-Aminooxindoles with Olefinic Azlactones: Direct Access to Structurally Diverse Spirocyclic Oxindoles

An efficient method for the direct construction of two classes of spirocyclic oxindoles by the reactions of 3-hydroxyoxindoles/3-aminooxindoles and (<i>Z</i>)-olefinic azlactones through a tandem Michael addition–ring transformation process has been developed. With DBU as the catalyst, a range of spiro-butyrolactoneoxindoles and spiro-butyrolactamoxindoles, containing an oxygen or a nitrogen heteroatom, respectively, in the spiro stereocenter, were smoothly obtained with good to excellent diastereoselectivities in high yields

Asymmetric [3 + 2] Cycloaddition Reaction of Isatin-Derived MBH Carbonates with 3‑Methyleneoxindoles: Enantioselective Synthesis of 3,3′-Cyclopentenyldispirooxindoles Incorporating Two Adjacent Quaternary Spirostereocenters

A highly regio- and stereoselective [3 + 2] cycloaddition reaction for constructing novel 3,3′-cyclopentenyldispirooxindoles incorporating two adjacent quaternary spirostereocenters is reported. Under the mild conditions, the asymmetric annulation of isatin-derived MBH carbonates with 3-methyleneoxindoles involving a chiral tertiary amine catalyst provides the corresponding dispirooxindole frameworks with an extraordinary level of enantioselective control. Further synthetic utility of this method was demonstrated by the gram-scale experiment and simple transformation of the obtained product. Moreover, a plausible mechanism for this annulation reaction was also proposed on the basis of the control experiments

Asymmetric [3 + 2] Cycloaddition Reaction of Isatin-Derived MBH Carbonates with 3‑Methyleneoxindoles: Enantioselective Synthesis of 3,3′-Cyclopentenyldispirooxindoles Incorporating Two Adjacent Quaternary Spirostereocenters

A highly regio- and stereoselective [3 + 2] cycloaddition reaction for constructing novel 3,3′-cyclopentenyldispirooxindoles incorporating two adjacent quaternary spirostereocenters is reported. Under the mild conditions, the asymmetric annulation of isatin-derived MBH carbonates with 3-methyleneoxindoles involving a chiral tertiary amine catalyst provides the corresponding dispirooxindole frameworks with an extraordinary level of enantioselective control. Further synthetic utility of this method was demonstrated by the gram-scale experiment and simple transformation of the obtained product. Moreover, a plausible mechanism for this annulation reaction was also proposed on the basis of the control experiments

Organocatalytic Asymmetric Michael/Friedel–Crafts Cascade Reaction of 3‑Pyrrolyl-oxindoles and α<i>,</i>β‑Unsaturated Aldehydes for the Construction of Chiral Spiro[5,6-dihydropyrido[1,2‑<i>a</i>]pyrrole-3,3′-oxindoles]

An efficient and unprecedented organocatalytic asymmetric reaction of 3-pyrrolyl-oxindoles with α,β-unsaturated aldehydes to generate spirocyclic oxindole compounds was developed. The reactions were catalyzed by diphenylprolinol silyl ether and 2-fluorobenzoic acid via an asymmetric Michael/Friedel–Crafts cascade process, followed by dehydration with <i>p</i>-toluenesulfonic acid to afford a wide variety of structurally diverse spiro­[5,6-dihydropyrido­[1,2-<i>a</i>]­pyrrole-3,3′-oxindole] derivatives in high yields (up to 93%) and with high to excellent diastereo- and enantioselectivities (up to >99:1 dr and 97% ee)