Group-Assisted Purification Chemistry for Asymmetric Mannich-type Reaction of Chiral N-Phosphonyl Imines with Azlactones Leading to Syntheses of α-Quaternary α,β-Diamino Acid Derivatives

Abstract

An asymmetric Mannich-type reaction between chiral N-phosphonyl imines and azlactones [oxazol-5(4H)-ones] has been established under convenient conditions at room temperature. The reaction was performed without using any bases, additives, or catalysts to achieve up to excellent chemical yields and diastereoselectivity for 32 examples. The α-quaternary syn-α,β-diamino acid products were purified simply by washing the crude mixtures with cosolvents, following the group-assisted purification chemistry/technology, without involving traditional chromatography or recrystallization methods. The auxiliary can be readily removed and recycled for reuse. The absolute configuration was unambiguously assigned by X-ray structural analysis.

Multilayer 3D Chirality and Its Synthetic Assembly

“…This chirality belongs to a type of Multilayer Organic Framework (M-LOF) of single organic molecules with pseudo C 2 -chiral characteristics. The key element of this chirality is characterized by three layers of planes that are arranged nearly in parallel fashion with one on top and one below the planar center as presented in Figure 1 This discovery was resulted from our Group-Assisted Purification (GAP) chemistry by taking advantage of Nphosphonyl imine reagents and their usage for asymmetric reactions (Figure 2(a), a-c) [41][42][43][44][45][46][47]. In this project, we found that chiral and achiral N-phosphonyl-or N-phosphinyl groups avoided the formation of oily and sticky products; instead, they afforded special crystalline solids that can be purified simply by washing crude products with common petroleum solvents without the use of column chromatography and recrystallization.…”

Recent Progress in the Asymmetric Syntheses of α‐Heterofunctionalized (Masked) α‐ and β‐Amino Acid Derivatives

“…Given the variety of different catalysis protocols to achieve asymmetric Mannich type reactions, [ 69 ] this methodology is without doubt one of the most versatile strategies to access the α,β‐diamino acid scaffold from simple starting materials. [ 7,70–85 ]…”

“…Accordingly, it comes as no surprise that they have also been heavily utilized for asymmetric Mannich‐type approaches to access chiral α,β‐diamino acid derivatives (Scheme 33). [ 7,75–77 ] A powerful asymmetric procedure was published in 2011 by Toste's group, who applied the L18 (AuOBz) 2 complex to control the asymmetric reaction between azlactones 12 and aldimines 57 . [ 75b ] Shortly after, Hui and co‐workers utilized the chiral phosphate‐based Ag‐catalyst C30 to carry out these Mannich reactions with very high enantioselectivities as well.…”

“…Given the variety of different catalysis protocols to achieve asymmetric Mannich type reactions, [69] this methodology is without doubt one of the most versatile strategies to access the α, -diamino acid scaffold from simple starting materials. [7,[70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85] Cu-catalyzed Mannich reactions between α-amino-functionalized carbonyl derivatives and either aldimines or ketimines have been extensively explored by several groups over the course of the last decades (Scheme 30 and Scheme 31). [7,[70][71][72][73][74] In analogy to their elegant protocols to access α-halogenatedand α-oxygenated--AA derivatives via Mannich approaches (compare with Scheme 12 and Scheme 21), Shibasaki′s group developed a highly stereoselective anti-Mannich strategy to access α, -diamino acid derivatives as well.…”

“…Accordingly, it comes as no surprise that they have also been heavily utilized for asymmetric Mannich-type approaches to access chiral α, -diamino acid derivatives (Scheme 33). [7,[75][76][77] A powerful asymmetric procedure was published in 2011 by Toste′s group, who applied the L18(AuOBz) 2 complex to control the asymmetric reaction between azlactones 12 and aldimines 57.…”