Asymmetric (Transfer) Hydrogenation of Substituted Ketones Through Dynamic Kinetic Resolution

Echeverria, Pierre‐Georges; Ayad, Tahar; Phansavath, Phannarath; Ratovelomanana‐Vidal, Virginie

doi:10.1002/9783527822294.ch5

Cited by 7 publications

(6 citation statements)

References 165 publications

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“…To date, both enantioselective hydrogenations using hydrogen gas and asymmetric transfer hydrogenation have proven to be valuable chemical methods for the enantioselective reduction of ketones . In some cases, several stereogenic centers may be installed when there is an epimerizable chiral center next to the hydride addition site, which allows a dynamic kinetic resolution (DKR) process, demonstrating the versatility of asymmetric (transfer) hydrogenation in synthesizing complex chiral molecules .…”

Section: Asymmetric Transition Metal Catalysismentioning

confidence: 99%

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Yang

Stolarzewicz

et al. 2023

Chem. Rev.

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The proportion of approved chiral drugs and drug candidates under medical studies has surged dramatically over the past two decades. As a consequence, the efficient synthesis of enantiopure pharmaceuticals or their synthetic intermediates poses a profound challenge to medicinal and process chemists. The significant advancement in asymmetric catalysis has provided an effective and reliable solution to this challenge. The successful application of transition metal catalysis, organocatalysis, and biocatalysis to the medicinal and pharmaceutical industries has promoted drug discovery by efficient and precise preparation of enantio-enriched therapeutic agents, and facilitated the industrial production of active pharmaceutical ingredient in an economic and environmentally friendly fashion. The present review summarizes the most recent applications (2008–2022) of asymmetric catalysis in the pharmaceutical industry ranging from process scales to pilot and industrial levels. It also showcases the latest achievements and trends in the asymmetric synthesis of therapeutic agents with state of the art technologies of asymmetric catalysis.

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Section: Asymmetric Transition Metal Catalysismentioning

confidence: 99%

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Yang

Stolarzewicz

et al. 2023

Chem. Rev.

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“…Since the groundbreaking report by Noyori, Ikariya, and co-workers in 1995 using a half-sandwich Ru catalyst, ATH has undergone rapid development . The transformation features high efficiency, low catalyst loading, simple equipment, and safe manipulation and can be scaled up.…”

Section: Introductionmentioning

confidence: 99%

Catalytic Asymmetric Transfer Hydrogenation of Acylboronates: BMIDA as the Privileged Directing Group

Meng,

Lan,

Chen

et al. 2024

J. Am. Chem. Soc.

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Developing a general, highly efficient, and enantioselective catalytic method for the synthesis of chiral alcohols is still a formidable challenge. We report in this article the asymmetric transfer hydrogenation (ATH) of N-methyliminodiacetyl (MIDA) acylboronates as a general substrate-independent entry to enantioenriched secondary alcohols. ATH of acyl-MIDA-boronates with (het)aryl, alkyl, alkynyl, alkenyl, and carbonyl substituents delivers a variety of enantioenriched α-boryl alcohols. The latter are used in a range of stereospecific transformations based on the boron moiety, enabling the synthesis of carbinols with two closely related α-substituents, which cannot be obtained with high enantioselectivities using direct asymmetric hydrogenation methods, such as the (R)-cloperastine intermediate. Computational studies illustrate that the BMIDA group is a privileged enantioselectivity-directing group in Noyori−Ikariya ATH compared to the conventionally used aryl and alkynyl groups due to the favorable CH−O attractive electrostatic interaction between the η 6 -arene-CH of the catalyst and the σ-bonded oxygen atoms in BMIDA. The work expands the domain of conventional ATH and shows its huge potential in addressing challenges in symmetric synthesis.

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“…Dynamic kinetic resolution based on Noyori–Ikariya transfer hydrogenation (DKR-ATH) seemed like a fitting synthetic strategy for addressing the challenging simultaneous control of both chiral centers of the target compound class. − DKR-ATH is a robust method for stereoconvergent access to enantiomerically pure secondary alcohols with multiple contiguous chiral centers starting from the readily available racemic α-substituted ketones, − including fluorinated examples. − This approach to β-CF 3 alcohols would involve in situ epimerization of α-CF 3 ketones via an enol or enolate-anion intermediate. Specifically, α-CF 3 enolates have been associated with decomposition due to fluoride elimination to furnish the corresponding unstable difluoroenone. − This was foreseen as the major obstacle toward an efficient DKR-ATH-based catalytic asymmetric synthesis of β-CF 3 alcohols.…”

Section: Introductionmentioning

confidence: 99%

Catalytic Stereoconvergent Synthesis of Homochiral β-CF₃, β-SCF₃, and β-OCF₃ Benzylic Alcohols

et al. 2022

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We describe an efficient catalytic strategy for enantio- and diastereoselective synthesis of homochiral β-CF3, β-SCF3, and β-OCF3 benzylic alcohols. The approach is based on dynamic kinetic resolution (DKR) with Noyori–Ikariya asymmetric transfer hydrogenation leading to simultaneous construction of two contiguous stereogenic centers with up to 99.9% ee, up to 99.9:0.1 dr, and up to 99% isolated yield. The origin of the stereoselectivity and racemization mechanism of DKR is rationalized by density functional theory calculations. Applicability of the previously inaccessible chiral fluorinated alcohols obtained by this method in two directions is further demonstrated: As building blocks for pharmaceuticals, illustrated by the synthesis of heat shock protein 90 inhibitor with in vitro anticancer activity, and in particular, needle-shaped crystals of representative stereopure products that exhibit either elastic or plastic flexibility, which opens the door to functional materials based on mechanically responsive chiral molecular crystals.

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Asymmetric (Transfer) Hydrogenation of Substituted Ketones Through Dynamic Kinetic Resolution

Cited by 7 publications

References 165 publications

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Catalytic Asymmetric Transfer Hydrogenation of Acylboronates: BMIDA as the Privileged Directing Group

Catalytic Stereoconvergent Synthesis of Homochiral β-CF₃, β-SCF₃, and β-OCF₃ Benzylic Alcohols

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Asymmetric (Transfer) Hydrogenation of Substituted Ketones Through Dynamic Kinetic Resolution

Cited by 7 publications

References 165 publications

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Enantioselective Transformations in the Synthesis of Therapeutic Agents

Catalytic Asymmetric Transfer Hydrogenation of Acylboronates: BMIDA as the Privileged Directing Group

Catalytic Stereoconvergent Synthesis of Homochiral β-CF3, β-SCF3, and β-OCF3 Benzylic Alcohols

Contact Info

Product

Resources

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Catalytic Stereoconvergent Synthesis of Homochiral β-CF₃, β-SCF₃, and β-OCF₃ Benzylic Alcohols