Synthesis 2016; 48(19): 3254-3262
DOI: 10.1055/s-0035-1562467
paper
© Georg Thieme Verlag Stuttgart · New York

Configurationally Stable Doubly Bridged Biphenyl Azocines through Copper-Catalyzed Double Carbene Insertions into the Corresponding Azepines

Steven Harthong
a   University of Geneva, Department of Organic Chemistry, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland
,
Elodie Brun
a   University of Geneva, Department of Organic Chemistry, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland
,
Stéphane Grass
a   University of Geneva, Department of Organic Chemistry, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland
,
Céline Besnard
b   University of Geneva, Laboratory of Crystallography, Quai Ernest Ansermet 24, 1211 Geneva 4, Switzerland
,
Thomas Bürgi
c   University of Geneva, Department of Physical Chemistry, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland   Email: jerome.lacour@unige.ch
,
Jérôme Lacour*
a   University of Geneva, Department of Organic Chemistry, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland
› Author Affiliations
Further Information

Publication History

Received: 03 June 2016

Accepted after revision: 22 June 2016

Publication Date:
03 August 2016 (online)


In memory of Jean-François Normant

Abstract

Doubly bridged biphenyl azocines can be prepared in a single step through copper-catalyzed reactions of a doubly bridged biphenyl azepine and diazodiester reagents. Double [1,2]-Stevens rearrangements occur at 100 °C to afford doubly tethered eight-membered rings (49 to 61%) as trans and cis regioisomers (1:1 ratio). These products present an axial chirality. ECD and VCD analyses of the separated enantiomers (CSP-HPLC) were used to assign the absolute configuration. High configurational stability is observed for both regioisomers as racemization does not occur after 1 week of heating at 208 °C in dodecane (ΔG > 41 kcal·mol–1). Interestingly, reactions performed at 40 °C retain a certain level of enantiospecificity (82–86%), avoiding, for the most part, thermal racemization of the starting material.

Supporting Information

 
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