Catalytic Asymmetric Synthesis of α,α-Difluoromethylated and α-Fluoromethylated Tertiary Alcohols

Huang, Wei‐Sheng; Delcourt, Marie-Léonie; Pannecoucke, Xavier; Charette, André B.; Poisson, Thomas; Jubault, Philippe

doi:10.1021/acs.orglett.9b02792

Cited by 11 publications

(6 citation statements)

References 54 publications

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“…1,1-Disubstituted alkenes are a particularly challenging class of substrates in enantioselective catalysis. [34] Along similar lines, Poisson and Jubault later showed [35] that the corresponding difluoromethyl-and monofluoromethyl-substituted alkenes, represented by 21 (Scheme 7b) and generated from the corresponding purchasable ketone (e.g., 20), can be used with similar efficiency and selectivity ( 19 b-c). Two years earlier, Charette and Jubault [36] had disclosed that α-difluoromethyl-substituted styrenes can be transformed to densely functionalized cyclopropanes through processes catalyzed by a chiral di-Rh complex (e.g., 22, Scheme 7b).…”

Section: Fluoromethyl Ketones As Precursors To α-Fluoromethyl Styrene...mentioning

confidence: 93%

Catalytic and Stereoselective Transformations with Easily Accessible and Purchasable Allyl and Alkenyl Fluorides

Paioti

Gonsales

et al. 2022

Angew Chem Int Ed

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Stereochemically defined organofluorine compounds are vital to drug discovery and many applicable catalytic strategies have been introduced for accessing these entities stereoselectively. One approach entails incorporation of a fluorine atom (CÀ F bond formation) or an organofluorine moiety (e.g., CF 3 or CF 2 H), and another exploits commercially available compounds with one or more fluorine atoms. Here, we present the state-of-the-art regarding the use of alkenyl and allylic fluorides in preparation of stereochemically defined fluoro-organic molecules. Allylic and alkenyl fluorides may be purchased or generated from a commercially available acid, carboxylate salt, ester, aldehyde hydrate, or ketone bearing several fluorine atoms next to a carbonyl group. We underscore the untapped potential of purchasable organofluorine compounds, many allylic and alkenyl fluorides, as launching points for development of stereoselective processes that are of value to therapeutic science."In sciences like chemistry, …experience demonstrates at every step that the work of the past has availed much, and that, without it, it would be impossible to advance 'into the ocean of the unknown.' We are compelled to value their history … and to engage in a work which not only gives mental satisfaction but is also useful."

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Section: Fluoromethyl Ketones As Precursors To α-Fluoromethyl Styrene...mentioning

confidence: 93%

Catalytic and Stereoselective Transformations with Easily Accessible and Purchasable Allyl and Alkenyl Fluorides

Paioti

Gonsales

et al. 2022

Angew Chem Int Ed

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“…Hence, as part of our ongoing research program dedicated to electrosynthesis and organofluorine chemistry, we sought to develop a versatile methodology for accessing difluoromethylated building blocks of interest. Taking advantage of the versatile reactivity of alkenes, we suggested a possible addition of an electrogenerated CF 2 H radical on electron-rich alkenes .…”

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confidence: 99%

Electrochemical Difluoromethylation of Electron-Rich Olefins

2023

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The electrochemical difluoromethylation of electron-rich olefins (enamides and styrene derivatives) is disclosed. The addition of the electrogenerated difluoromethyl radical from the corresponding sodium sulfinate (i.e., HCF2SO2Na) to enamides and styrenes in an undivided cell allowed the formation of a large panel of difluoromethylated building blocks in good to excellent yields (42 examples, 23–87% yields). A plausible unified mechanism was suggested according to control experiments and cyclic voltammetry measurements.

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“…The resulting diols syn - 3 are valuable motifs in medicinal chemistry, − but the literature reports on their asymmetric synthesis are limited to a few sporadic examples. Stereoselective synthesis of syn- 3a (98% ee) was achieved via Sharpless dihydroxylation .…”

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confidence: 99%

Hydrogen-Bonding Ability of Noyori–Ikariya Catalysts Enables Stereoselective Access to CF₃-Substituted syn-1,2-Diols via Dynamic Kinetic Resolution

et al. 2023

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Stereopure CF3-substituted syn-1,2-diols were prepared via the reductive dynamic kinetic resolution of the corresponding racemic α-hydroxyketones in HCO2H/Et3N. (Het)aryl, benzyl, vinyl, and alkyl ketones are tolerated, delivering products with ≥95% ee and ≥87:13 syn/anti. This methodology offers rapid access to stereopure bioactive molecules. Furthermore, DFT calculations for three types of Noyori–Ikariya ruthenium catalysts were performed to show their general ability of directing stereoselectivity via the hydrogen bond acceptor SO2 region and CH/π interactions.

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Catalytic Asymmetric Synthesis of α,α-Difluoromethylated and α-Fluoromethylated Tertiary Alcohols

Cited by 11 publications

References 54 publications

Catalytic and Stereoselective Transformations with Easily Accessible and Purchasable Allyl and Alkenyl Fluorides

Catalytic and Stereoselective Transformations with Easily Accessible and Purchasable Allyl and Alkenyl Fluorides

Electrochemical Difluoromethylation of Electron-Rich Olefins

Hydrogen-Bonding Ability of Noyori–Ikariya Catalysts Enables Stereoselective Access to CF₃-Substituted syn-1,2-Diols via Dynamic Kinetic Resolution

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Catalytic Asymmetric Synthesis of α,α-Difluoromethylated and α-Fluoromethylated Tertiary Alcohols

Cited by 11 publications

References 54 publications

Catalytic and Stereoselective Transformations with Easily Accessible and Purchasable Allyl and Alkenyl Fluorides

Catalytic and Stereoselective Transformations with Easily Accessible and Purchasable Allyl and Alkenyl Fluorides

Electrochemical Difluoromethylation of Electron-Rich Olefins

Hydrogen-Bonding Ability of Noyori–Ikariya Catalysts Enables Stereoselective Access to CF3-Substituted syn-1,2-Diols via Dynamic Kinetic Resolution

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Hydrogen-Bonding Ability of Noyori–Ikariya Catalysts Enables Stereoselective Access to CF₃-Substituted syn-1,2-Diols via Dynamic Kinetic Resolution