Caiyou Chen

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.

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.

A Novel Triphosphoramidite Ligand for Highly Regioselective Linear Hydroformylation of Terminal and Internal Olefins

The first triphosphorus ligand has been designed and synthesized for highly regioselective linear hydroformylations. A very high l/b ratio (up to 471, 99.8% linear selectivity) was obtained in the linear hydroformylation of representative terminal and internal olefins. For the range of substrates tested, the regioselectivities achieved utilizing the novel triphosphoramidite ligand were much better than those of the bisphosphoramidite ligand and close to those of the tetraphosphoramidite ligand.

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.

Synthesis and application of a new triphosphorus ligand for regioselective linear hydroformylation: a potential way for the stepwise replacement of PPh3 for industrial use

A new triphosphorus ligand, Tribi, was developed for the regioselective linear hydroformylation of terminal and internal olefins. It was shown to have excellent catalytic activity and regioselectivity. More importantly, the synthesis of the new triphosphorus ligand was scaled-up (>140 g scale) for practical industrial use. An effective method was also developed for the stepwise replacement of PPh3 by Tribi for potential industrial use.

Selective Rhodium-Catalyzed Hydroformylation of Alkynes to α,β-Unsaturated Aldehydes with a Tetraphosphoramidite Ligand.

A tetraphosphoramidite ligand was successfully applied to a Rh-catalyzed hydroformylation of various symmetrical and unsymmetrical alkynes to afford corresponding α,β-unsaturated aldehyde products in good to excellent yields (up to 97% yield). Excellent chemo- and regioselectivities and high activities (up to 20 000 TON) were achieved. The corresponding α,β-unsaturated aldehyde products can be transformed into many useful and important organic molecules, such as indenamine derivatives and lukianol pyrroles. This great performance makes the hydroformylation of alkynes highly practical with great potential.

Highly stereoselective synthesis and application of P-chiral ferrocenyl bisphosphorus ligands for asymmetric hydrogenation

New, efficient and highly stereoselective methods were developed for the synthesis/modification of Wudaphos type ligands. It was found that the “three hindered quadrant” model is crucial to ensure high enantiomeric control and that the substituents on the phosphine atom should be electron rich to increase the reactivity. Moreover, a new SPO-Wudaphos ligand was developed, which exhibited good to excellent enantioselectivities in the asymmetric hydrogenation of α-methylene-γ-keto carboxylic acids.

Chiral Ligands for Rhodium-Catalyzed Asymmetric Hydroformylation: A Personal Account.

Asymmetric hydroformylation represents one of the most efficient routes for the preparation of chiral aldehydes from alkenes in the presence of syngas in a perfect atom-economic way. During the past few decades, a variety of chiral ligands have been developed for the asymmetric hydroformylation. However, only a few ligands exhibit good performance in terms of the regio- and enantioselectivities. Additionally, for the chiral ligands developed up to now, only limited substrates were tolerated and no examples have led to the application of the asymmetric hydroformylation reaction on a commercial scale due to several technical challenges. This account provides a brief introduction of the current efficient chiral ligands for asymmetric hydroformylation and the ongoing efforts we have made in this field.

Rh/SPO-WudaPhos-Catalyzed Asymmetric Hydrogenation of α-Substituted Ethenylphosphonic Acids via Noncovalent Ion-Pair Interaction

Asymmetric hydrogenation of α-substituted ethenylphosphonic acids has been successfully achieved by Rh/ferrocenyl chiral bisphosphorus ligand (SPO-Wudaphos) through noncovalent ion-pair interaction between the substrate and catalyst under mild reaction conditions without base. A series of chiral phosphonic acids were obtained with excellent results (up to 98% ee, >99% conversion, 2000 TON). Moreover, the control experiments showed that the noncovalent ion-pair interaction was critical in this asymmetric hydrogenation.

Rh/Wudaphos-Catalyzed Asymmetric Hydrogenation of Sodium α-Arylethenylsulfonates: A Method To Access Chiral α-Arylethylsulfonic Acids

A highly enantioselective hydrogenation of various sodium α-arylethenylsulfonates catalyzed by Rh/chiral ferrocenyl bisphosphorus ligand (Wudaphos) was successfully developed to construct a series of chiral α-arylethylsulfonic acids in the presence of CF3SO3H with full conversion and good to excellent enantioselectivity (>99% conversion, up to 96% ee) under mild reaction conditions for the first time. Moreover, the control experiment results showed that the non-covalent ion pair interaction between the α-arylethenylsulfonic acid and the Wudaphos ligand plays an important role in this asymmetric hydrogenation system.