Chiral Synthesis of McGeachin-Type Bisaminals

Abstract

Bridged [3.3.1]-bisaminal structures, namely 6,12-epiminodibenzo­[b,f]­[1,5]­diazocines, are herein named McGeachin-type bisaminals. The TsOH-catalyzed chiral synthesis of McGeachin-type bisaminals is first developed by condensation of two molecules of 2-(methylamino)­benzaldehyde and one molecule of chiral amines. Two chiral diastereomers are generated simultaneously and are isolated by column chromatography in a total yield of up to 99%. The absolute structure of one stereoisomer was determined by X-ray crystallography.

Synthetic strategies and diversification of dibenzo[1,5]diazocines

“…The amine-iminium addition followed by the deprotonation gives the final products (Scheme 27). 62 The crystal structure determination of 55, 62 Scheme 27, revealed a close resemblance, at least in terms of the bridging of the dibenzodiazocine ring by the amine-N atom, to that noted above for 38b.…”

“…From a literature survey, it is apparent there are several groups working on synthetic methodologies for the preparation of these derivatives. However, it was found that most of the articles ignored the specific characterisation of both stereocentres and racemic configurations of the products, 62 which is probably due to the difficulty in product isolation. In 2000, Frank et al 63 reported two examples of epiminodibenzo [1,5]diazocines.…”

“…The formation of 54 is suggested to arise from the amination of terminal hydroxyl 53 with an amino substrate. 76 The chiral synthesis of diazocine-based McGeachin-type bisaminals was first reported by Chen et al 62 in 2020 from the reaction of 2-(methylamino)benzaldehyde with various substituted chiral amines. The optimisation of the reaction conditions was carried out by varying acid or metal catalysts, solvents and temperatures.…”

Base-Catalyzed, Solvent-Free Synthesis of Rigid V-Shaped Epoxydibenzo[b,f][1,5]diazocines

“…The long-standing interest in Tröger’s base (A) has recently culminated in the efficient synthesis of its heteroatom analogues, epiminodibenzodiazocines, bearing a nitrogen bridge (structure B in Scheme ). In contrast, to the best of our knowledge, no efficient synthetic approach to diazocines, bearing an oxygen bridge, has been developed so far (structure C in Scheme ). We anticipated that the missing link should be easily provided by the autocondensation of o -aminophenones, providing a new scaffold for supramolecular chemistry.…”

Epoxydibenzo[b,f][1,5]diazocines: From a Hidden Structural Motif to an Efficient Solvent-Free Synthetic Protocol

“…9 It should be noted that more structurally complex molecules could be classified as McGeachin-type bisaminals, arising from competitive polycondensation of aminobenzaldehyde derivatives (trimeric C and tetrameric D, Scheme 1). Recent improvements in the synthetic protocol by Aubé, 10 Wang, 11 Sridharan, 12 and Xu and Yang 13 have delivered an easy access to large quantities of these unique molecules.…”