Facile Synthesis of Enantiopure Sugar Alcohols: Asymmetric Hydrogenation and Dynamic Kinetic Resolution Combined.

An unprecedented Ir/f-amphox-catalyzed asymmetric hydrogenation of racemic 2,3-syn-dihydroxy-1,4-diones is presented involving dynamic kinetic resolution, which produces (1R,2R,3R,4R)-tetraols. This protocol constitutes an efficient and straightforward approach to accessing sugar alcohols bearing four contiguous stereocenters. The strategy exhibits various advantages over existing methods, including excellent yields (up to 98 %), exceptional stereoselectivities (up to 99:1 dr, 99.9 % ee), operational simplicity and substrate generality. Moreover, the nature of the reaction was revealed as a stepwise transformation by in situ Fourier-transform infrared spectroscopy and isolation of intermediates.

A new class of tunable dendritic diphosphine ligands: synthesis and applications in the Ru-catalyzed asymmetric hydrogenation of functionalized ketones.

A series of tunable G0-G3 dendritic 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) ligands was prepared by attaching polyaryl ether dendrons onto the four phenyl rings on the P atoms. Their ruthenium complexes were employed in the asymmetric hydrogenation of ß-ketoesters, α-ketoesters, and α-ketoamides to reveal the effects of dendron size on the catalytic properties. The second- and third-generation catalysts exhibited excellent enantioselectivities, which are remarkably higher than those obtained from the small molecular catalysts and the first-generation catalyst. Molecular modeling indicates that the incorporation of bulky dendritic wedges can influence the steric environments around the metal center. In addition, the ruthenium catalyst bearing a second-generation dendritic ligand could be recycled and reused seven times without any obvious decrease in enantioselectivity.

Development of a One-Step Synthesis of oxa-Spirocyclic Diphosphine Ligands Driven by Their Application in the Industrial Synthesis of Sacubitril.

Herein we have developed a highly practical and efficient one-step coupling protocol for the synthesis of chiral spiro diphosphine ligands, especially for the oxa-spiro diphosphine ligands O-SDP, which showed excellent reactivity and diastereoselectivity in the asymmetric hydrogenation of a key intermediate of Sacubitril. It should be noted that the one-step coupling protocol could be operated on a kilogram scale, and the resulting ruthenium catalyst of O-SDP could hydrogenate the key intermediate of Sacubitril on an industrial scale.

Stereodivergent Synthesis of Enantioenriched 2-Pyrrolidones via Diastereoselective Hydrogenation of α,ß-Unsaturated γ-Lactams.

Synthesis of optically enriched racetam analogues was achieved via highly remote diastereocontrolled and enantiocontrolled Pd/C-catalyzed hydrogenation of α,ß-unsaturated γ-lactams. Various mono- and disubstituted 2-pyrrolidones were obtained in excellent yields and stereoselectivities, and a concise and large-scale synthesis of brivaracetam was developed from inexpensive l-2-aminobutyric acid. Surprisingly, stereodivergent hydrogenation was observed by modifying remote functionalized stereocenters and additives, which would provide alternative stereochemical options of chiral racetams synthesis.

Dendron-containing tetraphenylethylene compounds: dependence of fluorescence and photocyclization reactivity on the dendron generation.

The synthesis and characterization of four dendron-containing tetraphenylethylenes (TPEs), 1(1)-1(4), were synthesized, along with a TPE compound that contained four OCH(2) Ph groups (referred to as 1(0)) for comparison. Photophysical studies revealed that the TPE core became emissive after linking dendrons onto its periphery. Moreover, the fluorescence intensity was significantly enhanced when high-generation dendrons were linked onto the TPE core; the fluorescence intensity increased in the following order: 1(1)<1(2)<1(3)<1(4). This phenomenon was tentatively attributed to an enhancement in the energy barrier for internal rotation and torsion of the TPE core to which four dendrons were connected. In addition, the photocyclization of the TPE core into the respective 9,10-diphenylphenanthrene was facilitated when high-generation dendrons were linked to the TPE core. Again, the photocycliztion reactivity increased in the following order: 1(1)<1(2)<1(3)<1(4). We found that the fluorescence and photocyclization reactivity of TPE could be modulated by covalent interactions with dendrons, and such modulation was strongly dependent on the dendron-generation.

Highly efficient and enantioselective synthesis of ß-heteroaryl amino alcohols via Ru-catalyzed asymmetric hydrogenation.

Chiral ß-heteroaryl amino alcohols are key fragments of many bioactive compounds and antibiotics, and the development of efficient synthetic methods for these compounds is of great value. The highly enantioselective hydrogenation of α-N-heteroaryl ketones was realized with a ruthenium-diphosphine-diamine catalyst, providing the corresponding chiral ß-heteroaryl amino alcohols with up to 99% yield and up to >99% ee. The synthetic utilities of the current reaction were demonstrated by gram-scale synthesis of key intermediates of Sertaconazole and Cenobamate.

Highly enantioselective hydrogenation of 2,4-diaryl-1,5-benzodiazepines catalyzed by dendritic phosphinooxazoline iridium complexes.

A PHOX with arms: A series of dendrimers with Ir phosphinooxazoline (PHOX) cores were designed and synthesized and found to be highly effective and recoverable catalysts for asymmetric hydrogenation of 2,4-diaryl-1,5-benzodiazepines. An obvious positive dendritic effect on reactivity was observed, leading to chiral nitrogen-containing heterocycles with excellent enantioselectivities.