Organocatalytic Access to Enantioenriched Spirooxindole-Based 4-Methyleneazetidines

Abstract

This work describes the synthesis of enantioenriched spiro compounds, incorporating the azetidine and the oxindole motifs. The preparation relies on a formal [2 + 2] annulation reaction of isatin-derived N-tert-butylsulfonyl ketimines with allenoates. The asymmetric induction is secured by an organocatalytic strategy, exploiting a bifunctional cinchona-type β-isocupridine-based catalyst. Some post-transformation products, including unexpected spiropyrroline and 3,3-disubstituted oxindole derivatives, are also presented.

Asymmetric Catalytic Ketimine Mannich Reactions and Related Transformations

“…However, the ketimine variant was not known until 2013, in which three independent studies were disclosed [145][146][147]. One of them employed isatin-derived ketimines [146], and more contributions with isatin-derived ketimines were disclosed later (selected references; [148][149][150][151][152][153][154]). In light of the excellent review articles on the isatin-derived ketimines that covered up to the end of 2017 [73][74][75], we discuss a few selected examples in Section 6.3 (vide infra).…”

Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of Thietane 1,1-Dioxides

“… 3 In contrast, chiral, enantiopure analogues 3 are much less common. 4 In particular, there are no examples of enantiopure thietane 1,1-dioxide containing spirocycles 4 .…”

“…Four-membered-ring-containing spirocycles have become particularly attractive building blocks in drug discovery, with much attention placed on the development of synthetic routes to achiral ( 1 , Scheme A), as well as chiral but racemic ( 2 ) spirocycles . In contrast, chiral, enantiopure analogues 3 are much less common . In particular, there are no examples of enantiopure thietane 1,1-dioxide containing spirocycles 4 .…”

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

“…Going on with our interest in the synthesis of 3,3-disubstituted oxindoles [7][8][9][10][11] and also of aminoboronic acids [12], we recently exploited a molecular hybridization strategy to synthesize chiral oxindole-based β-aminoboronic acids and spiro derivatives [13]. Apart from our work and a quite recent report describing a useful Cu-catalyzed enantioselective intramolecular transformation [14], the insertion of a boron atom into chiral oxindoles is scarcely reported.…”