Bifunctional Brønsted Base Catalyzed Mannich Reaction of β‐Alkoxy α‐Keto Amides: Stereocontrolled Entry to Functionalized Amino Diols

Abstract

The potential of β-alkoxy α-keto amides as pronucleophiles in the enantioselective Mannich type reaction with p-nosyl imines is presented. The proper combination of β-alkoxy α-keto amides and a squaramide-based Brønsted base catalyst produced highly enantioenriched Mannich adducts, which may be transformed into functionalized amino diols.

Recent Advances in Squaramide‐Catalyzed Asymmetric Mannich Reactions

“…In order to explore its practical value, the gram-scale reaction was performed and the corresponding product was obtained with yield and diastereoselectivity decreased slightly (86% yield, 16:1 dr) and the enantioselectivity did not change (89% ee). An asymmetric Mannich reaction of α-keto amides 119 to different N-protected imines 118 catalyzed by squaramide catalyst C16 was developed in 2018 [71] (Scheme 49). The Mannich products 120 smoothly transformed into amino diols through reduction step, and the final compounds 121 were obtained in moderate yields (45-68%) with good to excellent diastereoselectivities (70:30-99:1 dr) and moderate to excellent enantioselectivities (58-96% ee).…”

“…An asymmetric Mannich reaction of α‐keto amides 119 to different N ‐protected imines 118 catalyzed by squaramide catalyst C16 was developed in 2018 [71] (Scheme 49). The Mannich products 120 smoothly transformed into amino diols through reduction step, and the final compounds 121 were obtained in moderate yields (45–68%) with good to excellent diastereoselectivities (70:30–99:1 dr) and moderate to excellent enantioselectivities (58–96% ee).…”