含氮化合物高效高选择性合成方法学及其应用

酰胺是一类高度稳定、来源丰富的有机化合物。含氮化合物广泛存在于药物和农用化学品中。因而从酰胺合成胺有广泛需求。然而，酰胺选择性直接转化化学又是一个发展严重滞后的领域。近年来，经过包括申请人课题组在内的国内外诸多课题组的努力，酰胺直接转化正逐步形成一个新的研究前沿。然而，酰胺作为多用途的合成砌块，其研究总体仍处于起步阶段，许多具有挑战性，又有重要合成应用价值的转化亟待研究并取得突破。在本项目，我们从中选择15个重要转化加以研究，以期发展温和实用的酰胺直接转化及相关的含氮化合物高效高选择性合成方法。主要是:在温和条件下，叔酰胺和仲酰胺催化还原为胺的实用方法；叔酰胺催化还原为亚胺或醛；叔脂肪酰胺的催化偶联反应；酰胺作为醛的等效体的还原官能化：仲酰胺的还原双烷基化；仲酰胺和叔酰胺的还原催化不对称官能化。我们也将所发展的方法用于肽的选择性修饰和药物、生物碱的高效高选择性合成。

Amides are a class of highly stable and easily available organic compounds. N-Containing compounds are widespread among pharmaceuticals and agrochemicals. Thus the synthesis of amines from amides is in high demand. However, the direct and selective transformation of amides is under developed. In recent years, with the intensive efforts of several research groups including ours, this chemistry is emerging as a new frontier. Nevertheless, at the current early phase, many longstanding challenges yet important issues regarding the mild, direct and selective transformation of amides have not yet been resolved. We identified 15 of those problems as the targets of our current project in view of developing mild, selective, direct, and practical transformations of amides. Some other related methods for the synthesis of N-containing compounds will also be studied. The topics includes mild and practical catalytic reduction of both secondary and tertiary amides to amines; selective and catalytic partial reduction of tertiary amides to imines and aldehydes; Coupling of aliphatic tertiary amides to yield ketones, esters, alkenes; Coupling of aromatic tertiary amides to yield diaryl ketones, organoboron reagents; reductive bis alkylation of secondary amides; use of tertiary amides as surrogates of aldehydes in the Knoevenagel-type reactions; Asymmetric reductive functionalization of both secondary and tertiary amides to functionalized amines. The scope and value of our newly developed methods will be demonstrated in the selective modification of peptides, and by the concise and selective synthesis of medicines and natural products.