Twisting the ethano-Tröger's base: the bisamide

Abstract

The typically planar amide when incorporated into bicyclic systems can undergo a significant distortion from planarity resulting in physical properties and reactivity that deviate from classical amide behaviour. Herein, we report a succinct protocol that utilises potassium permanganate to selectively α-oxygenate the benzylic position of ethano-Tröger's base derivatives to yield a new class of twisted bisamides. Additionally, we report the first synthesis of an ethano-Tröger's base derivative bearing substituents in the positions ortho to the nitrogen atoms.

Twisted Amides: From Obscurity to Broadly Useful Transition‐Metal‐Catalyzed Reactions by N−C Amide Bond Activation

“…Accounts on the amide bond N–C cross‐coupling have been published ,. Moreover, the synthesis of ethano‐‐Tröger′s base twisted bisamides has been developed …”

Chemistry of Bridged Lactams: Recent Developments

“…In 2017, Gouverneur, Cvengros and co-workers reported the synthesis of ethano Tröger’s base twisted bis-amides (Figure 13) [34]. Their approach involves one-step oxidation of the ethano-Tröger’s base precursors under the conditions reported earlier by Wärnmark (Figure 13, box) [35].…”

Tröger’s Base Twisted Amides: High Amide Bond Twist and N-/O-Protonation Aptitude

“…Stimulated by our interest in the properties of nonplanar cyclic and acyclic amides, we were attracted by the recently reported examples of Tröger’s base twisted amides , as models for a substantial twist of the amide bond. In 2012, Wärnmark and co-workers demonstrated that direct oxidation of the venerable Tröger’s base scaffold can be used to afford a twisted bis-amide with a remarkable twist of the amide bond (Figure B, τ = 41.0°, χ N = 57.9°, N–C­(O) = 1.430 Å, CO = 1.210 Å).…”

“…In 2012, Wärnmark and co-workers demonstrated that direct oxidation of the venerable Tröger’s base scaffold can be used to afford a twisted bis-amide with a remarkable twist of the amide bond (Figure B, τ = 41.0°, χ N = 57.9°, N–C­(O) = 1.430 Å, CO = 1.210 Å). In 2017, Cvengroš and co-workers reported the synthesis of an extended Tröger’s base twisted amide using one-step oxidation of the ethano-Tröger’s base (Figure B, τ = 29.8°, χ N = 45.5°, N–C­(O) = 1.401 Å, CO = 1.215 Å). Since the Tröger’s base twisted amides reported by Wärnmark and Cvengroš (1) represent rare examples of significantly twisted amides with the additive Winkler–Dunitz parameter approaching 100° ((τ + χ N ) = 98.9° and 75.3°, respectively) and, in addition, (2) are prepared by a more facile and faster approach , that related twisted amides, ,, a better understanding of the structures and energetics could facilitate the design of novel twisted amides of both theoretical and practical synthetic interest. − ,− In this manuscript, we report a computational investigation into the structures and proton affinities of a diverse set of Tröger’s base twisted amides and compare them with related nonplanar bridged lactams.…”