Regioselective Hydroaminoalkylation with Silylated Alkenes for β-Amino Acid Synthesis DOI

M. THOMPSON,

Decheng Yang, J. S. Higgins

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Catalyst and substrate steric electronic features that influence regioselectivity in hydroaminoalkylation were leveraged to develop a synthetic approach for the selective synthesis of β-amino acids. An situ generated tantalum-ureate catalyst was used prepare 18 γ-silylated amines up 93% yield from internal silylated alkenes. β-Amino silane regioisomer production rarely observed, making this work one few examples highly regioselective with unsymmetric These γ-amino silanes converted alcohols modified Tamao-Fleming oxidation strategy followed by two additional steps acids, including key fragment anticancer drug candidate Ipatasertib.

Language: Английский

Native Amides as Enabling Vehicles for Forging sp3–sp3 Architectures via Interrupted Deaminative Ni-Catalyzed Chain-Walking DOI Creative Commons
Jesus Rodrigalvarez, Hao Wang, Rubén Martı́n

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 3869 - 3874

Published: Feb. 8, 2023

Herein, we disclose an interrupted deaminative Ni-catalyzed chain-walking strategy that forges sp3-sp3 architectures at remote, yet previously unfunctionalized, methylene sp3 C-H sites enabled by the presence of native amides. This protocol is characterized its mild conditions and wide scope, including challenging substrate combinations. Site-selectivity can be dictated a judicious choice ligand, thus offering opportunity to enable bond formations are otherwise inaccessible in conventional events.

Language: Английский

Citations

57
Kinetically-Controlled Ni-Catalyzed Direct Carboxylation of Unactivated Secondary Alkyl Bromides without Chain Walking DOI Creative Commons
Jacob Davies, Julien R. Lyonnet,

Bjørn Carvalho

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(3), P. 1753 - 1759

Published: Jan. 9, 2024

Herein, we report the direct carboxylation of unactivated secondary alkyl bromides enabled by merger photoredox and nickel catalysis, a previously inaccessible endeavor in arena. Site-selectivity is dictated kinetically controlled insertion CO2 at initial C(sp3)–Br site rapid formation Ni(I)–alkyl species, thus avoiding undesired β-hydride elimination chain-walking processes. Preliminary mechanistic experiments reveal subtleties stereoelectronic effects for guiding reactivity site-selectivity.

Language: Английский

Citations

16
Nickel/Photoredox Dual-Catalyzed Regiodivergent Aminoalkylation of Unactivated Alkyl Halides DOI
Wenlong Wang, Xueyuan Yan, Ye Fu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(42), P. 23385 - 23394

Published: Oct. 12, 2023

A mild and regiodivergent aminoalkylation of unactivated alkyl halides is disclosed via a dual photoredox/nickel catalysis. Bipyridyl-type ligands without an ortho-substituent control the site-selective coupling at original position, while ortho-disubstituted tune site-selectivity remote, unprefunctionalized position. Mechanistic studies combined with DFT calculations give insight into mechanism origins ligand-controlled regioselectivity. Notably, this redox-neutral, alkyl-alkyl features conditions, broad substrate scope for both partners, excellent offers straightforward way α-alkylation tertiary amines to synthesize structurally diverse alkylamines value-added amino acid derivatives.

Language: Английский

Citations

29
Electrochemical NiH‐Catalyzed C(sp3)−C(sp3) Coupling of Alkyl Halides and Alkyl Alkenes DOI Open Access
Pengfei Li,

Guangsheng Kou,

Tian Feng

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(44)

Published: Sept. 14, 2023

Herein, an electrochemically driven NiH-catalyzed reductive coupling of alkyl halides and alkenes for the construction Csp3 -Csp3 bonds is firstly reported. Notably, serve dual function as substrates hydrogen sources to generate NiH species under electrochemical conditions. The tunable nature this reaction realized by introducing intramolecular coordinating group substrate, where product can be easily adjusted give desired branched products. method proceeds mild conditions, exhibits a broad substrate scope, affords moderate excellent yields with over 70 examples, including late-stage modification natural products drug derivatives. Mechanistic insights offer evidence process. sp3 -carbon-halogen activated through single electron transfer (SET) nickel catalyst in its low valence state, generated cathodic reduction, generation from pivotal transformation.

Language: Английский

Citations

24
Photocatalytic carboxylation of styrenes with CO2 via C=C double bond cleavage DOI

Ke-Gong Cao,

Tianyu Gao, Li‐Li Liao

et al.

