An efficient dual catalytic system composed of a chiral primary amine and a palladium complex was developed to promote the direct asymmetric allylic alkylation (AAA) of β-ketocarbonyl compounds. In particular, the synergistic dual catalytic system enabled the AAA reaction of challenging acyclic aliphatic ketones, such as β-ketocarbonyl compounds and 1,3-diketones.

An efficient dual catalytic system composed of a chiral primary amine and a palladium complex was developed to promote the direct asymmetric allylic alkylation (AAA) of β-ketocarbonyl compounds. In particular, the synergistic dual catalytic system enabled the AAA reaction of challenging acyclic aliphatic ketones, such as β-ketocarbonyl compounds and 1,3-diketones.

We present herein a mechanistic investigation by nanoelectrospray ionization mass spectrometry of copper-catalyzed aerobic oxidative processes involved in the N-nitrosocarbonyl aldol reaction of N-hydroxycarbamates. Protonated amine and copper as charge-tags aided the detection of reaction intermediates, which verified the enamine mechanism together with a competing enol process. Our experimental results reveal that the copper-catalyzed aerobic oxidation of N-hydroxycarbamates may proceed through an autoxidation catalytic mechanism in which a CbzNHO^. radical abstracts a hydrogen from the bound N-hydroxycarbamate to release the nitroso intermediate through a bimolecular hydrogen-atom transfer. In this process, the chiral diamine also works as a ligand for copper to facilitate the aerobic oxidative step. The dual role of the chiral vicinal diamine as both an aminocatalyst and a bidentate ligand was finally uncovered.

We report the first example of the enantioselective conjugate addition of alkenes (aromatic enamines) to enones catalyzed by chiral primary amines. The reactions encompass a plethora of α,β-enones including difficult α-substituted vinyl ketones to give vinylation adducts in high yields with good enantioselectivity. The methodology is of synthetic potential in accessing chiral functional materials.

A simple and direct α-allylic alkylation of unmodified aldehydes with allylic alcohols catalyzed by primary amine/Br⊘nsted acid has been developed. The N,N-dimethylethylenediamine/TfOH was identified as the optimal catalyst to promote this transformation via an enamine process in high yields (up to 88%) and with good diastereoselectivities (up to 9:1).

We describe herein an unprecedented asymmetric α-amination of β-ketocarbonyls under aerobic conditions. The process is enabled by a simple chiral primary amine through the coupling of a catalytic enamine ester intermediate and a nitrosocarbonyl (generated in situ) derived from N-hydroxycarbamate. The reaction features high chemoselectivity and excellent enantioselectivity for a broad range of substrates.

A Lewis acid in the presence of an anionic phosphate ligand enables the addition of alkenes to α,β-enones. The ligand facilitates selective β-proton elimination by suppressing competing pathways, thus leading to vinylation adducts in high yields (up to 99 %) for a broad range of substrates.

We describe herein an unprecedented asymmetric α-amination of β-ketocarbonyls under aerobic conditions. The process is enabled by a simple chiral primary amine through the coupling of a catalytic enamine ester intermediate and a nitrosocarbonyl (generated in situ) derived from N-hydroxycarbamate. The reaction features high chemoselectivity and excellent enantioselectivity for a broad range of substrates.

We described herein a catalyst-free visible-light photolytic protocol for the imidation of arenes and heteroarenes. N-Bromosaccharin was identified as a viable and chemoselective nitrogen radical precursor that undergoes controllable homolytic cleavage under ambient light irradiation. The reaction can be applied to a number of arenes and heteroarenes with good chemo- and regioselectivity. Mechanistic studies revealed that radical chain termination by electron transfer-proton transfer (ET-PT) is the leading productive pathway for the reaction.

Enantioselective protonation with a catalytic enamine intermediate represents a challenging, yet fundamentally important process for the synthesis of α-chiral carbonyls. We describe herein chiral primary-amine-catalyzed conjugate additions of indoles to both α-substituted acroleins and vinyl ketones. These reactions feature enamine protonation as the stereogenic step. A simple primary–tertiary vicinal diamine 1 with trifluoromethanesulfonic acid (TfOH) was found to enable both of the reactions of acroleins and vinyl ketones with good activity and high enantioselectivity. Detailed mechanistic studies reveal that these reactions are rate-limiting in iminium formation and they all involve a uniform H₂O/acid-bridged proton transfer in the stereogenic steps but divergent stereocontrol modes for the protonation stereoselectivity. For the reactions of α-branched acroleins, facial selections on H₂O-bridged protonation determine the enantioselectivity, which is enhanced by an OH⋅⋅⋅π interaction with indole as uncovered by DFT calculations. On the other hand, the stereoselectivity of the reactions with vinyl ketones is controlled according to the Curtin–Hammett principle in the CC bond-formation step, which precedes a highly stereospecific enamine protonation.

A mechanistic study of the tert-aminocyclization reaction was performed by using DFT calculations and labeling experiments. The results showed that the reaction proceeded through a rate-limiting-, stereospecific-, and suprafacial 1,5-H-transfer pathway, followed by a barrier-less CC bond formation. The mode of stereocontrol for facial selection could be ruled out owing to the high activation energy of CN bond rotation. The intrinsic feature of this Lewis acid activation was found to be the activation of the LUMO, as well as an intermediate-stabilization effect. The catalytically active species was believed to be a 1:1 complex of phosphoric acid and MgCl₂, which was stabilized by a H⋅⋅⋅Cl hydrogen bond. The chiral catalytic complex selectively recognizes and activates one of the two helical conformations of substrate A, required for 1,5-suprafacial H-transfer, which dictates the stereoselectivity of the forming products.

