Organocatalyzed Direct Aldol Reaction of Silyl Glyoxylates for the Synthesis of α‑Hydroxysilanes

A novel organocatalyzed direct aldol reaction of aldehydes to silyl glyoxylates is disclosed. This method provides an efficient route to α-hydroxysilanes with excellent enantioselectivities (up to 99% ee) and high diastereoselectivities (up to >20:1 dr). In the new activation model of silyl glyoxylates, the hydrogen bond is critical to the reaction. A carbonyl group directly attached to silicon in acylsilanes could be activated by coordination to the proton of hydroxyl and carboxylic acid via a hydrogen bond. Moreover, commercially available cis-l-4-hydroxyproline is an ideal organocatalyst for activating both aldehydes and acylsilanes.

本研究报道了一种全新的醛与甲硅烷基乙醛酸酯（silyl glyoxylates）的有机催化直接羟醛缩合反应。该方法为合成α-羟基硅烷（α-hydroxysilanes）提供了高效途径，产物兼具优异的对映选择性（最高可达99% ee）与出色的非对映选择性（最高可达>20:1 dr）。在甲硅烷基乙醛酸酯的新型活化模型中，氢键对该反应至关重要：酰硅类化合物中直接与硅原子相连的羰基，可通过氢键与羟基、羧酸的质子配位实现活化。此外，市售的顺式-L-4-羟基脯氨酸是一种理想的有机催化剂，可同时活化醛与酰硅类化合物。