Synthesis of Indolizines and Benzoindolizines by Annulation of Donor‐Acceptor Cyclopropanes with Electron‐Deficient Pyridines and Quinolines

Abstract

The formal [3+2] dipolar cycloaddition (or annulation) of donor‐acceptor cyclopropanoate esters with pyridines and 5‐nitroquinoline is reported. Electron‐deficient pyridine dipolarophiles (R=CN, CO2Et, COMe) participate in the annulation whereas electron rich species do not. The product 2,3‐dihydroindolizines undergo rapid autooxidation, and the X‐ray structures for two of the aromatic products are reported.

Ein neues goldenes Zeitalter in der Chemie Donor‐Akzeptor‐substituierter Cyclopropane

“…2). [57] Eine [3+2]-Cycloaddition dieser Art wurde bereits in der Totalsynthese des Alkaloids FR901483 genutzt, um im Schlüsselschritt das oligocyclische Grundgerüst aufzubauen. Entscheidenden Einfluss hatte hierbei die Reihenfolge der Reagentienzugabe.…”

“…Außer Pyridinen konnten auch elektronenarme Chinoline in entsprechenden Reaktionen für die Synthese von Benzoindolizinen eingesetzt werden. [57] Eine [3+2]-Cycloaddition dieser Art wurde bereits in der Totalsynthese des Alkaloids FR901483 genutzt, um im…”

C-2/C-3 Annulation and C-2 Alkylation of Indoles with 2-Alkoxycyclopropanoate Esters

“…15 In this regard, it has been reported by Kerr and co-workers that the annulation of indoles with 1,3-dipoles is a successful strategy for rapidly increasing the molecular complexity by simultaneous functionalization of C-2 and C-3, although yields for the annulation products are generally modest. 16 This was of particular interest to us as we have been developing methods for hetereocycle synthesis based on the annulation of the related family of 2-alkoxycyclopropanoate esters with nitriles, 17 pyridines 18 and other reaction partners. 19 We envisioned that the more nucleophilic nature of the zwitterionic intermediates from these donor-acceptor cyclopropanes (i.e., an ester versus a malonate) may also undergo annulation with indoles, and in this report we describe our progress in indole annulation and C-2 alkylations.…”

Synthesis and Reactivity of Bicyclo[3.2.1]octanoid-Derived Cyclopropanes

“…For example, donor-acceptor cyclopropanes may undergo ionization and further reaction upon treatment with TMSOTf. 13,14,15 Thus, we treated cyclopropane 2 with TMSOTf in acetonitrile which afforded polycyclic imine 39 in moderate yield (51%), presumably through a dipole intermediate such as 38 (Table 1, entry 1).…”