Highly Enantioselective Hydrogenation of Unsymmetrical Benzophenones via Iridium-f-phamidol Catalysis.

A sequence of f-phamidol-based tetradentate phosphine ligands have been developed and successfully used in iridium-catalyzed enantioselective hydrogenation of benzophenones to deliver chiral benzhydrols in almost quantitative yields and with excellent enantioselectivities (up to >99% yield and up to >99% ee). Moreover, the catalytic system shows a broad substrate scope and functional group tolerance. The synthetic utilities of this methodology have been showcased by gram-scale experiments and the formal synthesis of levocetirizine.

Isomerization reactions of metal vinylidene units.

Isomerization reactions of unsaturated molecules offer an efficient strategy in atom-economical synthesis. Although isomerization reactions of unsaturated organic and organometallic compounds, such as alkenes, alkynes, and metal carbynes, have been achieved, those of metal vinylidene units that contain cumulated double bonds have never been reported. Herein, we inaugurally discovered isomerization reactions of metal vinylidene units via protonation and deprotonation reactions of metal carbenes. Experimental and theoretical investigations indicate that the electrical characteristics of substituents on the rings play a crucial role in controlling the formation of metal vinylidene units. The isomerization reactions of metal vinylidene units were driven by thermodynamic forces. Moreover, one of the angles at metal vinylidenes was found as 126.9°, representing the smallest angle in metal vinylidenes and the first cyclic 4d transition metal (Ru) vinylidene complex was successfully isolated. These investigations unveil novel structures and reactivity for metal vinylidenes, offering a fresh perspective on the isomerization reactions of unsaturated molecules containing cumulative unsaturated bonds.

A 13-million turnover-number anionic Ir-catalyst for a selective industrial route to chiral nicotine.

Developing catalysts with both useful enantioselectivities and million turnover numbers (TONs) for asymmetric hydrogenation of ketones is attractive for industrial production of high-value bioactive chiral entities but remains a challenging. Herein, we report an ultra-efficient anionic Ir-catalyst integrated with the concept of multidentate ligation for asymmetric hydrogenation of ketones. Biocatalysis-like efficacy of up to 99% ee (enantiomeric excess), 13,425,000 TON (turnover number) and 224 s-1 TOF (turnover frequency) were documented for benchmark acetophenone. Up to 1,000,000 TON and 99% ee were achieved for challenging pyridyl alkyl ketone where at most 10,000 TONs are previously reported. The anionic Ir-catalyst showed a novel preferred ONa/MH instead of NNa/MH bifunctional mechanism. A selective industrial route to enantiopure nicotine has been established using this anionic Ir-catalyst for the key asymmetric hydrogenation step at 500 kg batch scale, providing 40 tons scale of product.

Concise Synthesis of Chiral Tricyclic Lactams by Tandem Dynamic Kinetic Asymmetric Reductive Amination/Lactamization Using Ammonium Salts.

The atom- and step-efficient synthesis of chiral fused tricyclic lactams from readily available ketoesters using cheap ammonium salts as the nitrogen source is reported. This ruthenium-catalyzed system operates through an efficient tandem dynamic kinetic asymmetric reductive amination (ARA)/lactamization and produces chiral fused tricyclic lactams in high yields with excellent diastereo- and enantioselectivity (up to >99 % ee, >20 : 1 dr and 98 % yield). The robust method was also applied to the concise synthesis of key intermediates in the synthesis of rivastigmine analogues and chiral N-heterocyclic carbene catalysts.

One-Pot Synthesis of High-Strained Metal Vinylidene and Metal Carbyne.

A novel one-pot reaction producing a metal vinylidene structure in a five-membered ring by cyclization of a multiyne has been achieved. The ring strain and the high stability of the cyclic metal vinylidene complexes have been analyzed experimentally and computationally. The metal vinylidene unit in a fused-ring complex is unreactive to both nucleophiles and electrophiles. It reacts however at the nearby carbonyl group achieving the unprecedented conversion of metal tributing factors for the aromaticity-driven process has been studied by DFT calculations.

Asymmetric hydrogenation of 1,4-diketones: facile synthesis of enantiopure 1,4-diarylbutane-1,4-diols.

Owing to the biological significance and great synthetic value of 1,4-diarylbutane-1,4-diols and their derivatives, increasingly considerable attention has been paid to developing effective synthetic methods for chiral 1,4-diarylbutane-1,4-diols. We herein report an efficient asymmetric hydrogenation of 1,4-diaryldiketones catalyzed by a chiral iridium complex bearing f-amphox as ligand, furnishing a series of 1,4-diarylbutane-1,4-diols in excellent yields (up to >99%) with exceptional enantioselectivities (up to >99.9% ee) and diastereoselectivities (up to >100 : 1 dr).

Extension of the Simmons-Smith reaction to metal-carbynes: efficient synthesis of metallacyclopropenes with σ-aromaticity.

The Simmons-Smith reaction offers a direct route for conversion of an alkene into a cyclopropane with a zinc carbenoid as the active intermediate. Zinc carbenoids, however, have never delivered a methylene unit to substrates with metal-carbon multiple bonds. Herein, we describe this type of reaction and the construction of three-membered rings has now been applied in organometallic systems by combining classical zinc carbenoid reagents with a range of structurally and electronically diverse metal carbynes. A variety of metallacyclopropene derivatives prepared in this way represent rare examples with σ-aromaticity in an unsaturated three-membered ring. The structures of such products are supported by experimental observations and theoretical calculations.

A missing member of conjugated N-heterocycles: realizing pyrido[1,2-α]azepine by reacting ruthenium alkenylcarbene complex with alkyne.

Despite the excellent chemical properties of N-heterocycles, pyrido[1,2-α]azepine remains elusive due to its potential antiaromaticity and lability. Herein, we demonstrate the synthesis and characterization of the first bicyclic pyrido[1,2-α]azepine that leverages the coordination to the ruthenium center to promote the stability of N-bridged bicycle.