Strategic Approach to the Metamorphosis of γ-Lactones to NH γ-Lactams via Reductive Cleavage and C–H Amidation

Jung, Ho Yun; Chang, Sukbok; Hong, Sungwoo

doi:10.1021/acs.orglett.9b02673

Cited by 18 publications

(17 citation statements)

References 46 publications

(15 reference statements)

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“…C NMR (101 MHz, CDCl3) δ 146.6, 146.5, 146.0, 143.2, 137.3, 134.2, 126.4, 125.7, 125.5, 121.4, 119.8, 119.7, 114.5, 110.6, 106.1, 105.6, 31.4, 31.4. The data match with literature 22. …”

supporting

confidence: 87%

See 1 more Smart Citation

Carbon Chain Rupture: Base-Induced Radical C–C Bond Cleavage of Alkylbenzimidazoles

Guo

Yan

et al. 2022

Synthesis

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A base mediated aerobic oxidation of alkyl benzimidazoles for the preparation of carboxylic acid. A number of aliphatic carboxylic acids have been prepared in good to excellent yields via C–C bond rupture processes. Preliminary mechanistic studies suggested the reaction underwent a radical pathway initiated by strong bases such as potassium amide. This type of transformation provides an alternative strategy for the access of important carboxylic acid moieties.

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“…C NMR (101 MHz, CDCl3) δ 146.6, 146.5, 146.0, 143.2, 137.3, 134.2, 126.4, 125.7, 125.5, 121.4, 119.8, 119.7, 114.5, 110.6, 106.1, 105.6, 31.4, 31.4. The data match with literature 22. …”

supporting

confidence: 87%

“…The data match with literature. 22 2-(1-Methyl-1H-benzo[d]imidazol-2-yl)propan-2-ol (3c). Protocol A was followed, 1-Methyl-2-undecyl-1H-benzo[d]imidazole (1m) (34.8 mg, 0.2 mmol) was employed as the substrate.…”

Section: -Bromomentioning

confidence: 99%

Carbon Chain Rupture: Base-Induced Radical C–C Bond Cleavage of Alkylbenzimidazoles

Guo

Yan

et al. 2022

Synthesis

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“…We also developed a synthetic approach to convert lactones to the corresponding NH-lactams with interesting biological activities. 35 We next turned our attention to aryl C(sp 2 )−H bond amidation by utilizing the Cp*Ir(κ 2 -LX) catalyst system. In fact, Driver 36 and Falck 37 reported that processes using aryl azides and hydroxylamines with dirhodium(II) catalysts proceed via electrocyclization and electrophilic aromatic substitution (S E Ar), respectively.…”

Section: Co and Ru Catalysismentioning

confidence: 99%

“…This amidation protocol was highly effective even with more complex substrates that possess multiple competing C–H bonds, and it was well-suited for derivatizing naturally occurring carboxylic acids at the late synthetic stage. We also developed a synthetic approach to convert lactones to the corresponding NH -lactams with interesting biological activities …”

Section: C–n Bond Formation: Outer-sphere Pathwaymentioning

confidence: 99%

Mechanism-Guided Development of Transition-Metal-Catalyzed C–N Bond-Forming Reactions Using Dioxazolones as the Versatile Amidating Source

