Cascade Reactions of Nitrones and Allenes for the Synthesis of Indole Derivatives

Abstract

Cascade reactions involving nitrones and allenes are known to facilitate the rapid synthesis of several indole derivatives. The chemoselectivity of these complicated transformations can be influenced by substrate functionalization, reaction conditions, and catalyst control. While seminal studies established primary reactivity patterns, recent work has illustrated the impact of these cascade reactions for creating diverse libraries, increased the breadth of these methods with facilitated access to challenging nitrones, and shown that these transformations can be controlled by asymmetric catalysis.

Synthesis and Transformations of Nitrones for Organic Synthesis

“…These formation of indoles have been extended to prepare dihydrocarbazole or dihydropyridoindole products. 238,239 Anderson and co-workers discovered the first catalytic asymmetric version of these cascade reactions providing dihydropyrido[1,2a]indoles with high diastereoselection and excellent enantioselectivity (eq 101). 240 The reaction of N-aryl-α,β-unsaturated nitrones with electron-deficient allenes in the presence of phosphoric acid catalyst gives 3-functionalized indoles.…”

“…These formation of indoles have been extended to prepare dihydrocarbazole or dihydropyridoindole products. , Anderson and co-workers discovered the first catalytic asymmetric version of these cascade reactions providing dihydropyrido­[1,2- a ]­indoles with high diastereoselection and excellent enantioselectivity (eq ). …”

Regio‐ and Enantioselective (3+3) Cycloaddition of Nitrones with 2‐Indolylmethanols Enabled by Cooperative Organocatalysis

“…Nitrones are basic materials and important intermediates in organic synthesis that have attracted intense attention from the chemistry community. [1] In particular, nitrones can act as three-atom building blocks in catalytic asymmetric (3 + n) cycloadditions,p roviding au seful tool for the synthesis of enantioenriched heterocyclic compounds (Scheme 1). [2][3][4][5][6][7][8][9] Nitrones are suitable 1,3-dipoles for constructing optically pure five-membered isoxazolidine frameworks via catalytic asymmetric (3+ +2) cycloadditions (Scheme 1a).…”

Nickel(II)-Catalyzed [3 + 2] Cycloaddition of Nitrones and Allenoates to Access N-Vinylindoles and N-Vinylpyrroles

“…In the last two decades, α,β-unsaturated nitrones have attracted great attention in the preparation of complex target molecules owing to the rich transformations of the α,β-unsaturated bonds in nitrones during their reaction with other dipolarphiles . In particular, the cycloaddition of α,β-unsaturated nitrones with allenoates was investigated . For example, in 1999, Ishar and coworkers developed the reaction of benzopyranone nitrone and allenoate to access benzoindolizines through a metal-free cascade of a [3 + 2] cycloaddition/[3,3]-rearrangement/retro-Mannich reaction/Diels–Alder reaction (Scheme A) .…”