Silver‐Catalyzed Dearomative [2π+2σ] Cycloadditions of Indoles with Bicyclobutanes: Access to Indoline Fused Bicyclo[2.1.1]hexanes**

Abstract

Bicyclo[2.1.1]hexanes (BCHs) are becoming ever more important in drug design and development as bridged scaffolds that provide underexplored chemical space, but are difficult to access. Here a silver‐catalyzed dearomative [2π+2σ] cycloaddition strategy for the synthesis of indoline fused BCHs from N‐unprotected indoles and bicyclobutane precursors is described. The strain‐release dearomative cycloaddition operates under mild conditions, tolerating a wide range of functional groups. It is capable of forming BCHs with up to four contiguous quaternary carbon centers, achieving yields of up to 99%. In addition, a scale‐up experiment and the synthetic transformations of the cycloadducts further highlighted the synthetic utility.

Synthesis of Sulfone Methylene-Substituted Indolines by Radical Cascade Cyclization of 2-Alkynylaniline Derivatives

“…Indolines can be synthesized via dearomatization of indoles, intramolecular Diels–Alder reactions, stereoselective syntheses, and a variety of catalytic synthetic pathways . Furthermore, new methods for the preparation of 2,3-disubstituted indolines have been attracting a great deal of research interest, providing efficient synthetic routes for the substituted indolines . Evano and co-workers reported the visible-light-mediated photocatalysis for the conversion of N -allyl- o -iodoanilines to indolines (Scheme a) .…”

Access to spiro-bicyclo[2.1.1]hexanes via BF3·Et2O-catalyzed formal [2π + 2σ] cycloaddition of bicyclo[1.1.0]butanes with benzofuran-derived oxa(aza)dienes

“…2 There has been a heightened emphasis on formulating efficient synthetic methodologies for BCHs, 3 and the [2π + 2σ] cycloaddition of bicyclo[1.1.0]butanes (BCBs) 4 with 2π-synthons emerges as a notable synthetic strategy due to its broad substrate compatibility and effectiveness. 5–7 Blanchard pioneered this approach in 1966 with the inaugural application of thermally driven [2π + 2σ] cycloadditions of BCBs with alkenes to yield captivating mono-BCHs. 5 a Very recently, the [2π + 2σ] cycloadditions 6 via a radical pathway between BCBs and alkenes have flourished, pioneered by Glorius 6 a and Brown.…”

“…6 b Furthermore, Leitch's 7 a study on Lewis acid catalyzed cycloaddition of imines and BCBs led to a rapid development of [2π + 2σ] dipolar cycloadditions. 7 These aforementioned elegant studies provided a variety of mono- or fused-BCHs (Scheme 1a). Despite the widespread usage of spirocycles in bioactive natural and synthetic compounds, 8 the synthesis of BCHs incorporating spirocycles has been constrained.…”