RESUMEN
The synthesis of unnatural α-amino acid derivatives has attracted considerable interest in recent years, as they are ubiquitous in protein synthesis and peptide-based drug discovery. Herein, we reported the chiral phosphoric acid catalyzed asymmetric reaction of indoles with ß,γ-alkynyl-α-imino esters for the enantioselective synthesis of unnatural indole-based α-amino acid derivatives. This asymmetric organocatalysis protocol enables efficient synthesis of unnatural α-amino acid derivatives with a tetrasubstituted stereogenic center and an alkyne moiety with up to 99% yield and 98% ee, resulting in operationally simple conditions, short reaction time, and broad substrate scope.
Asunto(s)
Aminoácidos , Indoles , Aminoácidos/química , Catálisis , Indoles/química , Ácidos Fosfóricos , EstereoisomerismoRESUMEN
In recent years, the synthesis of axially chiral compounds has received considerable attention due to their extensive application as biologically active compounds in medicinal chemistry and as chiral ligands in asymmetric catalysis. Chiral phosphoric acids are recognized as efficient organocatalysts for a variety of enantioselective transformations. In this review, we summarize the recent development of chiral phosphoric acid-catalyzed synthesis of a wide range of axially chiral biaryls, heterobiaryls, vinylarenes, N-arylamines, spiranes, and allenes with high efficiency and excellent stereoselectivity.
RESUMEN
Chiral allenes and styrenes are essential components in fields like medicinal chemistry, materials science, and organic synthesis. They serve a crucial role as chiral ligands and catalysts in asymmetric synthesis. Over the past decade, there has been a significant advancement in the development of practical methods utilizing organocatalytic strategies for the synthesis of chiral allenes and styrenes. It is noteworthy that despite extensive studies on the formation of allenes and styrenes, existing reviews on their construction confined to a specific organocatalysis, called chiral phosphoric acid catalysis, are less documented. This review aims to explore different conceptual approaches based on the electrophilic species involved in the reaction to produce stereoselective chiral allenes and styrenes, providing insights into recent advancements in the field. Emphasis is placed on works published since 2017, with detailed discussions on reaction mechanisms and examples from recent literature.
RESUMEN
A novel chiral phosphoric acid-catalyzed tandem regioselective 1,6-addition/double intramolecular nucleophilic addition annulation of the propargylic 3-methyleneindoles in situ generated from α-indolyl propargylic alcohols with 2-indolylmethanols has been developed. The methodology afforded the new chiral trifluoromethyl pentalenobisindoles bearing an all-carbon quaternary stereogenic center in generally good yields with excellent enantioselectivities.
RESUMEN
We present herein an enantioselective protocol for the chiral phosphoric acid-catalyzed addition of 3-arylisoxazol-5-amines to highly reactive 3-methide-3H-pyrroles to provide a diverse range of heterotriarylmethanes bearing an amino acid moiety in good yields (up to 97%) and high enantioselectivities (up to 93% ee) under mild conditions. The chiral spirocyclic phosphoric acid is crucial in converting the initial 1H-pyrrol-3-yl carbinols into reactive 3-methide-3H-pyrroles and obtaining the good enantiocontrol, thereby facilitating the desired enantioselective transformation.
RESUMEN
The organocatalytic asymmetric reactions of C2-unsubstituted racemic naphthyl-indoles with orthoalkynylnaphthols were employed to synthesize axially chiral styrenes connected to an axially chiral naphthyl-indole unit. Utilizing chiral phosphoric acid as the catalyst, these axially chiral styrenes were prepared in good yields (up to 96%) and excellent stereoselectivity (up to >99.9% ee, >20:1 dr, and >99:1 E/Z) in mild conditions. Moreover, further synthetic transformations were achieved with high yields and excellent stereocontrol.
RESUMEN
We developed a novel asymmetric Friedel-Crafts alkylation/transamidation tandem reaction for the enantio- and diastereoselective synthesis of pyrazolo[3,4-b]pyridin-6-ones bearing a -CF3 unit via synergistic chiral phosphoric acid and MgSO4 catalysis. This [3 + 3] annulation protocol allows the formation of trifluoromethylated pyrazolo[3,4-b]pyridin-6-ones with two adjacent tertiary stereocenters in moderate to high yields (up to 90%), enantioselectivities (up to 97% ee), and diastereoselectivities (up to >20:1 dr).
RESUMEN
An efficient organocatalytic conjugated addition reaction of pyrazol-3-ones with 3-trifluoroethylidene oxindoles has been developed for the synthesis of enantioenriched triflouromethylated indolin-2-ones bearing adjacent tertiary chiral centers in good yields and good to excellent diastereo- and enantioselectivities. The use of a newly developed chiral spirobiindane-derived squaramide catalyst is essential in achieving high diastereo- and enantioselectivities.
RESUMEN
The highly regio-, diastereo-, and enantioselective dearomatization reaction of 1-substituted 2-naphthols and ß,γ-alkynyl-α-imino esters with complete atom economy is disclosed via chiral phosphoric acid catalysis. This protocol provides facile and efficient access to asymmetric construction of a broad range of axially chiral allene-derived naphthalenones bearing quaternary stereocenters in good yields with high diastereoselectivities and enantioselectivities.