Zhaobin Han

The NH Functional Group in Organometallic Catalysis

The organometallic approach is one of the most active topics in catalysis. The application of NH functionality in organometallic catalysis has become an important and attractive concept in catalyst design. NH moieties in the modifiers of organometallic catalysts have been shown to have various beneficial functions in catalysis by molecular recognition through hydrogen bonding to give catalyst-substrate, ligand-ligand, ligand-catalyst, and catalyst-catalyst interactions. This Review summarizes recent progress in the development of the organometallic catalysts based on the concept of cooperative catalysis by focusing on the NH moiety.

Catalytic Hydrogenation of Cyclic Carbonates: A Practical Approach from CO2 and Epoxides to Methanol and Diols

Two birds with one stone: the simultaneous production of two important bulk chemicals, methanol and ethylene glycol, from CO(2) and ethylene oxide has been achieved under mild conditions by the highly efficient homogeneous catalytic hydrogenation of ethylene carbonate in the presence of a (PNP)Ru(II) catalyst.

Spiro[4,4]‐1,6‐nonadiene‐Based Phosphine–Oxazoline Ligands for Iridium‐Catalyzed Enantioselective Hydrogenation of Ketimines

From imines to amines through catalysis by Ir(I) complexes of a new type of P,N ligand (see scheme): This reaction affords the corresponding optically active amines with up to 98 % ee and has also been used with perfect stereoselectivity in the asymmetric synthesis of sertraline (1), an important antidepressant chiral drug.

Spiro Skeletons: A Class of Privileged Structure for Chiral Ligand Design

This Focus Review highlights the exciting results obtained in the area of asymmetric catalysis using spirobiindane- or spirobifluorene-based chiral ligands. The spiro, mono, and bidentate ligands have been successfully applied in a wide range of transition-metal-catalyzed asymmetric reactions, including hydrogenations, carbon-carbon and carbon-heteroatom coupling reactions, with superior or comparable enantioselectivities to those obtained by using the related ligands bearing other backbones, thus proving that the spiro skeleton is a type of privileged structure for chiral ligand design. It is expected that the spiro concept for chiral ligand design will stimulate the future efforts to understand the features that account for their broad applicability and to apply this understanding to seek new privileged chiral ligands and catalysts.

Highly Efficient Ruthenium‐Catalyzed N‐Formylation of Amines with H2 and CO2

A highly efficient catalyst system based on ruthenium-pincer-type complexes has been discovered for N-formylation of various amines with CO2 and H2, thus affording the corresponding formamides with excellent productivity (turnover numbers of up to 1,940,000 in a single batch) and selectivity. Using a simple catalyst recycling protocol, the catalyst was reused for 12 runs in N,N-dimethylformamide production without significant loss of activity, thus demonstrating the potential for practical utilization of this cost-effective process. A one-pot two-step procedure for hydrogenation of CO2 to methanol via the intermediacy of formamide formation has also been developed.

Catalytic Asymmetric Synthesis of Aromatic Spiroketals by SpinPhox/Iridium(I)‐Catalyzed Hydrogenation and Spiroketalization of α,α′‐Bis(2‐hydroxyarylidene) Ketones

Recently, the chemistry of chiral aromatic spiroketals has received much attention because they are key substructures in biologically active natural products, pharmaceuticals, and chiral ligands in transition-metal-catalyzed reactions. Although several methods for the preparation of aromatic spiroketals have been reported, the direct catalytic, enantioselective synthesis of aromatic spiroketals has not yet been achieved. On the other hand, transition-metalcatalyzed asymmetric hydrogenations have long held a respected position in modern organic synthesis. In particular, the iridium-catalyzed asymmetric hydrogenation of the C=C bonds of either functionalized or unfunctionalized olefin derivatives has lately been an important topic in asymmetric catalysis. We have recently reported a class of highly efficient iridium(I) catalyst complexes with spiro[4.4]-1,6nonadiene-based chiral phosphine–oxazoline ligands (SpinPHOX, 1) for the enantioselective hydrogenation of N-aryl or alkyl imines and a-aryl-b-substituted acrylic acids. Herein, we report the first catalytic enantioselective synthesis of aromatic spiroketals 2 through the SpinPHOX/Ir-promoted asymmetric hydrogenation of a,a’-bis(2-hydroxyarylidene) ketones and spiroketalization of hydrogenation products.

