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

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.

Key words

azepine - azocine - carbenes - configurational stability - [1,2]-Stevens rearrangement - ylides

• References

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