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

Abstract

A novel method for the synthesis of epoxydibenzo[ b , f ][1,5]diazocines exhibiting a V-shaped molecular architecture is reported. The unique approach is based on unprecedented base-catalyzed, solvent-free autocondensation and cross-condensation of fluorinated o -aminophenones. The structure of the newly synthesized diazocines was confirmed independently by X-ray analysis and chiroptical methods. The rigidity of the diazocine scaffold allowed for the separation of the racemate into single enantiomers that proved to be thermally stable up to 140 °C. Furthermore, the inertness of the diazocine scaffold was demonstrated by performing a series of typical transformations, including transition metal-catalyzed reactions, proceeding without affecting the bis-hemiaminal subunit.

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

“…The reaction also exhibited a broad substrate scope and good tolerability with fluorinated 2-aminophenones, 66 featuring electron-donating and -withdrawing groups to create a series of 67 in up to 99% yield (Scheme 31). 82,83 The compounds are sufficiently stable to undergo the click and cross-metathesis reactions without ring opening of the diazocine scaffold.…”

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

“…The experimental and calculation details are provided. 14 In order to predict the OR sign and value at 589 nm, calculations were made for the same conformer as for ECD and VCD using four different levels of theory. The summary of calculations is presented in Figure 1 .…”

“…Taking into account the intriguing V-shaped structure of the fluorinated epoxydiazocines and the lack of a synthetic protocol for this class of compounds, we initiated further investigations to provide a practical, scalable protocol for their synthesis. 14 First, extensive optimization studies were conducted with respect to solvent and base (Scheme 13 ). It was found that o -aminophenone 39a undergoes self-condensation in many solvents, irrespective of their polarity or bonding character.…”

“…Herein, we wish to report an extensive review of synthetic efforts toward epoxydiazocines E and our recent findings on the synthesis of fluorinated epoxydibenzodiazocines via base-catalyzed solvent-free auto- and cross-condensation­ of fluorinated aminophenones. 14…”

Substrate Switchable Pathway for Selective Construction of Bridged Dibenzo[b,f][1,5]diazocines and Bridged Spiromethanodibenzo[b,e]azepines

“…Recently, epoxydibenzo [b,f] [ 1,5]diazocines were synthesized from fluorinated o-aminophenones. 14 In contrast, to the best of our knowledge, no efficient synthetic approach toward benzenodibenzo [b,f] [1,5]diazocine has been developed so far.…”