Catalytic Asymmetric Approach to 1,3,4,5-Tetrahydro-1,4-benzodiazepin-2-ones in One-Pot

Herein we illustrate a first asymmetric synthesis of medicinally attractive tetrahydro-1,4-benzodiazepin-2-ones performed under catalytic conditions and one-pot fashion. The process relies on a sequential Knoevenagel reaction/asymmetric epoxidation/domino ring-opening cyclization (DROC) using commercially available aldehydes, phenylsulfonylacetonitrile, cumyl hydroperoxide, 2-(aminomethyl)aniline and a readily available quinine-derived urea as the catalyst. The heterocycles have been isolated with good regioselectivity, satisfactory to good yield and up to 98 % ee. The protocol proved also to be suitable for the preparation of previously undescribed 1,5-dihydro-4,1-benzoxazepin-3(2H)-ones with up to 86 % ee.A first catalytic and asymmetric synthesis of medicinally relevant tetrahydro-1,4-benzodiazepin-2-ones and unprecedented 1,5-dihydro-4,1-benzoxazepin-3(2H)-ones, has been developed. The telescoped approach relies on the use of commercially available reagents, recyclable organocatalyst and a single solvent. The heterocycles were isolated in good overall yield (30-69 %) and satisfactory to high enantioselectivity (up to 98 % ee). image