The first primary aminocatalytic direct cross-aldol reaction of acetaldehyde is presented. Among the various vicinal diamines screened, the L-tert-leucine derivative 1c in conjunction with (H₄SiW₁₂O₄₀)_0.25 was identified as the optimal catalyst; good catalytic activity (up to 99 % yield in 4 h), and high enantioselectivities (up to 92 % ee) were achieved for a range of donors, including aromatic aldehydes and isatin derivatives. Aqueous acetaldehyde solution and paraldehyde can be conveniently applied in this system.

A simple alkylthiourea was found to be an effective catalyst for the Michael addition reaction of 3-substituted oxindole to nitroolefins. A number of 3,3′-substituted oxindole derivatives, which have two vicinal quaternary-tertiary chiral centers were synthesized with up to 99% yield, 19:1 dr and 98% ee.

A highly enantioselective Michael addition of 3-substituted benzofuran-2(3H)-ones to chalcones catalyzed by a chiral bifunctional thiourea was developed. Several chiral 3,3′-substituted benzofuran-2(3H)-ones derivatives, bearing adjacent quaternary-tertiary stereocenters, were efficiently synthesized with excellent enantioselectivities.

Pyrrolidine-derived functionalized chiral ionic liquids (FCILs) have been found to catalyze asymmetric S_N1 α-alkylations of ketones and aldehydes with up to 99 % yield, >99:1 dr and 87 % ee. The FCIL catalysts enable S_N1 α-alkylations of cyclic ketones, particularly of 3- and 4-substituted cyclohexanones with excellent diastereoselectivity and good enantioselectivity, featuring unprecedented desymmetrization and kinetic resolution processes for these types of asymmetric reaction. Full details of this study as well as the proposed enamine transition-state are presented.

1,1-Disubstituted terminal alkenes remain challenging substrates in asymmetric epoxidation reactions. In this study, chiral primary amines are shown to catalyze the asymmetric epoxidation of α-substituted acroleins, a versatile type of 1,1-disubstituted terminal alkene. Among various chiral primary amines explored, the chiral primary-tertiary vicinal diamine derived from trans-1,2-diphenylethane-1,2-diamine is identified as the optimal catalyst, which, in combination with 5-sulfosalicyclic acid (5-SSA), exhibits good catalytic activity (up to 95 % yield) and enantioselectivity (up to 88 % ee). Aqueous 2 M sodium chloride was found to be the optimal reaction media.

Solid acid–chiral amine hybrids have been synthesized and explored as recyclable and reusable enamine-type asymmetric catalysts. Simple chiral amine–polyoxometalate (CA–POM) hybrids were identified as the optimal catalysts to promote a range of enamine-based transformations with high activity and excellent stereoselectivity under either neat or aqueous conditions. A catalyst loading as low as 0.33 mol-% (1 mol-% loading of chiral amine) was sufficient to achieve fast reactions and high stereoselectivities. Under both conditions, the CA–POM hybrid catalysts could be easily recycled and reused up to seven times with essentially unchanged stereoselectivity, although diminished activity was observed upon extensive reuse, especially under aqueous conditions.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

A new strategy for the immobilization of iminium organocatalysts through the acid–base assembly of multidentate chiral primary amines and solid polyacids is presented. A suitable structurally distinctive C₂-symmetric chiral primary amine (CPA) was identified in this study and the optimal CPA–POM hybrid obtained catalyzed the Diels–Alder cycloaddition of α-substituted acroleins in high yields and fair-to-high selectivity under aqueous conditions. The primary amine in the metal–organic-framework (MOF)-like catalyst acted as the catalytic center as well as multidentate basic centers, whereas phosphotungstic acid played dual roles as both catalyst anchors and modulators of the activity and stereoselectivity. Furthermore, the MOF-like catalyst showed both high reactivity and physical stability and thus could be recycled and reused six times with only a small loss of activity and selectivity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

By judiciously anchoring functional groups onto chiral ionic liquids, functionalized chiral ionic liquids (FCILs) are emerging as a new type of asymmetric organocatalysts and nonclassical chiral ligands. This Focus Review highlights the applications of FCILs from the viewpoint of asymmetric catalysis. We focus mainly on the de novo designed and synthesized FCILs which likely still maintain the typical ionic liquids properties, and in a few cases relevant ionic liquid immobilized chiral catalysts are briefly discussed.

Hydrogen-bonding catalysts have been found to catalyze one-pot three-component reactions of pyruvate, anilines and aldehydes to afford versatile 3-amino-1,5-dihydro-2H-pyrrol-2-ones in high yields. Both, thioureas and phosphoric acids are viable catalysts for these reactions and have comparable activity. The corresponding chiral thioureas and phosphoric acids have also been used in these three-component reactions to give pyrrol-2-ones in high yields and with moderate enantioselectivities.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A new strategy for the immobilization of asymmetric organocatalysts by combining polystyrene (PS)/sulfonic acids and chiral amines in situ through acid–base interactions is presented. The PS/sulfonic acids play a dual role as catalyst anchors and modulators for activity and stereoselectivity. Different types of polymeric sulfonic acids were examined and 1 % divinylbenzene (DVB) cross-linked PS/sulfonic acid 1 e with a medium loading of sulfonic acid moieties was found to be the optimal support. Furthermore, the noncovalency of this system allows combinatorial screening of optimal catalysts for the targeted reactions. In this regard, highly efficient and enantioselective heterogeneous catalysts were identified for the asymmetric direct aldol and Michael addition reactions. The catalysts could be easily recovered by filtration and reused for six cycles with similar stereoselectivity but slightly decreased activity. Significantly, the deactivated catalysts could be regenerated following an acidic washing/amine recharging procedure.