Pd/Cu Catalyzed Asymmetric Allylation for Stereodivergent Synthesis of Glutamic Acid Derivatives.

A synergistic Pd/Cu catalyst system has been developed for stereodivergent transformation of Morita-Baylis-Hillman (MBH) carbonates and Schiff bases derived from simple amino acids to afford a series of optically active β-branched γ-methyleneglutamic acid derivatives with adjacent tertiary/tertiary and quaternary/tertiary stereocenters in high yields (up to 96 %) with excellent diastereo- and enantioselectivities (>20/1 dr and >99 % ee in most cases) under mild conditions. The use of SKP ligand is disclosed to be crucial for the success of the transformation, and in particular allowing the reaction to proceed at low catalyst loading (0.02 mol % for Pd and 0.

Ruthenium-Catalyzed Carbocycle-Selective Hydrogenation of Fused Heteroarenes.

The homogeneous catalytic hydrogenation of benzo-fused heteroarenes generally provides partially hydrogenated products wherein the heteroaryl ring is preferentially reduced, such as quinoline hydrogenation, leading to 1,2,3,4-tetrahydroquinoline. Herein, we report a carbocycle-selective hydrogenation of fused -heteroarenes (quinoline, isoquinoline, quinoxaline, etc.) using the Ru complex of a chiral spiroketal-based diphosphine (SKP) as the catalyst, affording the corresponding 5,6,7,8-tetrahydro products in high chemoselectivities.

Phosphine-catalyzed divergent domino processes between γ-substituted allenoates and carbonyl-activated alkenes.

Highly enantioselective and chemodivergent domino reactions between γ-substituted allenoates and activated alkenes have been developed. In the presence of NUSIOC-Phos, triketone enone substrates smoothly reacted with γ-substituted allenoates to form bicyclic furofurans in good yields with high stereoselectivities. Alternatively, the reaction between diester-activated enone substrates and γ-substituted allenoates formed chiral conjugated 1,3-dienes in good yields with excellent enantioselectivities.

A Type of Structurally Adaptable Aromatic Spiroketal Based Chiral Diphosphine Ligands in Asymmetric Catalysis.

ConspectusWhile spectacular successes have been achieved in homogeneous catalysis with the use of achiral diphosphine ligands featuring a wide natural bite angle, such as XantPhos, chiral diphosphines that can induce a large P-M-P bite angle in their transition metal complexes are conspicuously less explored in asymmetric catalysis, probably due to the challenges in the identification and efficient construction of a suitable chiral backbone. In the past decade, a highly efficient synthesis of chiral aromatic spiroketals and the corresponding diphosphine ligands (SKPs) has been developed in this group.Based on a one-pot catalytic tandem double asymmetric hydrogenation-spiroketalization ring-closure reaction sequence, these SKP ligands featuring an extraordinarily long P···P distance and a flexible backbone have been readily prepared in large scale.

Iridium-Catalyzed Enantioselective Hydrogenation of Indole and Benzofuran Derivatives.

Enantioselective hydrogenation of a broad spectrum of N-, O-, and S-containing aromatic benzoheterocycles or nonaromatic unsaturated heterocycles has been realized by using an Ir/SpinPHOX (SpinPHOX=spiro[4,4]-1,6-nonadiene-based phosphine-oxazoline) complex as the catalyst, affording an array of the corresponding chiral benzoheterocycles (30 examples) with excellent enantioselectivities (>99 % ee in most cases) and turnover numbers up to 500.

Manganese-Catalyzed anti-Selective Asymmetric Hydrogenation of α-Substituted β-Ketoamides.

A Mn-catalyzed diastereo- and enantioselective hydrogenation of α-substituted β-ketoamides has been realized for the first time under dynamic kinetic resolution conditions. anti-α-Substituted β-hydroxy amides, which are useful building blocks for the synthesis of bioactive molecules and chiral drugs, were prepared in high yields with excellent selectivity (up to >99 % dr and >99 % ee) and unprecedentedly high activity (TON up to 10000). The origin of the excellent stereoselectivity was clarified by DFT calculations.

Highly Enantioselective [3 + 2] Annulation of 3-Butynoates with β-Trifluoromethyl Enones Promoted by an Amine-Phosphine Binary Catalytic System.

We report a highly enantioselective [3 + 2] annulation between 3-butynoates and β-trifluoromethyl enones, furnishing trifluoromethylated cyclopentenes with three contiguous stereogenic centers in good yields, high diastereoselectivities, and excellent enantioselectivities. A unique catalytic system consisting of a simple amine and a chiral phosphine was devised, and the synergistic play of Lewis basic amine and phosphine was crucial for alkyne isomerization and subsequent cyclization. The protocol disclosed herein allows facile activation of 3-butynoates in phosphine-mediated asymmetric transformations.

Cyclohexyl-Fused, Spirobiindane-Derived, Phosphine-Catalyzed Synthesis of Tricyclic γ-Lactams and Kinetic Resolution of γ-Substituted Allenoates.

A C-symmetric chiral phosphine catalyst, NUSIOC-Phos, which can be easily derived from cyclohexyl-fused spirobiindane, was introduced. A highly enantioselective domino process involving pyrrolidine-2,3-diones and γ-substituted allenoates catalyzed by NUSIOC-Phos has been disclosed. Diastereospecific tricyclic γ-lactams containing five contiguous stereogenic centers were obtained in high yields and with nearly perfect enantioselectivities.

