Asymmetric Construction of Functionalized 1,2-Dihydropyridine and Pyridine Derivatives with Adjacent Stereocenters via a Unified Metal-Free Catalytic Approach

Abstract

A novel asymmetric catalytic approach for the construction of enantioenriched functionalized 1,2-dihydropyridines and pyridine derivatives incorporating adjacent quaternary and tertiary stereocenters has been reported. This process involved a metal-free catalytic asymmetric allylic alkylation and a stereospecifically nonoxidative aromatization approach for the desired chiral molecules.

Construction of Acyclic Vicinal Tertiary and Quaternary Carbon Stereocenters via a Pd‐Catalyzed Allylic Alkylation of Stereodefined Polysubstituted Ketene Aminals

“…As a result, and despite the importance of vicinal tertiary and quaternary stereocenters in organic synthesis, there is a very limited arsenal of methods available to the practitioners for the installation of such vicinal stereocenters in acyclic systems (Scheme a) . The most common approaches for the diastereo‐ and enantioselective preparation of vicinal tertiary and quaternary carbon stereocenters within acyclic systems are the i) sigmatropic rearrangements including the recently reported traceless charge‐accelerated sulfonium rearrangement, ii) Pd‐catalyzed Heck arylation as a remote trigger for cyclopropane selective ring‐opening, iii) Michael additions iv) allylic alkylations of malonates equivalents (Scheme b) . In the last two examples, to control the stereochemistry of the enolate partner, only substrates allowing a chelated intermediate could be used.…”

Synthesis of Enantioenriched Vicinal Tertiary and Quaternary Carbon Stereogenic Centers within an Acyclic Chain

“…Then, a cyanide‐catalyzed domino sequence based on a Morita–Baylis–Hillman reaction where the terminal olefin undergoes the nucleophilic addition of the cyanide leads to the formation of an enolate. Finally, a diastereoselective acyl migration occurs triggering a final aromatization by elimination of the tertiary cyanide moiety (Scheme ) …”

“…An initial organocatalytic enantioselective allylic alkylation of allylic carbonates with dihydropyridines allows the formation of the two contiguous stereogenic centers with high selectivities.T hen, ac yanide-catalyzed domino sequence based on aM orita-Baylis-Hillman reaction where the terminal olefin undergoes the nucleophilic addition of the cyanide leads to the formation of an enolate.F inally, ad iastereoselective acyl migration occurs triggering af inal aromatization by elimination of the tertiary cyanide moiety (Scheme 12). [25]…”

Synthese enantiomerenangereicherter, vicinaler tertiärer und quartärer Kohlenstoff‐Stereozentren innerhalb einer acyclischen Kette

“…Anschließend erfolgt eine Cyanid‐katalysierte Dominosequenz aus einer Morita‐Baylis‐Hillman‐Reaktion, bei der das terminale Olefin eine nucleophile Addition durch das Cyanid erfährt, was zur Bildung eines Enolats führt. Abschließend findet eine diastereoselektive Acylwanderung statt, die eine Aromatisierung durch Eliminierung der tertiären Cyanideinheit auslöst (Schema ) …”

“…Abschließend findet eine diastereoselektive Acylwanderung statt, die eine Aromatisierung durch Eliminierung der tertiären Cyanideinheit auslçst (Schema 12). [25]…”