An oxidative γ-functionalization of enals under N-heterocyclic carbene (NHC) catalysis to give unsaturated δ-lactones is disclosed. Enantioselectivity control involving the relatively remote enal γ-carbon was achieved via Lewis acid [Sc(OTf)(3) or combined Sc(OTf)(3)/Mg(OTf)(2)] and NHC cooperative catalysis.

The first N-Heterocyclic Carbene (NHC) mediated activation of stable carboxylate esters to generate enolate intermediates is disclosed. The catalytically generated arylacetic ester enolates undergo enantioselective reactions with α,β-unsaturated imines.

Aryl aldehyde activation: Oxidative activation of 2-methylindole-3-carboxaldehyde (I) through N-heterocyclic carbene (NHC) organocatalysis generates heterocyclic ortho-quinodimethane (II) as a key intermediate. This intermediate then undergoes formal [4+2] cycloaddition with trifluoromethyl ketones or isatins to form polycyclic lactones containing a quaternary carbon center.

A direct coupling of unprotected indoles and α-halo ketones via in situ generated oxyallyl cation intermediates is described. The reactions efficiently afford α-indole carbonyl compounds with good to quantitative yields.

Carbene-catalyzed reaction of carboxylic esters has the potential to offer effective synthetic solutions that cannot be readily achieved by using the more conventional aldehyde-type substrates. Here we report the first carbene-catalyzed dynamic kinetic resolution of α,α-disubstituted carboxylic esters with up to 99:1 er and 99% yield. The present study clearly illustrates the unique power of carbene-catalyzed reactions of readily available and easy to handle carboxylic esters.

A direct α-functionalization of simple aldehydes under N-Heterocyclic Carbene (NHC) catalysis and direct generation of ester enolate equivalents from nonfunctionalized aldehydes are disclosed. The catalysis involves selective enolate generation from an oxidatively generated NHC-bounded ester intermediate as a key step. The ester enolate intermediates undergo stereoselective reactions with enones and trifluoromethyl ketones.

The research in the field of asymmetric carbene organic catalysis has primarily focused on the activation of carbon atoms in non-aromatic scaffolds. Here we report a reaction mode of carbene catalysis that allows for aromatic aldehyde activation and remote oxygen atom functionalization. The addition of a carbene catalyst to the aldehyde moiety of 2-hydroxyl aryl aldehyde eventually enables dearomatization and remote OH activation. The catalytic process generates a type of carbene-derived intermediate with an oxygen atom as the reactive centre. Inexpensive achiral urea co-catalyst works cooperatively with the carbene catalyst, leading to consistent enhancement of the reaction enantioselectivity. Given the wide presence of aromatic moieties and heteroatoms in natural products and synthetic functional molecules, we expect our reaction mode to significantly expand the power of carbene catalysis in asymmetric chemical synthesis.

A convergent, organocatalytic asymmetric aminomethylation of α,β-unsaturated aldehydes by N-heterocyclic carbene (NHC) and (in situ generated) Brønsted acid cooperative catalysis is disclosed. The catalytically generated conjugated acid from the base plays dual roles in promoting the formation of azolium enolate intermediate, formaldehyde-derived iminium ion (as an electrophilic reactant), and methanol (as a nucleophilic reactant). This redox-neutral strategy is suitable for the scalable synthesis of enantiomerically enriched β(2) -amino acids bearing various substituents.