One‐Pot Asymmetric Oxidative Dearomatization of 2‐Substituted Indoles by Merging Transition Metal Catalysis with Organocatalysis to Access C2‐Tetrasubstituted Indolin‐3‐Ones

Abstract

A one-pot approach for the asymmetric synthesis of C2-tetrasubstituted indolin-3-ones from 2substituted indoles was developed via merging transition metal catalysis with organocatalysis. This strategy involves two processes, including CuI catalyzed oxidative dearomatization of 2-substituted indoles using O 2 as green oxidant, and followed by an proline-promoted asymmetric Mannich reaction with ketones or aldehydes. A series of C2-tetrasubstituted indolin-3-ones were obtained in 35-86% yields, 2:1-> 20:1 dr and 48-99% ee. Moreover, the synthetic 2-tetrasubstituted indolin-3-ones could be easily transformed into 1H-[1,3] oxazino [3,4-a]indol-5(3H)-ones via a [4 + 1] cyclization process. In addition, the synthetic compound 3 s show certain antibacterial activity against S. aureus ATCC25923 and multi-drug resistance bacterial strain of S. aureus (20151027077) and its MIC values up to 8 μg/mL and 16 μg/mL, respectively.

A solid-supported organocatalyst for asymmetric Mannich reaction to construct C2-quaternary indolin-3-ones

“…In general, the desired C2-quaternary indolin-3-one products 11a–11o and 12a–12d were obtained with up to 83% yields, >20 : 1 dr and 99% ee, the absolute configuration and structure of 12d was unambiguously confirmed by single-crystal X-ray crystallography ( Table 3 ). 16 The reactions of 9a with aldehydes proceeded smoothly, affording the corresponding 2,2-disubstituted indolin-3-ones (11a–11e) in 48–82% yield with 6.3 : 1–11 : 1 dr and 77–98% ee. However, the slightly lower yield and poor ee was obtained for products 11e may be due to the steric interaction of isobutyraldehyde.…”

“… 9 Because of its importance in structure and biological activity, there has been extensively studied on the synthetic methods of these valuable C2-quaternary indolin-3-one skeletons. 9 e – i ,10–15 Till now, some asymmetric synthesis of C2-quaternary indolin-3-ones have been developed from 2-substitued indoles 15 or indolin-3-ones 11–13 as substrates, including our recently developed the combinatorial catalysis of transition metal and organocatlysis to synthesize C2-quaternary indolin-3-ones from 2-substitued indoles, 16 however, most of them require proline as an organocatalyst for this asymmetric Mannich reaction but none of them has been investigated in its solid-supported format to improve this asymmetric Mannich reaction yet ( Scheme 1 ). Therefore, to construct diverse C2-quaternary indolin-3 ketone compounds, it is necessary to further develop environmentally friendly and sustainably solid-supported organocatalysts for this asymmetric Mannich reaction.…”

Electrochemical Oxidative Addition of Nucleophiles on 2-Arylindoles: Synthesis of C2-Heteroquaternary Indolin-3-ones

“… − This unit has also been applied as a starting material to access complex polycyclic heterocycles. − In addition, the related compounds have displayed exciting applications in optoelectronic and material science in recent years. − Due to the high synthetic and biological importance of C2-quaternary indoline-3-ones, several methods have been developed . More firmly, these methods can be broadly divided into two main categories: (i) chemoselective nucleophilic addition to preformed 2-arylindole-3-one, an activated cyclic C-acylimine (path 1, Scheme a), − and (ii) direct oxidative dearomative transformations on 2-arylindoles with various nucleophiles (path 2, Scheme a). − Additional methods − that mainly involve transition metal-catalyzed transformations − and photooxidative rearrangements − have also been developed to access this unit. Despite these existing methods, creating a more general strategy for accessing 2,2-disubstituted indolin-3-ones from 2-substituted indoles under mild conditions is highly attractive.…”

Gold-catalyzed redox cycloisomerization/nucleophilic addition/reduction: direct access to 2-phosphoryl indolin-3-ones

“…1). 1,2 Due to their fascinating structures and promising biological activities, much attention has been paid to the construction of various 2,2-disubstituted indolin-3-ones, among which oxidative rearrangement of 2,3-disubstituted indoles, 3 direct conversion reaction of 3 H -indol-3-ones or indolin-3-ones, 4 and oxidative dearomatization 5 represent the main synthetic routes from cyclic starting materials.…”