CHINESE JOURNAL OF CATALYSIS (CHINESE VERSION), Journal Year: 2024, Volume and Issue: 56, P. 74 - 80

Published: Jan. 1, 2024

Language: Английский

Citations

12
Strategies and Mechanisms of First-Row Transition Metal-Regulated Radical C–H Functionalization DOI
Xinghua Wang,

J. P. He,

Yanan Wang

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(17), P. 10192 - 10280

Published: Aug. 8, 2024

Radical C–H functionalization represents a useful means of streamlining synthetic routes by avoiding substrate preactivation and allowing access to target molecules in fewer steps. The first-row transition metals (Ti, V, Cr, Mn, Fe, Co, Ni, Cu) are Earth-abundant can be employed regulate radical functionalization. use such is desirable because the diverse interaction modes between metal complexes species including addition center, ligand complexes, substitution single-electron transfer radicals hydrogen atom noncovalent complexes. Such interactions could improve reactivity, diversity, selectivity transformations allow for more challenging reactions. This review examines achievements this promising area over past decade, with focus on state-of-the-art while also discussing existing limitations enormous potential high-value regulated these metals. aim provide reader detailed account strategies mechanisms associated

Language: Английский

Citations

12
Ligand-Controlled Regioreversed 1,2-Aryl-Aminoalkylation of Alkenes Enabled by Photoredox/Nickel Catalysis DOI
Ye Fu,

Songlin Zheng,

Yixin Luo

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(11), P. 8505 - 8517

Published: May 16, 2024

A ligand-controlled regioreversed 1,2-arylalkylation of alkenes via photoredox/nickel dual catalysis is reported. In contrast with previous reports on photoredox/nickel-catalyzed 1,2-alkylarylation reactions that initiate from the Giese addition an alkyl radical to alkene, this three-component conjugate coupling process occurs through nickel-catalyzed aryl thereby leading a complementary regioselectivity conventional 1,2-alkylarylation. An ortho-substituted bipyridyl ligand key tune regioselectivity, which was found be dictated by reactivity alkene-coordinated LnNi(0) complexes trigger formation radicals halogen-atom transfer (XAT). This transformation allows concise entry structurally abundant β-amino acid derivatives, including ORL1-receptor antagonists.

Language: Английский

Citations

10
Ligand-Controlled Regiodivergent Nickel-Catalyzed Hydroaminoalkylation of Unactivated Alkenes DOI
Tianze Zhang, Shan Jiang,

Mengying Qian

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 3458 - 3470

Published: Jan. 25, 2024

Ligand modulation of transition-metal catalysts to achieve optimal reactivity and selectivity in alkene hydrofunctionalization is a fundamental challenge synthetic organic chemistry. Hydroaminoalkylation, an atom-economical approach for alkylating amines using alkenes, particularly significant amine synthesis the pharmaceutical, agrochemical, fine chemical industries. However, existing methods usually require specific substrate combinations precise regio- stereoselectivity, which limits their practical utility. Protocols allowing regiodivergent hydroaminoalkylation from same starting materials, controlling both regiochemical stereochemical outcomes, are currently absent. Herein, we report ligand-controlled, nickel-catalyzed unactivated alkenes with

Language: Английский

Citations

9
Accessing Fluorinated Tertiary Homoallylamines via Photocatalytic Defluorinative Aminoalkylation of Fluoroalkyl-Substituted Alkenes DOI

Wenhui Xiong,

Guangyu Sun, Meijuan Zhou

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(11), P. 8252 - 8260

Published: May 13, 2024

Due to their appealing physiological attributes, tertiary aliphatic amines are pervasive in a myriad of biologically active molecules. In particular, featuring homoallylic substituents serve as versatile synthetic building blocks. Therefore, there is growing demand for the development practical and modular methods rapid assembly sp3-rich complex from readily accessible chemical feedstock. Here, we disclose multicomponent, reductive photocatalytic protocol that merges secondary alkylamines, carbonyl compounds, fluoroalkyl-substituted alkenes, yielding fluorinated homoallylamines. This defluorinative aminoalkylation involves addition alkyl-substituted α-amino radicals, generated reduction situ-generated iminium ions by photocatalyst, alkenes subsequent fluoride elimination, reliably furnishing gem-difluoroalkene monofluoroalkene motifs not easily through alternative methods. Utility method was demonstrated its broad functional group compatibility, derivatization synthesis drug analogues.

Language: Английский

Citations

8
Enantioselective Ni-Catalyzed 1,2-Borylalkynylation of Unactivated Alkenes DOI
Jie Huang, Xueyuan Yan,

Xuan‐Yu Liu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(25), P. 17140 - 17149

Published: June 12, 2024

Enantioselective three-component difunctionalization of alkenes with boron reagents represents an attractive strategy for assembling three-dimensional chiral organoboron compounds. However, regio- and enantiocontrol comprise the pivot challenges in these transformations, which predominantly require use activated conjugated alkenes. Herein, by utilizing various carbonyl directing groups, including amides, sulfinamides, ketones, esters, we succeed realizing a nickel-catalyzed 1,2-borylalkynylation unactivated to enable simultaneous incorporation entity sp-fragment across double bond. The products contain boryl, alkynyl, functional groups orthogonal synthetic reactivities, offering three handles further derivatization access valuable intermediates. utility this ligand-enabled asymmetric protocol has been highlighted through late-stage decoration drug-relevant molecules.

Language: Английский

Citations

8