Biomimetic Asymmetric Reduction of Tetrasubstituted Olefin 2,3-Disubstituted Inden-1-ones with Chiral and Regenerable NAD(P)H Model CYNAM

Because of the formidable development of the asymmetric reduction of tetrasubstituted olefins, an effective method is in urgent demand. Herein, through the biomimetic protocol of the coenzyme NAD­(P)­H, the reduction of tetrasubstituted olefin 2,3-substituted 1H-inden-1-ones has been successfully realized with the catalytic chiral NAD­(P)H model CYNAM, which is hard to bring about via the common rhodium or iridium-based catalytic system, producing the corresponding products in good yield (up to 98%) with good enantioselectivity (up to 99% ee). Furthermore, the chiral bioactive molecule can be concisely synthesized from the reduced product

Asymmetric Transfer Hydrogenation of 2,3-Disubstituted Flavanones through Dynamic Kinetic Resolution Enabled by Retro-Oxa-Michael Addition: Construction of Three Contiguous Stereogenic Centers

A ruthenium-catalyzed asymmetric transfer hydrogenation of 2,3-disubstituted flavanones was developed for the construction of three contiguous stereocenters under basic conditions through a combination of dynamic kinetic resolution and retro-oxa-Michael addition, giving chiral flavanols with excellent enantioselectivities and diastereoselectivities. The reaction proceeded via a base-catalyzed retro-oxa-Michael addition to racemize two stereogenic centers simultaneously in concert with a highly enantioselective ketone transfer hydrogenation step. The asymmetric transfer hydrogenation could be achieved at gram scale without loss of the activity and enantioselectivity

Enantioselective Synthesis of 2‑Functionalized Tetrahydroquinolines through Biomimetic Reduction

Biomimetic asymmetric reduction of 2-functionalized quinolines has been successfully developed with the chiral and regenerable NAD­(P)­H model CYNAM in the presence of transfer catalyst simple achiral phosphoric acids, providing the chiral 2-functionalized tetrahydroquinolines with up to 99% ee. Using this methodology as a key step, a chiral and potent opioid analgesic containing a 1,2,3,4-tetrahydroquinoline motif was synthesized with high overall yield

Chiral and Regenerable NAD(P)H Models Enabled Biomimetic Asymmetric Reduction: Design, Synthesis, Scope, and Mechanistic Studies

The coenzyme NAD­(P)H plays an important role in electron as well as proton transmission in the cell. Thus, a variety of NAD­(P)H models have been involved in biomimetic reduction, such as stoichiometric Hantzsch esters and achiral regenerable dihydrophenantheridine. However, the development of a general and new-generation biomimetic asymmetric reduction is still a long-term challenge. Herein, a series of chiral and regenerable NAD­(P)H models with central, axial, and planar chiralities have been designed and applied in biomimetic asymmetric reduction using hydrogen gas as a terminal reductant. Combining chiral NAD­(P)­H models with achiral transfer catalysts such as Brønsted acids and Lewis acids, the substrate scope could be also expanded to imines, heteroaromatics, and electron-deficient tetrasubstituted alkenes with up to 99% yield and 99% enantiomeric excess (ee). The mechanism of chiral regenerable NAD­(P)H models was investigated as well. Isotope-labeling reactions indicated that chiral NAD­(P)H models were regenerated by the ruthenium complex under hydrogen gas first, and then the hydride of NAD­(P)H models was transferred to unsaturated bonds in the presence of transfer catalysts. In addition, density functional theory calculations were also carried out to give further insight into the transition states for the corresponding transfer catalysts

Chiral and Regenerable NAD(P)H Models Enabled Biomimetic Asymmetric Reduction: Design, Synthesis, Scope, and Mechanistic Studies

The coenzyme NAD­(P)H plays an important role in electron as well as proton transmission in the cell. Thus, a variety of NAD­(P)H models have been involved in biomimetic reduction, such as stoichiometric Hantzsch esters and achiral regenerable dihydrophenantheridine. However, the development of a general and new-generation biomimetic asymmetric reduction is still a long-term challenge. Herein, a series of chiral and regenerable NAD­(P)H models with central, axial, and planar chiralities have been designed and applied in biomimetic asymmetric reduction using hydrogen gas as a terminal reductant. Combining chiral NAD­(P)­H models with achiral transfer catalysts such as Brønsted acids and Lewis acids, the substrate scope could be also expanded to imines, heteroaromatics, and electron-deficient tetrasubstituted alkenes with up to 99% yield and 99% enantiomeric excess (ee). The mechanism of chiral regenerable NAD­(P)H models was investigated as well. Isotope-labeling reactions indicated that chiral NAD­(P)H models were regenerated by the ruthenium complex under hydrogen gas first, and then the hydride of NAD­(P)H models was transferred to unsaturated bonds in the presence of transfer catalysts. In addition, density functional theory calculations were also carried out to give further insight into the transition states for the corresponding transfer catalysts

Chiral and Regenerable NAD(P)H Models Enabled Biomimetic Asymmetric Reduction: Design, Synthesis, Scope, and Mechanistic Studies

The coenzyme NAD­(P)H plays an important role in electron as well as proton transmission in the cell. Thus, a variety of NAD­(P)H models have been involved in biomimetic reduction, such as stoichiometric Hantzsch esters and achiral regenerable dihydrophenantheridine. However, the development of a general and new-generation biomimetic asymmetric reduction is still a long-term challenge. Herein, a series of chiral and regenerable NAD­(P)H models with central, axial, and planar chiralities have been designed and applied in biomimetic asymmetric reduction using hydrogen gas as a terminal reductant. Combining chiral NAD­(P)­H models with achiral transfer catalysts such as Brønsted acids and Lewis acids, the substrate scope could be also expanded to imines, heteroaromatics, and electron-deficient tetrasubstituted alkenes with up to 99% yield and 99% enantiomeric excess (ee). The mechanism of chiral regenerable NAD­(P)H models was investigated as well. Isotope-labeling reactions indicated that chiral NAD­(P)H models were regenerated by the ruthenium complex under hydrogen gas first, and then the hydride of NAD­(P)H models was transferred to unsaturated bonds in the presence of transfer catalysts. In addition, density functional theory calculations were also carried out to give further insight into the transition states for the corresponding transfer catalysts