C₂-Symmetric Chiral Bisoxazolines as Hydrogen-Bond-Acceptor Catalysts in Enantioselective Aldol Reaction of β-Carbonyl Acids with Trifluoroacetaldehyde Hemiacetals

Abstract

A simple C-symmetric chiral bisoxazoline is demonstrated to use hydrogen bonding to catalyze an important family of aldol reactions of trifluoroacetaldehyde hemiacetals with various β-carbonyl acids. This reaction is highly enantioselective, delivering chiral nonracemic trifluoromethylated alcohols with excellent optical purity and good isolated yields. This concept of relaying chiral information via a chiral hydrogen-bond acceptor should be applicable to a vast number of organocatalytic processes.

Сhiral and Racemic Fields Concept for Understanding of the Homochirality Origin, Asymmetric Catalysis, Chiral Superstructure Formation from Achiral Molecules, and B-Z DNA Conformational Transition

“…Therefore, they are similar in terms of the structure and symmetry of both 1 and 2 favoured or disfavoured 1 and 2 key intermediates (C 2 symmetry of 33 and C 1 symmetry of key intermediates). A similar loss of C2 symmetry of an organocatalyst was observed at the key intermediate stage in the aldol reaction (18) of β-carbonyl acids with trifluoroacetalaldehyde over the C2-symmetric bisoxazoline catalyst [151] and analogou reactions [151][152][153][154][155][156]. A similar loss of C 2 symmetry of an organocatalyst was observed at the key intermediate stage in the aldol reaction (18) of β-carbonyl acids with trifluoroacetalaldehyde over the C 2 -symmetric bisoxazoline catalyst [151] and analogou reactions [151][152][153][154][155][156].…”

Catalytic Enantioselective Decarboxylative Aldol Reactions of Malonic Acid Half Thio(oxy)ester and β‐Ketoacids

“…In 2016, the same group first demonstrated the use of chiral bis(oxazoline) as H-bond-acceptor catalysts in asymmetric decarboxylative aldol reactions of β-keto acids 23 with trifluoroacetaldehyde hemiacetals 28 (Scheme 17). [18] The desired decarboxylative trifluoromethylated aldol products 29 were Scheme 13. Organocatalyzed enantioselective decarboxylative aldol reaction between β-ketoacids and isatin.…”

“…In 2016, the same group first demonstrated the use of chiral bis(oxazoline) as H‐bond‐acceptor catalysts in asymmetric decarboxylative aldol reactions of β‐keto acids 23 with trifluoroacetaldehyde hemiacetals 28 (Scheme 17). [18] The desired decarboxylative trifluoromethylated aldol products 29 were obtained in good to excellent yields (63‐98 %) and enantioselectivities (80‐95 % ee) in the presence of 5 mol% of chiral bis(oxazoline) K (Scheme 17). The application scope of this method with regards to different β‐keto acids 23 is broad and different (hetero)‐aryl substituents, aliphatic substituents, a β‐ionone‐derived β‐keto acid and even less reactive MAHO were well‐tolerated.…”

β‐Ketoesters as Mono‐ or Bisnucleophiles: A Concise Enantioselective Total Synthesis of (−)‐Englerin A and B

“…The groups of Ma and List/Song have developed interesting organocatalytic decarboxylative aldol reactions by using chiral bis(oxazoline) or cinchona‐type catalysts . However, in the former reaction, the β‐ketoester was reacted with highly reactive trifluoroacetaldehyde hemiacetals, and in the latter case, only malonic acid half‐thioesters were used as enolate surrogates . Initial screening experiments indicated these catalysts to be active; however, the products were isolated in low enantiopurity.…”