Catalytic Asymmetric Oxidative γ‐Coupling of α,β‐Unsaturated Aldehydes with Air as the Terminal Oxidant

Næsborg, Line; Corti, Vasco; Leth, Lars A.; Poulsen, Pernille; Jørgensen, Karl Anker

doi:10.1002/ange.201711944

Cited by 17 publications

(4 citation statements)

References 48 publications

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“…Inspired by our previous findings, we envisioned the feasibility of the α,β -desaturation initiated γ -functionalization of aliphatic ketones with nucleophilic amines that was expected to take place through α,β -desaturation of ketone to enone intermediate, subsequent oxidation of γ -C(sp 3 )–H bond of enone to form electrophilic species, final capture of the resulting electrophilic species with amine to form C–N bond at the position γ to carbonyl group. This targeted dehydrogenative ketone γ -amination is challenging to access because the electron-withdrawing carbonyl disfavors the oxidation of enone γ -C(sp 3 )–H bond to generate electrophilic species 58 , mechanistically contrasting with the previously reported secondary amine-catalyzed γ -functionalization of enal that is, in principle, the dehydrogenative cross-coupling of enal with electrophilic reagent via deprotonation of γ -C(sp 3 )–H in the iminum intermediate of enal to form nucleophilic species 51,52,54,59,60 .…”

Section: Introductionmentioning

confidence: 99%

Copper-catalyzed dehydrogenative γ-C(sp3)-H amination of saturated ketones for synthesis of polysubstituted anilines

Chen

Zhang

et al. 2019

Nat Commun

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Metal-catalyzed β -C-H functionalization of saturated carbonyls via dehydrogenative desaturation proved to be a powerful tool for simplifying synthesis of valuable β -substituted carbonyls. Here, we report a copper-catalyzed dehydrogenative γ -C(sp 3 )-H amination of saturated ketones that initiates the three-component coupling of saturated ketones, amines and N -substituted maleimides to construct polysubstituted anilines. The protocol presented herein enables both linear and α -branched butanones to couple a wide spectrum of amines and various N -substituted maleimides to produce diverse tetra- or penta-substituted anilines in fair-to-excellent yields with good functional group tolerance. The mechanism studies support that this ketone dehydrogenative γ -C(sp 3 )-H amination was triggered by the ketone α,β -dehydrogenation desaturation that activates the adjacent γ -C(sp 3 )-H bond towards functionalization. This α,β -dehydrogenation desaturation-triggered cascade sequence opens up a new avenue to the remote C(sp 3 )-H functionalization of saturated ketones and has the potential to enable the rapid syntheses of complex compounds from simple starting materials.

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Section: Introductionmentioning

confidence: 99%

Copper-catalyzed dehydrogenative γ-C(sp3)-H amination of saturated ketones for synthesis of polysubstituted anilines

Chen

Zhang

et al. 2019

Nat Commun

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“…52 In 2018, Jørgensen and co-workers reported an intriguing oxidative γ-coupling of α,β-unsaturated aldehydes by chiral amine/copper combined catalysis under aerobic conditions. 53 The reaction was proposed to proceed via coupling with the dienamine radical cation intermediate Int-25. This reaction is so far limited to homo-and heterocoupling of α,β-unsaturated aldehydes, and it remains to be seen whether the scope could be enlarged to include coupling with other nucleophiles (Scheme 25).…”

Section: Of Aldehydes (Scheme 19)mentioning

confidence: 99%

Catalytic Asymmetric Oxidative Enamine Transformations

et al. 2018

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Enamine catalysis is a prevalent strategy for the functionalization of aldehydes/ketones with electrophiles. Recently, the advent and development of oxidative enamine catalysis have allowed for the coupling of enamines with readily available nucleophiles under oxidative conditions, significantly expanding the domain of typical enamine catalysis. In this perspective, we summarize the recent advances in asymmetric oxidative enamine catalysis. On the basis of the oxidative strategy, these could be classified as (1) oxidation of nucleophile, (2) oxidation of enamine via single-electron transfer (SOMO catalysis), and (3) oxidation of enamine to α,β-unsaturated iminium ion, i.e. oxidative iminium catalysis. These strategies have enabled efficient oxidative functionalizations of aldehydes/ketones with various O-, N-, and C-centered nucleophiles in a highly stereocontrolled manner.

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“…More recently and following their initial finding, 39 Jørgensen reported an oxidative homocoupling of aldehydes 2.1.27. 40 Using silver carbonate as oxidant, proline derived enamine is oxidized to afford a radical cation 2.1.27A.…”

Section: Scheme 11 Examples Of Different Alkylation Of Aldehydes Sche...mentioning

confidence: 77%

Enantioselective Radical Reactions Using Chiral Catalysts

Mondal¹,

et al. 2022

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Scheme 24 Enantioselective Radical Hydroacylation of Enals with α-Ketoacids byMerging Photoredox Catalysis with Amine Catalysis.Jang et al. exploited enantioselective tandem Michael addition/oxyamination of α,β-unsaturated aldehydes by combining asymmetric iminium catalysis using organocatalyst with photoinduced SOMO catalysis using N719/TiO2. 60 Here, TiO2 acts as a second cooperative photocatalyst along with Ru photocatalyst N719 which bound to the latter, increases the enantio-and diastereoselectivity of the process. Adamantane carboxylic acid (30 mol%) was used as an additive which promotes formation of iminium ion 2.1.48A from aldehyde 2.1.48 and chiral amine catalyst. This iminium intermediate then reacts with diethyl malonate to provide intermediate 2.1.48B which either undergoes hydrolysis to form β-substituted aldehyde 2.1.50 or photo-oxidation by the photoexcited Ru(II) dye to form enamine radical 2.1.48C. Subsequent addition of TEMPO to radical intermediate 2.1.48BC followed by hydrolysis afforded the desired product 2.1.49 (Scheme 25). This mechanism is obeying to a polar/radical crossover sequence where the first stereocontrol arises from the addition of the malonate.Recently, Bach group reported promising preliminary results of enantioselective [2+2] photocycloaddition of cinnamaldehyde in the presence of ruthenium photocatalyst and proline derived organocatalyst. 61

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Catalytic Asymmetric Oxidative γ‐Coupling of α,β‐Unsaturated Aldehydes with Air as the Terminal Oxidant

Cited by 17 publications

References 48 publications

Copper-catalyzed dehydrogenative γ-C(sp3)-H amination of saturated ketones for synthesis of polysubstituted anilines

Copper-catalyzed dehydrogenative γ-C(sp3)-H amination of saturated ketones for synthesis of polysubstituted anilines

Catalytic Asymmetric Oxidative Enamine Transformations

Enantioselective Radical Reactions Using Chiral Catalysts

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