Asymmetric Transfer Hydrogenation of <i>gem</i>‐Difluorocyclopropenyl Esters: Access to Enantioenriched <i>gem</i>‐Difluorocyclopropanes

Yamani, Khalil; Pierre, Hugo; Archambeau, Alexis; Meyer, Christophe; Cossy, Janine

doi:10.1002/ange.202008572

Cited by 8 publications

(6 citation statements)

References 73 publications

(36 reference statements)

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“…Commercially available Noyori‐Ikariya complex 59 enabled the enantioselective reduction of several gem ‐difluorocyclopropenyl esters 62 in 58–85 % yield and 66–99 % ee with i ‐PrOH as the reducing agent (Figure 24). [108] …”

Section: Transition‐metal‐catalyzed Acrmentioning

confidence: 99%

Catalytic Asymmetric Conjugate Reduction

et al. 2023

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Enantioselective reduction reactions are privileged transformations for the construction of trisubstituted stereogenic centers. While these include established synthetic strategies, such as asymmetric hydrogenation, methods based on the enantioselective addition of hydridic reagents to electrophilic prochiral substrates have also gained importance. In this context, the asymmetric conjugate reduction (ACR) of α,β-unsaturated compounds has become a convenient approach for the synthesis of chiral compounds with trisubstituted stereocenters in α-, β-, or γ-position to electron-withdrawing functional groups. Because such activating groups are diverse and amenable of further derivatizations, ACRs provide a general and powerful synthetic entry towards a variety of valuable chiral building blocks. This Review provides a comprehensive collection of catalytic ACR methods involving transition-metal, organic, and enzymatic catalysis since its first versions dating back to the late 1970s.

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Section: Transition‐metal‐catalyzed Acrmentioning

confidence: 99%

Catalytic Asymmetric Conjugate Reduction

et al. 2023

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“…Although the chemo‐enzymatic reaction as mentioned before [12,21,31,33–39] or classical optical resolution [30] have been the only means to synthesize chiral gem ‐difluorocyclopropanes for a long time, two examples of the asymmetric synthesis of gem ‐difluorocyclopropanes have been recently developed [43–45] . Cossy et al.…”

Section: Synthesis Of Chiral Gem‐difluorocyclopropanes Via Chemo‐enzy...mentioning

confidence: 99%

“…Cossy et al. accomplished the synthesis of a gem ‐difluorocyclopropane via the asymmetric hydration of cylclopropene using a chiral Rh complex [43] . Sekine and co‐workers also reported the successful synthesis of chiral gem ‐difluorocyclopropanes and by the similar methodology using a different chiral catalyst [44,45] .…”

Section: Synthesis Of Chiral Gem‐difluorocyclopropanes Via Chemo‐enzy...mentioning

confidence: 99%

Synthesis of Selectively gem‐Difluorinated Molecules; Chiral gem‐Difluorocyclopropanes via Chemo‐Enzymatic Reaction and gem‐Difluorinated Compounds via Radical Reaction

Itoh

Hayase

Nokami

2023

The Chemical Record

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The incorporation of fluorine atoms into an organic compound can alter the chemical reactivity or biological activity of the resulting compound due to the strong electron withdrawing nature of the fluorine atom. We have synthesized many original gem‐difluorinated compounds and described the results in four sections. The first section describes the synthesis of optically active‐gem‐difluorocyclopropanes via the chemo‐enzymatic reaction; we applied these compounds to liquid crystalline molecules, then further discovered a potent DNA cleavage activity for the gem‐difluorocyclopropane derivatives. The second section describes the synthesis of selectively gem‐difluorinated compounds via a radical reaction; we synthesized fluorinated analogues of a sex pheromone of the male African sugarcane borer, Eldana saccharina, and used the compounds as proof for investigating the origin of pheromone molecule recognition on the receptor protein. The third involves the synthesis of 2,2‐difluorinated‐esters by visible light‐driven radical addition of 2,2‐difluoroacetate with alkenes or alkynes in the presence of an organic pigment. The last section describes the synthesis of gem‐difluorinated compounds via the ring‐opening of gem‐difluorocyclopropanes. We further developed a novel method of synthesizing gem‐difluorohomoallylic alcohols via the ring‐opening of gem‐difluorocyclopropane and aerobic oxidation by photo‐irradiation in the presence of an organic pigment. Since gem‐difluorinated compounds that were prepared by the present method have two olefinic moieties with a different reactivity at the terminal position, we accomplished the synthesis of four types of gem‐difluorinated cyclic alkenols via the ring‐closing‐metathesis (RCM) reaction.

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“…Almost at the same time, Cossy and co-workers developed an asymmetric transfer hydrogenation of gem-difluorocyclopropenyl esters with isopropanol as the hydrogen donor that was catalyzed by a Noyori-Ikariya catalyst [( p-cymene)-ruthenium(II) complex with N-tosyl-1,2-diphenylethylenediamine as the chiral ligand] with moderate to high enantioselectivity (66-99% ee). 17 Therefore, the development of an enantioselective transitionmetal-catalyzed functionalization of unsymmetric difluorocyclopropenes is really a formidable endeavour, particularly in the enantioselective synthesis of densely polysubstituted difluorocyclopropanes. Herein, we report a highly chemo-, regio-and stereoselective functionalization of unsymmetric difluorocyclopropenes with various silyl metal intermediates under mild reaction conditions with the aid of transition metal catalysis (Fig.…”

Section: Introductionmentioning

confidence: 99%