Copper‐Catalyzed Cross‐Coupling Interrupted by an Opportunistic Smiles Rearrangement: An Efficient Domino Approach to Dibenzoxazepinones

Abstract

Unexpected Smiles! An unusual and highly regioselective synthesis of dibenzoxazepinones by a domino sequence assisted by an unexpected Smiles rearrangement is reported. The process is effective on electronically differentiated phenols and shows a high tolerance to variation in the benzamide substituents. A plausible path for the reaction, supported by preliminary mechanistic data, is offered.

An efficient cascade approach to dibenzoxazepinones via nucleophilic aromatic substitution and Smiles rearrangement

“…2). 10 We herein wish to address another solution based on a cascade approach of nucleophilic aromatic substitution and Smiles rearrangement without involving any transition-metals. As an ongoing study in our group to the economical synthesis of heterocyclic systems, 11 we envisioned that swapping the halogen atoms on the benzamide motif would lower the activation energy so that it could allow to utilize the electronic diverse aromatic reactants (Eq.…”

“…Furthermore, the iodide or bromide substrates may require an copper-involved Ullmann protocol to assist the initial nucleophilic addition step. 10,12 To explore the scope of substituents on both the benzamide and phenol parts, various substrates 1 and 2 were exposed to the optimized reaction condition ( Table 2). The position of substituents on the benzamide was tolerated in the cascade reaction and gave similar yields (3c-d), however, sluggish reactivity was found when varying the electronical property on benzamides (3b,e-h).…”

“…13 All the reactions examined gave exclusive Smile rearrangement products and the direct cyclized Goldberg regiomer was not found under our conditions. 10,14 For example, NOESY spectra of representative compounds 3a, 3g, and 3t displayed the cross peaks between the N-substituent groups and the neighbor phenyl singlet protons; while compound 3m showed the cross peak between the N-methyl group and the neighbor phenyl doublet proton.…”

Stereoselective Access to 1-[2-Bromo(het)aryloxy]propan-2-amines Using Transaminases and Lipases; Development of a Chemoenzymatic Strategy Toward a Levofloxacin Precursor

“…9 Substrates 1a-g were alkylated using an equimolecular amount of chloroacetone (2) in the presence of 2 equiv of potassium carbonate and catalytic amounts of potassium iodide in refluxing acetone, obtaining after 2 h the ketones 3a-g in high to quantitative yields. Prochiral ketones 3a-g served as substrates for biotransamination reactions, but also as starting materials for the synthesis of the racemic amines through reductive amination using 2 equiv of sodium cyanoborohydride in combination with a large of excess of ammonium acetate in methanol.…”

“…23 The synthetic pathway is depicted in Scheme 4 starting from the commercially available 2,3-difluorophenol (9). First, a selective bromination of the aromatic ring was performed using 2 equiv.…”