Catalytic Asymmetric Five‐Component Tandem Reaction: Diastereo‐ and Enantioselective Synthesis of Densely Functionalized Tetrahydropyridines with Biological Importance

Abstract

The first catalytic asymmetric five‐component tandem reactions of β‐keto esters, aromatic aldehydes and anilines have been established in the presence of a chiral phosphoric acid, affording densely functionalized tetrahydropyridines with concomitant generation of five σ bonds and two stereogenic centers in high diastereo‐ and enantioselectivities (up to >99:1 dr, 95:5 er). In addition, the first isolation and preparation of a diene species as the key intermediate of the reaction has been successfully realized, leading to the formation of the desired tetrahydropyridine via further condensation with in situ generated imine, which supported the proposed tandem [4+2] reaction pathway to some extent. This protocol not only represents the first enantioselective example of this five‐component tandem reaction, but also provides an unprecedented access to enantioenriched tetrahydropyridines with structural diversity, which holds great potential in medicinal chemistry.

Efficient and Eco‐Friendly One‐Pot Synthesis of Functionalized Furan‐2‐one, Pyrrol‐2‐one, and Tetrahydropyridine Using Lemon Juice as a Biodegradable Catalyst

“…Till now, methods which use catalysts such as bromodimethylsulfonium bromide (BDMS), molecular iodine, tetrabutylammoniumtribromide (TBATB), CAN, picric acid, ZrOCl 2. 8H 2 O, bismuth nitrate, LaCl 3 .7H 2 O, Zn(HSO 4 ) 2 , VCl 3 , Mg(HSO 4 ) 2 , chiral phosphoric acid, acetic acid, tungstophosphoric acid, L‐proline nitrate, B(C 6 F 5 ) 3 , Camphorsulfonic acid, silica gel, tartaric acid, silica sulfuric acid, β‐1‐Imidazole‐2,3,4,6‐tetrasulfonic‐D‐glucopyranosyl bisulfate ([Bmim‐G‐(SO 3 H) 4 ] + [HSO 4 ] − ), nano‐TiCl 4 /SiO 2 etc . have been used for the construction of THPD ring.…”

Catalytic One-Pot Double Asymmetric Cascade Reaction: Synthesis of Chlorinated Oxindoles and Geminal Diamines

“…Recently, the synergy of chiral phosphoric acids and efficient transition metal catalysts in enantiocontrolled reactions has allowed for more diverse synthetic transformations to occur in a single reaction pot. − AMCRs have been used effectively in synthesis due to their bond-forming efficiency and excellent stereoselectivity, along with the potential to quickly assemble complex products. , Although there are many advantages for AMCRs, the controlled enantioselective cascade of two different reactions by only one catalyst in one pot is still one of the remaining unmet challenges. In addition to the catalyst, various other factors must be taken into consideration for asymmetric cascade reactions such as solvent, substrates, and intermediates .…”

A Method of Calculating the Kamlet–Abboud–Taft Solvatochromic Parameters Using COSMO-RS

“…For a successful reaction the diketo-tautomer of 1 is required to react with p -anisidine before a Knoevenagel condensation and the final cycloaddition (Scheme 3) [41]. Therefore, polar solvents that increase diketo-tautomer concentrations (Figure 1b) provide higher yields (Figure 7c).…”