Asymmetric Hydrative Aldol Reaction (HAR) via Vinyl‐Gold Promoted Intermolecular Ynamide Addition to Aldehydes

• Published in: Angewandte Chemie Vol. 135; no. 31
• Main Authors: Yuan, Teng, Radefeld, Kelton, Shan, Chuan, Wegner, Carter, Nichols, Erin, Ye, Xiaohan, Tang, Qi, Wojtas, Lukasz, Shi, Xiaodong
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.08.2023
• Subjects: Aldehydes; Alkynes; Amides; Asymmetric Catalysis; Asymmetry; Catalysts; Chemistry; Functional groups; Gold; Gold Catalysis; Nucleophiles; Stereoselective Hydrative Aldol Reaction; Stereoselectivity; Vinyl Gold; Ynamide
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202305810

Herein, we reported an intermolecular asymmetric hydrative aldol reaction through vinyl‐gold intermediate under ambient conditions. This tandem alkyne hydration and sequential nucleophilic addition afforded a “base‐free” approach to β‐hydroxy amides with high efficiency (up to 95 % yields, >50 examples). Vinyl gold intermediate was applied as reactive nucleophile and Fe(acac)3 was used as the critical co‐catalyst to prevent undesired protodeauration, allowing this transformation to proceed under mild conditions with good functional group tolerance and excellent stereoselectivity (>20 : 1 d.r. and up to 99 % ee). The application of Fe(acac)3 as a cocatalyst prevents vinyl gold protodeauration, allowing for its nucleophilic addition to aldehydes. Hence, the intermolecular vinyl gold‐promoted asymmetric hydrative aldol reaction (HAR) of ynamides and aldehydes was shown possible and is herein presented. The reaction leads to β‐hydroxy amides with high yields (up to 95 %) and stereoselectivity (up to >20 : 1 d.r, 99 % ee) under mild conditions (base‐free, 40 °C).