An organocatalytic enantioselective direct α-heteroarylation of aldehydes with isoquinoline N-oxides

Abstract

A new protocol for the enantioselective direct α-heteroarylation of aldehydes with isoquinoline N-oxides, via chiral enamine catalysis, has been successfully developed. High enantiomeric excesses and moderate to good yields were achieved for a variety of α-heteroarylated aldehydes.

Catalytic Enantioselective Synthesis of α‐Chiral Azaheteroaryl Ethylamines by Asymmetric Protonation

“…[1] Natural substances such as adrenaline,a mphetamine,h istamine,a nd thyroxine are critically important to human health and have been used as templates for the development of treatments for ab road range of disease states.A ccess to de novo chiral scaffolds has proven valuable for the development of new ligands for discrete targets (see Scheme 1a for examples).On heterocyclic scaffolds,n umerous approaches have been made to allow formation of the a-and b-stereocentre. [2,3] However,m ethods to directly access the a-stereocentre on the b-amino template are rare.Asymmetric hydrogenation is perhaps the most effective but requires prior synthesis of an enamine precursor, [4] while hydroamination is generally more effective intramolecularly. [5] Herein, we present amethod for the asymmetric synthesis of this important compound class based on achiral phosphoric acid (CPA) catalysed dearomatizing aza-Michael reaction/ rearomatizing asymmetric protonation of 1,1-vinyl azaheterocycles (Scheme 1b).…”

Catalytic Enantioselective α-Arylation of Carbonyl Enolates and Related Compounds

“…Also by asymmetric enamine catalysis, Fochi, Bernardi, and co-workers accomplished a new enantioselective direct α-heteroarylation of aliphatic aldehydes 124 with isoquinoline N -oxides 172 as heteroarylating reagents (Scheme ). The use of 20 mol % of Hayashi–Jørgensen catalyst 144a with 1.2 equiv of PyBroP (bromotripyrrolidino phosphonium hexafluorophosphate) afforded various α-heteroarylated aldehydes with good to excellent enantioselectivities that were subsequently transformed to the more stable α,β-unsaturated esters 173 through a Wittig process. Notably, the addition of PyBroP as an activating agent of N -oxides was crucial for this α-heteroarylation, because it could prevent catalyst quenching.…”

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

“…Substituted isoquinoline derivatives are considered as an important class of N-heterocyclic compounds, showing attractive physiological, biological and pharmacological activities [41][42][43][44][45]. Therefore, the feasibility of synthesizing isoquinoline derivatives using LSA-FAS-Cu as catalyst was investigated.…”