Highly Enantioselective Carbonyl–Ene Reactions of 2,3‐Diketoesters: Efficient and Atom‐Economical Process to Functionalized Chiral α‐Hydroxy‐β‐Ketoesters

Truong, Phong; Zavalij, Peter Y.; Doyle, Michael P.

doi:10.1002/ange.201402233

Cited by 16 publications

(9 citation statements)

References 57 publications

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“…It was found β-ketoamides worked extremely well under our dual catalytic conditions. Both aryl and alkyl amides could be incorporated to give the expected hydroxylation adducts with 93-99% ee (entries[25][26][27][28][29][30][31][32]. Aryl amides bearing either electrondonating group (6b), electron-withdrawing groups (6c-e) or streric ortho-substituent (6g) were equally applicable.…”

mentioning

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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mentioning

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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“…Convenient access to α-diazo-β-ketoesters and the replacement of dinitrogen by oxygen have provided a significant expansion of the carbonyl-ene reaction through uses of 2,3-diketoesters as enophiles [138]. With chiral copper(II) box as the catalyst, high enantioselectivities are achieved under very mild conditions (Scheme 32).…”

Section: [2+2] Cycloaddition Reactionsmentioning

confidence: 98%

“…Scheme 29 Enantioselective carbonyl-ene reaction of trifluoropyruvate [132] Scheme 30 Enantioselective carbonyl-ene reaction on BINOLate/titanium catalyst encapsulated in magnetic nanoreactors [133] Scheme 31 Enantioselective cationic polyene cyclization of α-ketoester [137] Scheme 32 Highly enantioselective carbonyl-ene reactions of 2,3-diketoesters [138] Q. Sha et al With the substituent R being a broad spectrum of structures and functional groups, the potential of these enophiles to broaden the applicability of the carbonyl-ene reaction in organic synthesis is high.…”

Section: Scheme 28mentioning

confidence: 99%

The Future of Catalysis by Chiral Lewis Acids

Sha

Deng

Doyle

2015

Topics in Organometallic Chemistry

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Even with the rapidly expanding popularity of organocatalysts for organic reactions, chiral metal-based Lewis acid catalysts continue to have a uniquely important role in asymmetric reactions. Their broad applicability to cycloaddition and condensation reactions based on close encountered associations of Lewis base reactants with these chiral Lewis acid catalysts provides architecturally confined complexes that provide high stereocontrol in their chemical reactions.

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“…Changing the reducing condition led to a reversed configuration of 1,2-diol, producing 1,2-syn-diol 9b (Fig. 2), which is also a versatile synthon in natural product synthesis 30 .…”

Section: Table 2 Substrate Scopes Of Amine/ketone Dual Catalysis Amentioning

confidence: 99%

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

Cai¹,

Xu²,

Li³

et al. 2020

Preprint

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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 α-hydroxylation 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 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.

show abstract

Highly Enantioselective Carbonyl–Ene Reactions of 2,3‐Diketoesters: Efficient and Atom‐Economical Process to Functionalized Chiral α‐Hydroxy‐β‐Ketoesters

Cited by 16 publications

References 57 publications

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

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

The Future of Catalysis by Chiral Lewis Acids

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

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