Cyclization of Imides to 2-Azabicycles via Aminoketyl Radicals by Using Samarium(II) Iodide–Water: Reaction Development, Synthetic Scope, and Mechanistic Studies

Shicheng Shi; Roger Lalancette; Michal Szostak

doi:10.1055/s-0035-1560437

Synthesis, Table of Contents

Synthesis 2016; 48(12): 1825-1854
DOI: 10.1055/s-0035-1560437

special topic

Cyclization of Imides to 2-Azabicycles via Aminoketyl Radicals by Using Samarium(II) Iodide–Water: Reaction Development, Synthetic Scope, and Mechanistic Studies

Authors

Shicheng Shi

Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, USA Email: michal.szostak@rutgers.edu
Roger Lalancette ◊

Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, USA Email: michal.szostak@rutgers.edu
Michal Szostak*

Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, USA Email: michal.szostak@rutgers.edu

Abstract

All articles of this category

^◊ To whom correspondence about crystallographic data should be addressed

Dedicated to Professor Henri Kagan

Abstract

The first highly selective method for direct addition of aminoketyl radicals [R–C^•(O^–)NR¹R²], generated from five- or six-membered cyclic imides, to nonactivated π-systems by using the SmI₂–H₂O reagent is reported. The transformation is operationally simple, scalable, and provides access to valuable angular 2-azabicycles containing three contiguous stereocenters with excellent diastereoselectivity (>95:5 dr). The protocol accommodates a wide range of π-acceptors that can be modulated by the alcohol additive used. Notably, the transformation provides the first general method for generation of aminoketyl radicals by a direct electron capture to amide bonds, thus opening new vistas for applications of these underutilized intermediates in a diverse array of open-shell reaction pathways. Systematic studies on the effects of additives, the scope and limitations of the reaction, and the reaction mechanism are reported.

Key words

azabicycles - samarium diiodide - reductive coupling - aminoketyl radicals - stereoselectivity - cyclizations - umpolung

Full Text

References

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57 Crystallographic data for compounds 8 and 54 have been deposited with the accession numbers CCDC 1449857 and 1449896, respectively, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.
58 Roughley SD, Jordan A. J. Med. Chem. 2011; 54: 3451

59a Imamoto T, Ono M. Chem. Lett. 1987; 501
59b Dahlén A, Hilmersson G. Eur. J. Inorg. Chem. 2004; 3020
59c Szostak M, Spain M, Procter DJ. J. Org. Chem. 2012; 77: 3049

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