The regioselectivity of the addition of HO‐acids to the activated π bond in N,N‐bis(oxy)enamines has been found to be dramatically dependent upon the solvent. Mechanistic investigations and quantum‐chemical calculations revealed that solvent affects the reaction pathway. In basic solvents (DMF, NMP, DMSO), N,N‐bis(oxy)enamines were converted into nitrosoalkenes by a Lewis base promoted process followed by oxy‐Michael addition of the HO‐acid. In non‐polar solvents (toluene, CH2Cl2), the reaction occurs by an acid‐promoted SN′ substitution of the N‐oxy‐group via a highly reactive N‐vinyl‐N‐alkoxynitrenium species. Based on these studies, general and efficient protocols for the oximinoalkylation of various HO‐acids (carboxylic acids, phenols, hydroxamic, phosphoric and sulfonic acids) employing readily available N,N‐bis(oxy)enamines were developed. These methods proved to be applicable to the post‐modification of natural molecules bearing acidic OH groups (such as steroidal hormones, bile acids, protected amino acids and peptides) and ligands (BINOL). The resulting α‐oxyoximes were demonstrated to be useful precursors of valuable 1,2‐amino alcohol or 1,2‐hydroxylamino alcohol derivatives, including the antiarrhythmic drug Mexiletine and a potent matrix metalloproteinase inhibitor.

An approach to the synthesis of α‐halo oxime ethers from readily accessible nitronates and nitro compounds via bis(oxy)enamines is reported. A key step of the strategy involves the unprecedented reaction of bis(oxy)enamines with a metal (Co, Zn, Mg, Mn) halide that acts as both a promoter and halide (Br, I, Cl) source. A variety of cyclic and acyclic ethers of α‐halo oximes, including previously unavailable trimethylsilyl ethers of α‐iodo oximes, have been synthesized in good‐to‐high yields.

The synthesis of α-nitroxy-substituted oxime derivatives has been achieved by an unprecedented metal-assisted addition of a nitrate anion to bis(oxy)enamines, which are readily available from nitronates or nitroalkanes. The method has a broad scope and provides access to α-nitroxy-oximes and their cyclic ethers including nitroxy-substituted isoxazolines and dihydro-1,2-oxazines, which are of interest as potential NO-donors and intermediates in the synthesis of bioactive molecules.

A general approach to various α-phosphorussubstituted oximes (β-oximinoalkyl-substituted phosphonates, phosphine oxides, phosphine−borane complexes, and phosphonium salts) was developed. The strategy exploits hitherto unknown Michael addition of PH-containing compounds (diphenylphosphine oxide, diisopropyl phosphite, phosphine− borane complexes, and triphenylphosphonium bromide) to unstable conjugated nitrosoalkenes, which are generated in situ from corresponding nitrosoacetals. The resulting α-phosphorus-substituted oximes can be considered as useful P-, N-, and O-ligands for catalysis and precursors to valuable βaminophosphonates.

The method offers access to various cyclic and acyclic α‐nitroxy‐oxime derivatives which are obtained starting from bis(oxy)enamines which may be prepared in situ.