Cobalt‐Catalyzed α‐Arylation of Substituted α‐Bromo α‐Fluoro β‐Lactams with Diaryl Zinc Reagents: Generalization to Functionalized Bromo Derivatives

Lorion, Mélanie M.; Koch, Vanessa; Nieger, Martin; Chen, Hi-Yung; Lei, Aiwen; Bräse, Stefan; Cossy, Janine

doi:10.1002/chem.202001721

Cited by 22 publications

(4 citation statements)

References 32 publications

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“…For that reason we were also interested to prepare medicinally interesting 3-fluorinated trisubstituted β-lactams 7 . They were obtained from 5 in good yields and in nearly enantiopure form via the corresponding acid chloride and subsequent cyclization. , …”

Section: Resultsmentioning

confidence: 99%

Enantioenriched γ-Aminoalcohols, β-Amino Acids, β-Lactams, and Azetidines Featuring Tetrasubstituted Fluorinated Stereocenters via Palladacycle-Catalyzed Asymmetric Fluorination of Isoxazolinones

et al. 2021

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Enantiopure fluorine containing β-amino acids are of large biological and pharmaceutical interest. Strategies to prepare β-amino acid derivatives possessing a F-containing tetrasubstituted stereocenter at the α-C atom in a catalytic asymmetric sense are rare, in particular using an enantioselective electrophilic C–F bond formation. In the present study, a highly enantioselective palladacycle-catalyzed fluorination of isoxazolinones was developed. It is demonstrated that isoxazolinones are useful precursors toward enantiopure β-amino acid derivatives by diastereo- and chemoselective reduction. The formed γ-aminoalcohols served as valuable precursors toward β-amino acids, β-amino acid esters, and β-lactams, all featuring tetrasubstituted fluorinated stereocenters. In addition, by this work, enantioenriched fluorinated azetidines were accessible for the first time.

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Section: Resultsmentioning

confidence: 99%

Enantioenriched γ-Aminoalcohols, β-Amino Acids, β-Lactams, and Azetidines Featuring Tetrasubstituted Fluorinated Stereocenters via Palladacycle-Catalyzed Asymmetric Fluorination of Isoxazolinones

et al. 2021

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“…At the same time, −bromo −lactams have proven to be versatile synthons for the further functionalization of the −lactam core via cross-coupling reactions, [40][41][42][43][44] metal-halogen exchange followed by trapping with activated electrophiles [45][46][47] and also via nucleophilic bimolecular substitutions. [48][49][50] The known synthetic protocols for the preparation −bromo −lactams include thermal [2+2] cycloadditions of imines with bromoketenes or intramolecular SN2 cyclization of amides (Scheme 1C) [51][52][53][54][55][56][57][58][59][60][61][62][63][64] .…”

Section: Scheme 1 Methods For the Synthesis Of Monocyclic −Lactamsmentioning

confidence: 99%

Rapid and Highly Diastereoselective Synthesis of α-Bromo N-Alkoxy β-Lactams from α,β-Unsaturated Silyl Imino Ethers

Rodriguez Trevino,

Pandiri,

Loch-Temzelides

et al. 2023

Preprint

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The preparation of the β-lactam motif containing both C-Br and N-O bonds as functional handles remains an unmet synthetic challenge. Described herein is a novel diastereoselective NBS-mediated cyclization of N-alkoxy α,β-unsaturated silyl imino ethers to furnish nearly three dozen α-bromo N-alkoxy β-lactams. The reaction gives rapid and convenient access to structurally diverse monocyclic, spirocyclic and fused β-lactams in moderate to good yields. The two functional handles were shown to be useful for the further elaboration of the β-lactam core.

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“…[30] Thef irst monofluoroalkylation catalyzed by cobalt was reported by Cossy in 2020. [31] a-Fluoro-a-bromolactams underwent diastereoselective cross couplings with diarylzinc and diallylzinc reagents in high yields and excellent diastereoselectivities in the presence of cobalt(II) chloride and tetramethyl ethylene diamine (Scheme 14).…”

Section: Palladium-catalyzed Cross Couplings Of A-fluoro Alkyl Halidesmentioning

confidence: 99%

Transition‐Metal‐Catalyzed Monofluoroalkylation: Strategies for the Synthesis of Alkyl Fluorides by C−C Bond Formation

2021

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Alkyl fluorides modulate the conformation, lipophilicity, metabolic stability, and pKa of compounds containing aliphatic motifs and, therefore, have been valuable for medicinal chemistry. Despite significant research in organofluorine chemistry, the synthesis of alkyl fluorides, especially chiral alkyl fluorides, remains a challenge. Most commonly, alkyl fluorides are prepared by the formation of C−F bonds (fluorination), and numerous strategies for nucleophilic, electrophilic, and radical fluorination have been reported in recent years. Although strategies to access alkyl fluorides by C−C bond formation (monofluoroalkylation) are inherently convergent and complexity‐generating, they have been studied less than methods based on fluorination. This Review provides an overview of recent developments in the synthesis of chiral (enantioenriched or racemic) secondary and tertiary alkyl fluorides by monofluoroalkylation catalyzed by transition‐metal complexes. We expect this contribution will illuminate the potential of monofluoroalkylations to simplify the synthesis of complex alkyl fluorides and suggest further research directions in this growing field.

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Cobalt‐Catalyzed α‐Arylation of Substituted α‐Bromo α‐Fluoro β‐Lactams with Diaryl Zinc Reagents: Generalization to Functionalized Bromo Derivatives

Cited by 22 publications

References 32 publications

Enantioenriched γ-Aminoalcohols, β-Amino Acids, β-Lactams, and Azetidines Featuring Tetrasubstituted Fluorinated Stereocenters via Palladacycle-Catalyzed Asymmetric Fluorination of Isoxazolinones

Enantioenriched γ-Aminoalcohols, β-Amino Acids, β-Lactams, and Azetidines Featuring Tetrasubstituted Fluorinated Stereocenters via Palladacycle-Catalyzed Asymmetric Fluorination of Isoxazolinones

Rapid and Highly Diastereoselective Synthesis of α-Bromo N-Alkoxy β-Lactams from α,β-Unsaturated Silyl Imino Ethers

Transition‐Metal‐Catalyzed Monofluoroalkylation: Strategies for the Synthesis of Alkyl Fluorides by C−C Bond Formation

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