Copper‐Catalyzed Aqueous N−O Bond Cleavage of 2‐Oxa‐3‐Azabicyclo Compounds to Cyclic cis‐1,4‐Amino Alcohols

The N−O bond cleavage of 2‐oxa‐3‐azabicyclo substrates, which are readily prepared by the hetero Diels‐Alder reaction between nitroso dienophiles and cyclic 1,3‐dienes, was effectively catalyzed by heterogeneous copper‐on‐carbon (Cu/C) under aqueous conditions to give the corresponding cyclic cis‐1,4‐amino alcohol derivatives. The present method was applied to the direct incorporation of the hydroxy and amino groups derived from a nitroso substrate into cyclic 1,3‐dienes with cis‐selectivity by the combination of the in situ formation of 2‐oxa‐3‐azabicyclo compounds and following Cu/C‐catalyzed N−O bond cleavage. The obtained cis‐4‐aminocyclohexenols, derived from cyclohexadiene as a cyclic 1,3‐diene, could be selectively oxidized by using the ruthenium‐on‐carbon (Ru/C) catalyst under oxygen atmosphere to the corresponding 4‐aminocyclohexenones at 50–65 °C or para‐iminoquinones at 100–110 °C as useful reactive synthetic precursors. Dr. NO vs. Dr. Cyclo: The N−O bond cleavage of 2‐oxa‐3‐azabicyclo compounds could proceed in the presence of catalytic Cu/C under aqueous conditions to give the cyclic cis‐1,4‐amino alcohol derivatives. Furthermore, the direct incorporation of amino and hydroxyl groups to cyclic 1,3‐dienes could also be accomplished via the hetero Diels‐Alder reaction with nitroso dienophiles and cyclic 1,3‐dienes and the following Cu/C‐catalyzed N−O bond cleavage in a one‐pot manner.