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

Abstract

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.

Aqueous ZnCl2 Complex Catalyzed Prins Reaction of Silyl Glyoxylates: Access to Functionalized Tertiary α-Silyl Alcohols

“…To verify the transformations of Prins reaction products (Scheme ), [1,2]-Brook rearrangement of 3k was first carried out under PTC conditions, generating the corresponding product 4 in 75% yield. Moreover, the TBS group in 3k was efficiently removed on treatment with TBAF, and the corresponding product 5 was obtained in 90% yield.…”

“…1-Methylenecyclohexane ( 1al ) was purchased from commercial sources and directly used without further purification. Silyl glyoxylates 2a , 2e , and 2i – l have been prepared in our previous work, and silyl glyoxylates 2b – d and 2f – h were newly prepared according to the reported method . The NMR data of 2b – d and 2f – h were provided.…”

“…For example, with alkynes and Grignard reagents as the nucleophiles, the addition reaction of acylsilanes was well developed by the Marek, Chan, and Harutyunyan groups, affording the tertiary α-silyl alcohols in high yields. Moreover, with aldehydes, sulfur or other nucleophiles, tertiary α-silyl alcohols were obtained under mild conditions. More recently, the Oestreich group reported a new approach to the synthesis of functionalized tertiary α-silyl alcohols via a copper-catalyzed addition of acylsilanes with an in situ formed boron nucleophile across 1,3-diene.…”

“…Silyl glyoxylates are useful organosilicon reagents in the Brook rearrangement. , Due to the poor reactivity of the carbonyl group in silyl glyoxylates, the high nucleophilicity of metal-based reagents is used in the transformations. , Generally, Lewis acid activated aldehydes or acetals are typically used in Prins reactions, but silyl glyoxylate as an electrophile in the Prins reaction is still a limitation, and the undeveloped Prins reaction of silyl glyoxylates is highly desirable owing to the low reactivities of the unusual carbonyl groups in silyl glyoxylates, although an electron-withdrawing group is directly bonded to the sp 2 -carbon atoms . It is well-known that Lewis acid catalysts lower the activation barriers of enophiles, and our previous work indicated that the carbonyl groups in silyl glyoxylates could also be activated by Brønsted acids, hydrogen bonding, and water. , The classic Lewis acids, such as TiCl 4 , FeCl 3 , and AlCl 3 , have been used in the Prins reaction (Scheme a) . However, they exhibited poor reactivities in the Prins reaction of silyl glyoxylates (Table for details).…”

“…However, they exhibited poor reactivities in the Prins reaction of silyl glyoxylates (Table for details). Meanwhile, our preliminary studies ,,, indicated that the proposed activation models via hydrogen bonding failed in the Prins reaction of silyl glyoxylates (Table for details). It is essential to develop a highly efficient catalyst to activate the carbonyl groups in silyl glyoxylates.…”