Xiu-Qin Dong

Highly anti-selective asymmetric nitro-mannich reactions catalyzed by bifunctional amine-thiourea-bearing multiple hydrogen-bonding donors.

Highly anti-selective and enantioselective nitro-Mannich reactions have been achieved for a broad spectrum of substrates catalyzed by chiral bifunctional multiple hydrogen-bonding-donor amine-thioureas. Multiple hydrogen-bonding donors play a significant role in accelerating reactions and improving yields, diastereoselectivities, and enantioselectivities.

Highly Enantioselective Direct Michael Addition of Nitroalkanes to Nitroalkenes Catalyzed by Amine−Thiourea Bearing Multiple Hydrogen-Bonding Donors

A highly diastereoselective and enantioselective Michael addition of nitroalkanes to nitroalkenes has been achieved by chiral bifunctional amine-thiourea catalyst bearing multiple hydrogen-bonding donors. This catalytic system performs well over a broad scope of substrates, furnishing various 1,3-dinitro compounds in high diastereoselectivity (up to 98:2) and excellent enantioselectivity (up to 99% ee) under mild conditions. Multiple hydrogen bonding donors play a significant role in accelerating reactions, improving diastereoselectivities and enantioselectivities.

Organocatalytic Asymmetric Sulfa-Michael Addition of Thiols to 4,4,4-Trifluorocrotonates

The first asymmetric sulfa-Michael addition of thiols to 4,4,4-trifluorocrotonates for the construction of a stereogenic center bearing a unique trifluoromethyl group and a sulfur atom has been achieved in high yields and excellent enantioselectivities with a 1 mol % bifunctional organocatalyst. Subsequent transformation led to the expedient preparation of enantioenriched thiochroman-4-one and the key intermediate of the potent inhibitor of MMP-3, (R)-γ-trifluoromethyl γ-sulfone hydroxamate.

Organocatalytic asymmetric domino sulfa-Michael–aldol reactions of 2-mercaptobenzaldehyde with α,β-unsaturated N-acylpyrazoles for the construction of thiochromane

An efficient protocol for the direct construction of bioactive thiochromanes was developed via a catalytic asymmetric cascade sulfa-Michael-aldol reaction of 2-mercaptobenzaldehyde with α,β-unsaturated N-acyl imides. The key to the present methodology is introducing a pyrazole moiety as H-bond acceptor, which allowed for better organization and activation and hence higher enantioselectivity.

Synthesis of Chiral β-Amino Nitroalkanes via Rhodium-Catalyzed Asymmetric Hydrogenation

The asymmetric hydrogenation of β-amino nitroolefins has been successfully achieved by rhodium/bis(phosphine)-thiourea L1 with excellent enantioselectivities and yields (up to 96% ee, 96% yield, >99% conversion, TON up to 1000) under mild conditions. Chiral β-amino nitroalkane products and their derivatives are versatile intermediates in organic synthesis.

Rhodium/Yanphos-Catalyzed Asymmetric Interrupted Intramolecular Hydroaminomethylation of trans-1,2-Disubstituted Alkenes

The first interrupted asymmetric hydroaminomethylation reaction was developed. The challenging trans-1,2-disubstituted olefins were employed as substrates, and a series of valuable chiral pyrrolidinones and pyrrolidines were obtained in high yields with high regioselectivities and excellent enantioselectivities. Several synthetic transformations were conducted, demonstrating the high synthetic utility of our method. A creative route for the synthesis of vernakalant and Enablex was also developed.

Catalytic asymmetric α-aldol reaction of vinylogous N-heterocyclic carbene enolates: formation of quaternary and labile tertiary stereocenters.

Simple N-heterocyclic carbene (NHC)-enolates are widely studied versatile species. However, their vinylogous siblings (i.e., vinylogous NHC-enolates) have been much less studied. Here we disclose the first catalytic asymmetric α-aldol reaction of vinylogous NHC-enolates. With trifluoropyruvate as the carbon electrophile, the efficient C-C bond formation process displays not only complete α-regioselectivity but also excellent stereocontrol over the two newly established challenging stereocenters (one quaternary and the other labile tertiary), furnishing a range of highly enantioenriched β,γ-unsaturated α-fluoroalkylated esters.

Metalorganocatalysis: cooperating transition-metal catalysis and organocatalysis through a covalent bond

Asymmetric catalysis has grown rapidly and made considerable progress in the last few decades, but there still remain significantly unachievable reactions through either organocatalysis or transition-metal catalysis alone. The concept of combination of transition-metal catalysis with organocatalysis emerged as a powerful strategy for developing asymmetric catalysis, and has attracted great attention. In order to avoid the incompatibility existing in catalysts, substrates, intermediates and solvents through combining transition-metal catalysis and organocatalysis, it is urgently necessary to develop a new catalytic strategy to resolve these problems. Therefore, we are devoted to designing a series of novel bifunctional catalysts based upon the synergistic activation strategy via cooperating transition metal-catalysis and organocatalysis through a covalent bond forming a bifunctional molecule. In this review, this momentous strategy is illustrated with several recent outstanding examples and prospective promising applications, with the aim of elaborating the synthetic utilities and potentialities of this concept as a powerful tool in organic synthesis.

Recent progress in rhodium-catalyzed hydroaminomethylation

Hydroaminomethylation is a perfect reaction for converting alkenes into valuable amines with high atom economy in the presence of the syngas and amines. Significant progress has been made in the past decades; however, there still remain challenges for the control of chemo- and regioselectivity concurrently. Rhodium has proved to be a better metal in hydroaminomethylation for higher activity in hydroformylation and hydrogenation steps. Although promising results were shown by unmodified rhodium catalysts, phosphine ligand modified rhodium complexes generally displayed better activity and regioselectivity. Among the phosphorus ligands developed, tetraphosphorus ligands exhibited much better regioselectivity due to their stronger chelating ability. Apart from the phosphorus ligands, carbene and nitrogen-containing ligands have also been developed which showed good activity due to the promotion of the hydrogenation step. Although non-enantioselective hydroaminomethylation reactions have been intensively studied, reports on asymmetric hydroaminomethylation are rare. Direct asymmetric hydroaminomethylation is very challenging and only reaction systems with two different catalysts showed promising results.

Iridium-Catalyzed Asymmetric Hydrogenation of Ketones with Accessible and Modular Ferrocene-Based Amino-phosphine Acid (f-Ampha) Ligands

A series of tridentate ferrocene-based amino-phosphine acid (f-Ampha) ligands have been successfully developed. The f-Ampha ligands are extremely air stable and exhibited excellent performance in the Ir-catalyzed asymmetric hydrogenation of ketones (full conversions, up to >99% ee, and 500 000 TON). DFT calculations were performed to elucidate the reaction mechanism and the importance of the -COOH group. Control experiments also revealed that the -COOH group played a key role in this reaction.