50314-82-4Relevant academic research and scientific papers
Addition of HO-Acids to N,N-Bis(oxy)enamines: Mechanism, Scope and Application to the Synthesis of Pharmaceuticals
Naumovich, Yana A.,Golovanov, Ivan S.,Sukhorukov, Alexey Yu.,Ioffe, Sema L.
, p. 6209 - 6227 (2017/11/15)
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.
The first catalytic inverse-electron demand hetero-Diels-Alder reaction of nitroso alkenes using pyrrolidine as an organocatalyst
Wabnitz, Tobias C.,Saaby, Steen,Jorgensen, Karl Anker
, p. 828 - 834 (2007/10/03)
The first catalytic inverse-electron demand hetero-Diels-Alder reaction of nitroso alkenes has been developed. Nitroso alkenes were generated in situ from α-halooximes and underwent [4 + 2]-cycloadditions with enamines as dienophiles formed from aldehydes and pyrrolidine (10 mol%) as an organocatalyst, The presence of a suitable heterogeneous buffer system was found to be essential and best results were obtained with sodium acetate trihydrate. The resulting 5,6-dihydro-4H-oxazines were obtained in moderate to good yields under mild reaction conditions. A catalytic cycle has been proposed and evidence for the cycloaddition mechanism has been obtained. Moderate asymmetric induction (42% ee) was observed when a chiral secondary amine was used.
