Divergent α-functionalization of cyclic amines <i>via</i> ring construction by molecular O<sub>2</sub> oxidized dearomatization and ring deconstruction by aromatization-driven C–C σ-bond cleavage

Hu, Fangzhi; Wang, Liang; Ge, Chunyan; Li, Xinyao; Ding, Zhanshuai; Xu, Lubin; Li, Shuaishuai

doi:10.1039/d1gc00941a

Cited by 13 publications

(3 citation statements)

References 63 publications

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“…(2) The current application of the cascade [1,5]-hydride shift/cyclization strategy mainly focuses on the construction of five- and six-membered spiro-tetrahydroquinoline. However, exploration of building a spiro-architecture with a challenging ring size (like divergent synthesis of medium ring size) as well as conducting total synthesis of a structurally complex natural product remain elusive ( Li et al, 2018b ; Wang et al, 2018 ; Kataoka et al, 2019 ; Hu et al, 2020 ; Shen et al, 2020 ; Hu et al, 2021a ; Hu et al, 2021b ; Wang et al, 2021 ; Yang S. et al, 2021 ). (3) Notably, the application of [1,5]-hydride shift/cyclization strategy in stereoselective chemistry was barely reported ( Mori et al, 2018 ).…”

Section: Summary and Prospectmentioning

confidence: 99%

The Cascade [1,5]-Hydride Shift/Intramolecular C(sp3)–H Activation: A Powerful Approach to the Construction of Spiro-Tetrahydroquinoline Skeleton

Quan

Xie

et al. 2022

Front. Chem.

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The direct functionalization of inert C–H bonds is regarded as one of the most powerful strategies to form various chemical bonds and construct complex structures. Although significant advancements have been witnessed in the area of transition metal-catalyzed functionalization of inert C–H bonds, several challenges, such as the utilization and removal of expensive transition metal complexes, limited substrate scope and large-scale capacity, and poor atom economy in removing guiding groups coordinated to the transition metal, cannot fully fulfill the high standard of modern green chemistry nowadays. Over the past decades, due to its inherent advantage compared with a transition metal-catalyzed strategy, the hydride shift activation that applies “tert-amino effect” into the direct functionalization of the common and omnipresent C(sp3)–H bonds adjacent to tert-amines has attracted much attention from the chemists. In particular, the intramolecular [1,5]-hydride shift activation, as the most common hydride shift mode, enables the rapid and effective production of multifunctionally complex frameworks, especially the spiro-tetrahydroquinoline derivatives, which are widely found in biologically active natural products and pharmaceuticals. Although great accomplishments have been achieved in this promising field, rarely an updated review has systematically summarized these important progresses despite scattered reports documented in several reviews. Hence, in this review, we will summarize the significant advances in the cascade [1,5]-hydride shift/intramolecular C(sp3)-H functionalization from the perspective of “tert-amino effect” to build a spiro-tetrahydroquinoline skeleton, and the content is categorized by structure type of final spiro-tetrahydroquinoline products containing various pharmaceutical units. Besides, current limitations as well as future directions in this field are also pointed out. We hope our review could provide a quick look into and offer some inspiration for the research on hydride shift strategy in the future.

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Section: Summary and Prospectmentioning

confidence: 99%

The Cascade [1,5]-Hydride Shift/Intramolecular C(sp3)–H Activation: A Powerful Approach to the Construction of Spiro-Tetrahydroquinoline Skeleton

Quan

Xie

et al. 2022

Front. Chem.

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“…In this context, catalytic oxidative sp 3 C–H bond functionalization has gained increasing popularity over the decades for the synthesis of a variety of heterocyclic compounds . Particularly, in recent years, substituted amine-tethered α-sp 3 C–H bond functionalization emerged as a powerful tool for the synthesis of substituted N-heterocyclic scaffolds …”

Section: Introductionmentioning

confidence: 99%

DDQ/Fe(NO₃)₃-Catalyzed Aerobic Synthesis of 3-Acyl Indoles and an In Silico Study for the Binding Affinity of N-Tosyl-3-acyl Indoles toward RdRp against SARS-CoV-2

et al. 2023

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In the present study, we herein report a DDQ-catalyzed new protocol for the synthesis of substituted 3-acylindoles. Being a potential system for virtual hydrogen storage, introduction of catalytic DDQ in combination with Fe(NO3)3·9H2O and molecular oxygen as co-catalysts offers a regioselective oxo-functionalization of C-3 alkyl-/aryllidine indolines even with scale-up investigations. Intermediate isolation, their spectroscopic characterization, and the density functional theory calculations indicate that the method involves dehydrogenative allylic hydroxylation and 1,3-functional group isomerization/aromatization followed by terminal oxidation to afford 3-acylindoles quantitatively with very high regioselectivity. This method is very general for a large number of substrates with varieties of functional groups tolerance emerging high-yield outcome. Moreover, molecular docking studies were performed for some selected ligands with an RNA-dependent RNA polymerase complex (RdRp complex) of SARS-CoV-2 to illustrate the binding potential of those ligands. The docking results revealed that few of the ligands possess the potential to inhibit the RdRp of SARS-Cov-2 with binding energies (−6.7 to −8.19 kcal/mol), which are comparably higher with respect to the reported binding energies of the conventional re-purposed drugs such as Remdesivir, Ribavirin, and so forth (−4 to −7 kcal/mol).

