N,O-acetals are part of many synthetic intermediates and important skeletons of numerous natural products and pharmaceutical drugs. The most straightforward method of the synthesis of N,O-acetals is the enantioselective addition of O-nucleophiles to imines. However, using this method for the synthesis of linear chiral N,O-ketals still remains challenging due to the instability of raw materials under acidic or basic conditions. Herein, we developed a Cu-catalyzed asymmetric addition of alcohols to β,γ-alkynyl-α-imino esters under mild conditions, providing the corresponding linear chiral N,O-ketals with up to 96% ee. The method tolerates some variation in the β,γ-alkynyl-α-imino ester and alcohol scope, including some glucose and natural amino acid derivatives. Computational results indicate that the Boc group of the substrates assist in the extraction of hydrogen atoms from the alcohols to promote the addition reactions. These products could be synthesized on a gram-scale and can be used in several transformations. This asymmetric addition system provides an efficient, mild, gram-scale, and transition-metal-catalyzed synthesis of linear chiral N,O-ketals.

N , O-缩醛是许多合成中间体的一部分，也是许多天然产物和药物的重要骨架。最直接的N , O-缩醛合成方法是将O-亲核试剂与亚胺进行对映选择性加成。然而，由于原料在酸性或碱性条件下的不稳定性，使用这种方法合成线性手性N，O-缩酮仍然具有挑战性。在此，我们开发了一种 Cu 催化的醇不对称加成到β , γ -炔基- α -亚氨基酯在温和条件下，提供相应的线性手性N，O-缩酮， ee高达 96% 。该方法容许β、γ-炔基-α-亚氨基酯和醇范围的一些变化，包括一些葡萄糖和天然氨基酸衍生物。计算结果表明，底物的 Boc 基团有助于从醇中提取氢原子以促进加成反应。这些产品可以在克级合成，并且可以用于多种转化。这种不对称加成系统提供了一种高效、温和、克级和过渡金属催化的线性手性N , O -缩酮合成。