Peptide Late-Stage Diversifications by Rhodium-Catalyzed Tryptophan C7 Amidation

Wang, Wei; Wu, Jun; Kuniyil, Rositha; Kopp, Adelina; Lima, Rafaely N.; Ackermann, Lutz

doi:10.1016/j.chempr.2020.10.026

Cited by 68 publications

(40 citation statements)

References 76 publications

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“…65 This C−H amination protocol reinvented latestage peptide diversifications to obtain C7-decorated tryptophan peptides. 66 The chelation-assisted approach was elegantly applied to a three-component transformation for the convergent synthesis of α-branched amines (Scheme 34). 67 A wide range of substrates bearing oxime-, amide-, and pyrazole-based directing groups were readily reacted with terminal alkenes and dioxazolones via a 1,1-addition pathway involving β-hydride elimination and hydride reinsertion.…”

Section: Additional Synthetic Utilities Ofmentioning

confidence: 99%

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

et al. 2021

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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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Section: Additional Synthetic Utilities Ofmentioning

confidence: 99%

“…Such a desymmetrization approach also enabled the construction of chiral sulfur stereogenic centers by the He group . This C–H amination protocol reinvented late-stage peptide diversifications to obtain C7-decorated tryptophan peptides …”

Section: Additional Synthetic Utilities Of Dioxazolonesmentioning

confidence: 99%

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

et al. 2021

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“…The late-stage modification of peptides has received increasing attention due to the convenient and efficient modality. However, such protocols generally require substrate prefunctionalization and expensive metal catalysts, such as Pd [ 66 – 87 ], Rh [ 88 – 91 ], and Ru [ 92 – 93 ]. In 2019, the Ackermann group demonstrated that a manganese(I) catalyst enabled the late-stage C–H allylation of structurally complex peptides in a site-selective fashion ( Scheme 10 ) [ 94 ].…”

Section: Reviewmentioning

confidence: 99%

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

Son¹

2021

Beilstein J. Org. Chem.

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The late-stage C–H functionalization of bioactive structural motifs is a powerful synthetic strategy for accessing advanced agrochemicals, bioimaging materials, and drug candidates, among other complex molecules. While traditional late-stage diversification relies on the use of precious transition metals, the utilization of 3d transition metals is an emerging approach in organic synthesis. Among the 3d metals, manganese catalysts have gained increasing attention for late-stage diversification due to the sustainability, cost-effectiveness, ease of operation, and reduced toxicity. Herein, we summarize recent manganese-catalyzed late-stage C–H functionalization reactions of biologically active small molecules and complex peptides.

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“…In C(sp 2 )-H directed functionalizations, C-H amidations constitute interesting alternatives to Buchwald-Hartwig, Ullmann or Chan-Lam strategies particularly within the context of medicinal chemistry in which amide bonds associated with N-heterocyclic platforms are prevalent in drug candidates [13,14]. As a matter of illustration, Scheme 3 highlights a non-exhaustive collection of C-H amidation products described in the last two years [15][16][17][18][19][20][21][22][23][24]. In C(sp 2 )-H directed functionalizations, C-H amidations constitute interesting alternatives to Buchwald-Hartwig, Ullmann or Chan-Lam strategies particularly within the context of medicinal chemistry in which amide bonds associated with N-heterocyclic platforms are prevalent in drug candidates [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…In C(sp 2 )-H directed functionalizations, C-H amidations constitute interesting alternatives to Buchwald-Hartwig, Ullmann or Chan-Lam strategies particularly within the context of medicinal chemistry in which amide bonds associated with N-heterocyclic platforms are prevalent in drug candidates [13,14]. As a matter of illustration, Scheme 3 highlights a non-exhaustive collection of C-H amidation products described in the last two years [15][16][17][18][19][20][21][22][23][24]. The potential of C(sp 2 )-H functionalizations has been brilliantly illustrated by Ellman and Miller in the structural diversification of thiostrepton, a potent antibiotic peptide leading to analogs with maintained biological activities while increasing aqueous solubility (up to 28-fold) (Scheme 4) [25].…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Catalytic C-H Amidations: An Highlight

2021

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The crucial role played by compounds bearing amide functions, not only in biological processes but also in several fields of chemistry, life polymers and material sciences, has brought about many significant discoveries and innovative approaches for their chemical synthesis. Indeed, a plethora of strategies has been developed to reach such moieties. Amides within chiral molecules are often associated with biological activity especially in life sciences and medicinal chemistry. In most of these cases, their synthesis requires extensive rethinking methodologies. In the very last years (2019–2020), enantioselective C-H functionalization has appeared as a straightforward alternative to reach chiral amides. Therein, an overview on these transformations within this timeframe is going to be given.

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Peptide Late-Stage Diversifications by Rhodium-Catalyzed Tryptophan C7 Amidation

Cited by 68 publications

References 76 publications

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

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

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

Enantioselective Catalytic C-H Amidations: An Highlight

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