et al. 2021

Self Cite

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Conspectus Catalytic reactions that construct carbon–nitrogen bonds are one of central themes in both synthetic and medicinal chemistry since the obtainable nitrogen-containing motifs are commonly encountered in natural products and have also seen a growing prominence as key structural features in marketed drugs and preclinical candidates. Pd-catalyzed cross-couplings, such as Buchwald–Hartwig amination, are at the forefront of such synthetic methods in practical settings. However, they require prefunctionalized substrates such as (hetero)aryl halides that must be prepared independently, often by multiple operations. One emerging way to circumvent these preparatory steps and directly convert ubiquitous C–H bonds into valuable C–N bonds is catalytic C–H amination, which allows synthetic chemists to devise shorter and more efficient retrosynthetic schemes. The past two decades have witnessed considerable progress in expanding the repertoire of this strategy, especially by identifying effective amino group precursors. In this context, dioxazolones have experienced a dramatic resurgence in recent years as a versatile nitrogen source in combination with transition-metal catalyst systems that facilitate decarboxylation to access key metal-acylnitrenoid intermediates. In addition to their high robustness and easy accessibility from abundant carboxylic acids, the unique reactivity of the transient intermediates in the amido group transfer has led to a fruitful journey for mild and efficient C–H amidation reactions. This Account summarizes our recent contributions to the development of C–N bond-forming reactions using dioxazolones as effective nitrenoid precursors, which are categorized into two subsets according to their mechanistic differences: inner- versus outer-sphere pathways. The first section describes how we could unveil the synthetic potential of dioxazolones in the realm of the inner-sphere C–H amidation, where we demonstrated that dioxazolones serve not only as manageable alternatives to acyl azides but also as highly efficient reagents to significantly reduce the catalyst loading and temperature. Taking advantage of the mild conditions in combination with group 9 Cp*M complexes (M = Rh, Ir, Co) or isoelectronic Ru species, we have dramatically expanded the accessible synthetic scope. Mechanistic investigations revealed that the putative metal-nitrenoid species is involved as a key intermediate during catalysis, which leads to facile C–N bond formation. On the basis of the mechanistic underpinning, we have succeeded in developing novel catalytic platforms that harness the intermediacy of metal-nitrenoids to explore C–H insertion chemistry via an outer-sphere pathway. Indeed, the tailored catalysts were capable of suppressing the competitive Curtius-type decomposition, thus granting access to versatile lactam products. We have further repurposed the catalytic systems upon modification of chelating ligands and also the identity of the transition metal to achieve three goals: (i) addressing selectivity issues to...

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“…The carboxyl group of 2 a could be easily transformed to acyl chloride and further to ester and amide, providing 6 a in 76 % yield with 94 % ee and 7 a in 66 % yield with 94 % ee . In particular, ring opening of the chiral lactone 6 a could be achieved by subsequent hydrogenation of carbon‐carbon double bond and reductive cleavage of C−O bond with Pd/C, [37] giving monoester 8 a in 60 % yield with 92 % ee . In the previous report, monoester 8 a was synthesized by PLE‐catalyzed kinetic resolution from the prochiral diester for up to 7 days with only 36 % ee [38] .…”

Section: Resultsmentioning

confidence: 99%

Gold‐Catalyzed Desymmetric Lactonization of Alkynylmalonic Acids Enabled by Chiral Bifunctional P,N ligands

et al. 2022

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Due to the linear coordination nature of gold(I) catalysts, achieving high enantiocontrol in asymmetric gold catalysis is a great challenge. To improve the enantiocontrol of gold catalysis, an ion-pairing strategy was therefore proposed. A series of bifunctional P,N ligands based on chiral spirocyclic and biaryl scaffolds were synthesized and applied in the gold(I)-catalyzed desymmetric lactonization of alkynylmalonic acids. A wide range of chiral lactones containing an α-position quaternary stereocenter were synthesized with high yields, excellent regioselectivity and enantioselectivity under mild reaction conditions. The synthetic utilities of the current reaction were demonstrated by gram-scale synthesis and transformations of chiral lactones. The origin of enantioselectivity and the role of the alcohol additive were elucidated via control experiments and DFT calculations.

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Strategic Approach to the Metamorphosis of γ-Lactones to NH γ-Lactams via Reductive Cleavage and C–H Amidation

Cited by 18 publications

References 46 publications

Carbon Chain Rupture: Base-Induced Radical C–C Bond Cleavage of Alkylbenzimidazoles

Carbon Chain Rupture: Base-Induced Radical C–C Bond Cleavage of Alkylbenzimidazoles

Mechanism-Guided Development of Transition-Metal-Catalyzed C–N Bond-Forming Reactions Using Dioxazolones as the Versatile Amidating Source

Gold‐Catalyzed Desymmetric Lactonization of Alkynylmalonic Acids Enabled by Chiral Bifunctional P,N ligands

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