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“…However, the activation of the C(sp 3 )–H bonds themselves is very difficult due to their high bond energies (typically 90–100 kcal/mol), low acidity (estimated p K a = 45–60), and unreactive molecular orbital profile . In fact, the synthesis of this type of compounds relies on the addition of prefabricated p -quinone methides ( p -QMs) to electrophiles (Scheme A). , Despite significant advances, the preparation of p -QM precursors requires harsh conditions. Moreover, for the synthesis of BHT derivatives, the use of strong acids or transition metal catalysts is generally inevitable, which leads to limited functional group tolerance and substrate types.…”

Section: Introductionmentioning

confidence: 99%

Selective Oxidative Methyl C–H Functionalization of Butylated Hydroxytoluene toward Arylimines/N-Heterocycles

Dong,

Wu,

Geng

et al. 2023

J. Org. Chem.

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A metal-free and selective oxidative methyl C–H functionalization of BHT with aniline compounds has been developed. This innovative method enables the facile and efficient synthesis of a diverse array of BHT-functionalized N-containing skeletons, including arylamines, benzoxazoles, benzothiazoles, benzimidazoles, quinazolines, and quinazolinones, all of which are challenging to access. The control experiment involving TEMP18O suggests that the radical adduct of TEMPO with the benzyl radical of BHT may serve as an intermediate.

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Divergent α-functionalization of cyclic amines via ring construction by molecular O₂ oxidized dearomatization and ring deconstruction by aromatization-driven C–C σ-bond cleavage

Abstract: An efficient approach to achieve the divergent α-C(sp3)–H functionalization of cyclic amines through an O2 oxidized dearomatization/ring construction and aromatization-driven ring deconstruction/intermolecular functionalization strategy was developed.

Cited by 13 publications

References 63 publications

The Cascade [1,5]-Hydride Shift/Intramolecular C(sp3)–H Activation: A Powerful Approach to the Construction of Spiro-Tetrahydroquinoline Skeleton

The Cascade [1,5]-Hydride Shift/Intramolecular C(sp3)–H Activation: A Powerful Approach to the Construction of Spiro-Tetrahydroquinoline Skeleton

DDQ/Fe(NO₃)₃-Catalyzed Aerobic Synthesis of 3-Acyl Indoles and an In Silico Study for the Binding Affinity of N-Tosyl-3-acyl Indoles toward RdRp against SARS-CoV-2

Selective Oxidative Methyl C–H Functionalization of Butylated Hydroxytoluene toward Arylimines/N-Heterocycles

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Divergent α-functionalization of cyclic amines via ring construction by molecular O2 oxidized dearomatization and ring deconstruction by aromatization-driven C–C σ-bond cleavage

Abstract: An efficient approach to achieve the divergent α-C(sp3)–H functionalization of cyclic amines through an O2 oxidized dearomatization/ring construction and aromatization-driven ring deconstruction/intermolecular functionalization strategy was developed.

Cited by 13 publications

References 63 publications

The Cascade [1,5]-Hydride Shift/Intramolecular C(sp3)–H Activation: A Powerful Approach to the Construction of Spiro-Tetrahydroquinoline Skeleton

The Cascade [1,5]-Hydride Shift/Intramolecular C(sp3)–H Activation: A Powerful Approach to the Construction of Spiro-Tetrahydroquinoline Skeleton

DDQ/Fe(NO3)3-Catalyzed Aerobic Synthesis of 3-Acyl Indoles and an In Silico Study for the Binding Affinity of N-Tosyl-3-acyl Indoles toward RdRp against SARS-CoV-2

Selective Oxidative Methyl C–H Functionalization of Butylated Hydroxytoluene toward Arylimines/N-Heterocycles

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Product

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Divergent α-functionalization of cyclic amines via ring construction by molecular O₂ oxidized dearomatization and ring deconstruction by aromatization-driven C–C σ-bond cleavage

DDQ/Fe(NO₃)₃-Catalyzed Aerobic Synthesis of 3-Acyl Indoles and an In Silico Study for the Binding Affinity of N-Tosyl-3-acyl Indoles toward RdRp against SARS-CoV-2