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.

Hydroquinone and benzoquinone-catalyzed aqueous Knoevenagel condensation.

A Knoevenagel condensation of various aldehydes with malononitrile effectively proceeded in the presence of hydroquinone/benzoquinone mixed catalysts at room temperature in H2O. Furthermore, γ-deuterium-labeled α,ß-unsaturated nitrile derivatives were also constructed via a deuteration of an aliphatic aldehyde in D2O using a basic resin and the subsequent Knoevenagel condensation.

Palladium on Carbon-Catalyzed Benzylic Methoxylation for Synthesis of Mixed Acetals and Orthoesters.

The palladium on carbon (Pd/C)-catalyzed direct methoxylation of the benzylic positions of linear benzyl and cyclic ether substrates proceeded in the presence of i-Pr2 NEt under an oxygen atmosphere to give the corresponding mixed acetals. Cyclic acetal derivatives could also be converted into orthoesters. The present direct methoxylation via a carbon-hydrogen (C-H) functionalization can be accomplished using the easily-removed Pd/C and molecular oxygen as a green oxidant. The obtained mixed acetals were transformed into the corresponding ether products by chemoselective substitution of the methoxy group using a silyltriflate, 2,4,6-collidine, and a nucleophile. The orthoester derivative could also be transformed into the cyclic ketal under similar reaction conditions.