The first synthesis of benzo[e]cycloalk[g]oxazocinone atropisomers via lactonization of N-mesyl- or N-arylsulfonyl-N-[2-(1-cycloalken-1-yl)-6-methylphenyl]glycines

The article describes an efficient access to cycloalkene-annulated benzoxazocines displaying both axial and central chiralities, via a domino halogenation-lactonization reaction of substituted glycine precursors. Upon interaction between N-[2-(1-cyclohexen-1-yl)-6-methylphenyl]-N-mesyl- or -N-arylsulfonylglycines and bromine an axially chiral mixture of (aR,R)- and (aS,S)-enantiomers of heterocycles with benzo[e]cyclohexa[g][1,4]oxazocine core is formed as the main reaction product, which slowly transforms into the corresponding mixture of (aS,R)- and (aR,S)-enantiomers. The reaction of N-tosyl analog of these glycines with iodine under the same conditions leads to the heterocycle of spiro[4,1-benzoxazepin-5,1'-cyclohexane] structure. Upon treatment of the cyclopentenyl homologue N-tosylate of these glycines with molecular bromine or iodine, in both cases, a compound with the benzoxazocinone backbone is obtained as the only reaction product. (C) 2021 Elsevier Ltd. All rights reserved.