Chiral Phosphoric Acid Catalyzed Diastereo- and Enantioselective Mannich-Type Reaction between Enamides and Thiazolones

Abstract

An enantioselective Mannich-type reaction between enamides, serving as aliphatic imine equivalents, and thiazolones or an azlactone, serving as α-amino acid derived pronucleophiles, was investigated using a chiral phosphoric acid catalyst. By using thiazolones, Mannich adducts with a tetrasubstituted chiral carbon center at the α-position and an aliphatic substituent at the β-position were efficiently obtained with high diastereo- and enantioselectivities.

Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity

“…If the Z configuration is energetically inaccessible the reaction proceeds via a Type I  E pathway, the correct catalyst has large proximal and medium AREA(θ) 10, 11, 12, 13c, 14b, 19, 20, 21, 22, 40, 41, 42, 43, 44, 45, 46, 47. However, reactions involving displaced nucleophiles the best choice of catalyst has large proximal and small AREA(θ) 5, 8, 9, 30, 31, 48, 49, 50, 51, 52, 53. Higher enantioselectivities with small proximal bulk catalysts are not uncommon with displaced nucleophiles.…”

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 ]…”

“…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.…”

Recent Advances in Catalytic Asymmetric Reactions of Thiazolones, Rhodanines and Their Derivatives

“…The enantioselective Mannich-type reaction of 4Hthiazol-5-ones 7 and enamides 8 was disclosed by Momiyama and Terada et al via chiral phosphoric acid C3 catalyst (Scheme 4). [10] Notably, enamides 8 served as aliphatic imine equivalents to afford Mannich adducts 9 in 44-83% yields with 77-96% ee and 93:7-98:2 dr. The derivatization of adducts was also surveyed, furnishing α,β-diamino amide, α-tetrasubstituted α,β-diamino acid equivalents.…”