Functionalization of inert C–H bonds has received tremendous attention due to the inherent atom economy and efficiency of the transformations of the starting materials. As compared to transition-metal-catalysed C–H activation, organocatalysis is much less commonly applied for direct functionalization of inert C–H bonds. The α C(sp³)–H bonds of NH₂-unprotected benzylamines usually are inert in most reactions due to the extremely low Brønsted acidity. Here we utilize a chiral pyridoxal bearing a quaramide side chain as a bifunctional carbonyl catalyst to activate the α C(sp³)–H bond of NH₂-unprotected benzylamines, making it acidic enough to be deprotonated under mild conditions. Based on the carbonyl catalysis strategy, we develop a direct asymmetric α C–H addition of benzylamines to aldehydes, providing one of the most straightforward methods for the synthesis of chiral β-aminoalcohols with excellent diastereo- and enantioselectivities.

由于起始材料的固有原子经济性和转化效率，惰性 C-H 键的功能化受到了极大的关注。与过渡金属催化的 C-H 活化相比，有机催化不太常用于惰性 C-H 键的直接功能化。由于极低的布朗斯特酸度，NH ₂ -未保护的苄胺的 α C( sp ³ )–H 键通常在大多数反应中呈惰性。在这里，我们利用带有 quaramide 侧链的手性吡哆醛作为双功能羰基催化剂来激活NH _{2的 α C(} sp ³ )–H 键-未受保护的苄胺，使其酸性足以在温和条件下去质子化。基于羰基催化策略，我们开发了苄胺与醛的直接不对称 α C-H 加成反应，为合成具有出色非对映和对映选择性的手性 β-氨基醇提供了最直接的方法之一。