Spiroketal-Based Diphosphine Ligands in Pd-Catalyzed Asymmetric Allylic Amination of Morita–Baylis–Hillman Adducts: Exceptionally High Efficiency and New Mechanism

Exceptionally high activity (with a TON up to 4750) of the palladium complexes of SKP ligand was discovered in the catalysis of asymmetric allylic amination of MBH adducts with aromatic amines. A comprehensive mechanistic study indicates that the unique structural features of the SKP ligand, with a long P···P distance in its solid-state structure, were favorable for allowing two P atoms to play a bifunctional role in the catalysis. Herein, one of the P atom forms a C-P σ-bond with the terminal carbon atom of allyl moiety as a Lewis base, and an alternative P atom coordinates to Pd atom. The cooperative action of organo- and organometallic catalysis discovered in the present catalytic system is most likely responsible for its high activity, as well as excellent regio- and enantioselectivities. The mechanism disclosed in the present catalytic system is distinct from most of the currently recognized mechanisms for Pd-catalyzed allylic substitutions.

SpinPhox/Iridium(I)‐Catalyzed Asymmetric Hydrogenation of Cyclic α‐Alkylidene Carbonyl Compounds

Optically active medium-sized cyclic carbonyl compounds bearing an α-chiral carbon center are of interest in pharmaceutical sciences and asymmetric synthesis. Herein, SpinPhox/Ir(I) catalysts have been demonstrated to be highly enantioselective in the asymmetric hydrogenation of the CC bonds in the exocyclic α,β-unsaturated cyclic carbonyls, including a broad range of α-alkylidene lactams, unsaturated cyclic ketones, and lactones. It is noteworthy that the procedure can be successfully used in the asymmetric hydrogenation of the challenging α-alkylidenelactam substrates with six- or seven-membered rings, thus affording the corresponding optically active carbonyl compounds with an α-chiral carbon center in generally excellent enantiomeric excesses (up to 98 % ee). Synthetic utility of the protocol has also been demonstrated in the asymmetric synthesis of the anti-inflammatory drug loxoprofen and its analogue, as well as biologically important ε-aminocaproic acid derivatives.

Highly Regio- and Enantioselective Alkoxycarbonylative Amination of Terminal Allenes Catalyzed by a Spiroketal-Based Diphosphine/Pd(II) Complex

An enantioselective alkoxycarbonylation-amination cascade process of terminal allenes with CO, methanol, and arylamines has been developed. It proceeds under mild conditions (room temperature, ambient pressure CO) via oxidative Pd(II) catalysis using an aromatic spiroketal-based diphosphine (SKP) as a chiral ligand and a Cu(II) salt as an oxidant and affords a wide range of α-methylene-β-arylamino acid esters (36 examples) in good yields with excellent enantioselectivity (up to 96% ee) and high regioselectivity (branched/linear > 92:8). Preliminary mechanistic studies suggested that the reaction is likely to proceed through alkoxycarbonylpalladation of the allene followed by an amination process. The synthetic utility of the protocol is showcased in the asymmetric construction of a cycloheptene-fused chiral β-lactam.

Palladium-Catalyzed Asymmetric Construction of Vicinal Tertiary and All-Carbon Quaternary Stereocenters by Allylation of β-Ketocarbonyls with Morita–Baylis–Hillman Adducts

Palladium-catalyzed regio-, diastereo-, and enantioselective allylic alkylation of β-ketocarbonyls with Morita-Baylis-Hillman adducts has been developed using a spiroketal-based diphosphine (SKP) as the ligand, thus affording a range of densely functionalized products bearing vicinal tertiary and all-carbon quaternary stereodyad in high selectivities. The utility of the protocol was demonstrated by the facile synthesis of some complex molecules by simple product transformations.