Ir-Catalyzed Double Asymmetric Hydrogenation of 3,6-Dialkylidene-2,5-diketopiperazines for Enantioselective Synthesis of Cyclic Dipeptides.

An Ir/spiro[4,4]-1,6-nonadiene-based phosphine-oxazoline ligand (SpinPHOX) complex-catalyzed double asymmetric hydrogenation of 3,6-dialkylidene-1,4-dimethylpiperazine-2,5-diones has been developed, providing efficient and practical access to a wide variety of chiral 3,6-disubstituted-2,5-diketopiperazines in high yields with exclusive cis-diastereo- and excellent enantioselectivities (>99% de, up to 98% ee). The synthetic utilities of the protocol have been demonstrated in a gram scale synthesis of 6a and efficient construction of chiral products 8, 14, and 17 as well as a 2-butenyl-bridged bicyclic diketopiperazine 10 and hydroxydiketopiperazine 11. With an analogous achiral Ir catalyst, the hydrogenation of enantiopure monohydrogenated intermediate 7a gave cis-6a as the only product, indicating that the second-step hydrogenation of the titled transformation is a chiral substrate controlled process.

Lutidine-Based Chiral Pincer Manganese Catalysts for Enantioselective Hydrogenation of Ketones.

A series of Mn complexes containing lutidine-based chiral pincer ligands with modular and tunable structures has been developed. The complex shows unprecedentedly high activities (up to 9800 TON; TON=turnover number), broad substrate scope (81 examples), good functional-group tolerance, and excellent enantioselectivities (85-98 % ee) in the hydrogenation of various ketones. These aspects are rare in earth-abundant metal catalyzed hydrogenations.

Ir-SpinPHOX Catalyzed Enantioselective Hydrogenation of 3-Ylidenephthalides.

The first asymmetric hydrogenation of 3-ylidenephthalides has been developed using the Ir complex of a spiro[4,4]-1,6-nonadiene-based phosphine-oxazoline ligand (SpinPHOX) as the catalyst, affording a wide variety of chiral 3-substituted phthalides in excellent enantiomeric excesses (up to 98 % ee). The utility of the protocol has been demonstrated in the asymmetric synthesis of chiral drugs NBP and BZP precursor, as well as the natural products chuangxinol and typhaphthalide.

Chiral Cyclohexyl-Fused Spirobiindanes: Practical Synthesis, Ligand Development, and Asymmetric Catalysis.

1,1'-Spirobiindane has been one type of privileged skeleton for chiral ligand design, and 1,1'-spirobiindane-based chiral ligands have demonstrated outstanding performance in various asymmetric catalysis. However, the access to enantiopure spirobiindane is quite tedious, which obstructs its practical application. In the present article, a facile enantioselective synthesis of cyclohexyl-fused chiral spirobiindanes has been accomplished, in high yields and excellent stereoselectivities (up to >99% ee), via a sequence of Ir-catalyzed asymmetric hydrogenation of α,α'-bis(arylidene)ketones and TiCl promoted asymmetric spiroannulation of the hydrogenated chiral ketones.

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.

Palladium-Catalyzed Asymmetric Allylic Allylation of Racemic Morita-Baylis-Hillman Adducts.

A palladium-catalyzed asymmetric allyl-allyl cross-coupling of acetates of racemic Morita-Baylis-Hillman adducts and allylB(pin) has been developed using a spiroketal-based bis(phosphine) as the chiral ligand, thus affording a series of chiral 1,5-dienes bearing a vinylic ester functionality in good yields, high branched regioselectivities, and uniformly excellent enantioselectivities (95-99 % ee). Further synthetic manipulations of the allylation products provided novel ways for rapid access to a range of chiral polycyclic lactones and polycyclic lactams, as well as the antidepressant drug (-)-Paroxetine, in high optical purities.

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.

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.

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).

Enantiomeric separations of chiral sulfonic and phosphoric acids with barium-doped cyclofructan selectors via an ion interaction mechanism.

New cyclofructan-6 (CF6)-based chiral stationary phases (CSPs) bind barium cations. As a result, the barium-complexed CSPs exhibit enantioselectivity toward 16 chiral phosphoric and sulfonic acids in the polar organic mode (e.g.

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.

Spiro[4,4]-1,6-nonadiene-based diphosphine oxides in lewis base catalyzed asymmetric double-aldol reactions.

Symmetry swap: A C2 -chiral spiro diphosphine oxide (SpinPO) has been found to be highly efficient and enantioselective in the catalysis of double-aldol reactions of ketones and aldehydes to give the corresponding optically active double-aldol products, which can be readily transformed into optically active C3 - and pseudo-C3 -symmetric molecules.

The N-H 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.

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.

Highly enantioselective asymmetric hydrogenation of (E)-β,β-disubstituted α,β-unsaturated Weinreb amides catalyzed by Ir(I) complexes of SpinPhox ligands.

The Ir(I) complexes of chiral spiro phosphino-oxazoline ligands (SpinPhox) have demonstrated good to excellent enantioselectivity in the asymmetric hydrogenation (AH) of a variety of (E)-β,β-disubstituted α,β-unsaturated N-methoxy-N-methylamides, affording the corresponding optically active Weinreb amides with up to 97% ee.