Synergistic Ammonium (Hypo)Iodite/Imine Catalysis for the Asymmetric α-Hydroxylation of β-Ketoesters

Mairhofer, Christopher; Novacek, Johanna; Waser, Mario

doi:10.1021/acs.orglett.0c02198

Cited by 23 publications

(26 citation statements)

References 61 publications

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“…Though enamine-based α-oxygenation has been extensively explored, the successful examples relied on preactivated reagents such as oxaziridines, nitrosobenzenes, benzoyl peroxide and singlet oxygen [22][23][24][25] . Catalytic direct enamine hydroxylation with hydrogen peroxide has not been achieved 26 . Ooi reported an enolate-based asymmetric α-hydroxylation with hydrogen peroxide, unfortunately the reaction required a stoichiometric trichloroacetonitrile as an activating reagent 27 .…”

Section: Introductionmentioning

confidence: 99%

Chiral Primary Amine/Ketone Cooperative Catalysis for Asymmetric α-Hydroxylation with Hydrogen Peroxide

Cai

et al. 2021

J. Am. Chem. Soc.

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Carbonyl and amine are yin and yang in organocatalysis that mutually activate and transform each other. As intrinsically reacting partners, carbonyl and amine tend to condensate, depleting their individual activity when employed as catalysts. Though widely established as prominent catalytic strategies, aminocatalysis and carbonyl catalysis seems not coexist well and a cooperative amine/carbonyl dual catalysis remains virtually unknown. Here we report a cooperative primary amine and ketone dual catalysis in the asymmetric αhydroxylation with H2O2. Besides participating in the typical enamine catalytic cycle, the chiral primary amine catalyst was found to work cooperatively with a ketone catalyst to activate H2O2 via an oxaziridine intermediate derived from in-situ generated ketimine intermediate. The resulted enamine-oxaziridine coupling then facilitated highly-controlled hydroxylation of β-ketocarbonyls that are not possible with other catalytic methods. The dual catalytic approach allows for highly enantioselective α-hydroxylation of a broad range of β-ketocarbonyls. Particularly, late-stage hydroxylation for peptidyl amide or chiral esters can also 2 be achieved with high stereoselectivity. With its operational simplicity and mild conditions, this cooperative amine/ketone catalysis provides a new strategy in catalytic activation of H2O2 and expands the domain of typical amine and carbonyl catalysis to include those challenging transformations.

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Section: Introductionmentioning

confidence: 99%

Chiral Primary Amine/Ketone Cooperative Catalysis for Asymmetric α-Hydroxylation with Hydrogen Peroxide

Cai

et al. 2021

J. Am. Chem. Soc.

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“…Over the last years our group has focused on the stereoselective synthesis of α-hydroxylated and α-fluorinated β-ketoesters 2 and 3 (starting from β-ketoesters 4 ) by using bifunctional chiral quaternary ammonium salt catalysts. 7 , 8 Within these studies, we generally achieved higher enantio-selectivities for the α-hydroxylated products 2 8 than for the α-fluorinated 3 . 7 We thus wondered, if it may be possible to convert the alcohols 2 into organofluorine compounds 3 by means of a stereospecific deoxyfluorination process ( Scheme 1 ).…”

mentioning

confidence: 71%

“… e 100 × ee ( 3a )/ee ( 2a ); absolute configuration was assigned as described previously. 7 , 8 , 12 , 13 …”

Section: Methodsmentioning

confidence: 99%

“…We started our investigations by optimizing the deoxyfluorination of enantioenriched ( S )- 2a (obtained as reported previously 8 ) with DAST ( 1 ), one of the cheapest commercially available established deoxyfluorination agents. 11 As outlined in Table 1 , all reactions were carried out at room temperature using dry CH 2 Cl 2 as the solvent.…”

mentioning

confidence: 99%

“…Absolute configuration of starting material ( S )- 2a and product ( R )- 3a were assigned by comparison of optical rotation and HPLC retention time orders with previous reports. 7 , 8 , 12 , 13 The stereochemical course (inversion or retention of configuration) of DAST-mediated deoxyfluorinations has been a matter of discussion 4 , 5 and mostly depends on the nature of the substrate. For our target transformation the observed inversion suggests a clean S N 2-type mechanism 14 and as can be seen from all the results summarized in Table 1 , the observed levels of enantiospecificity were always satisfying (see Scheme 2 for the proposed mechanistic scenario).…”

mentioning

confidence: 99%

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