Regioselective hydroamination of unactivated olefins with diazirines as a diversifiable nitrogen source DOI Creative Commons

Qingyu Xing,

Preeti P. Chandrachud,

Khalilia Tillett

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 18, 2024

Abstract Nitrogen-containing compounds, such as amines, hydrazines, and heterocycles, play an indispensable role in medicine, agriculture, materials. Alkylated derivatives of these especially sterically congested environments, remain a challenge to prepare. Here we report versatile method for the regioselective hydroamination readily available unactivated olefins with diazirines. Over fifty examples are reported, including protecting group-free amination fourteen different natural products. A broad functional group tolerance includes alcohols, ketones, aldehydes, epoxides. The proximate products reactions diaziridines, which, under mild conditions, converted primary heterocycles. Five target- diversity-oriented syntheses pharmaceutical compounds shown, along preparation bis- 15 N diazirine validated late-stage isotopic labeling RNA splicing modulator candidate. In this work, using ( 1 ) electrophilic nitrogen source reaction, diversification resulting diaziridines.

Language: Английский

Anti-Markovnikov Intermolecular Hydroamination of Alkenes and Alkynes: A Mechanistic View DOI Creative Commons
Jorge Escorihuela, Agustı́ Lledós, Gregori Ujaque

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(15), P. 9139 - 9203

Published: July 5, 2023

Hydroamination, the addition of an N–H bond across a C–C multiple bond, is reaction with great synthetic potential. Important advances have been made in last decades concerning catalysis these reactions. However, controlling regioselectivity amine toward formation anti-Markovnikov products (addition to less substituted carbon) still remains challenge, particularly intermolecular hydroaminations alkenes and alkynes. The goal this review collect systems which hydroamination terminal alkynes has achieved. focus will be placed on mechanistic aspects such reactions, discern step at decided unravel factors that favor regioselectivity. In processes entailing direct alternative pathways, involving several reactions accomplish (formal processes), also discussed review. catalysts gathered embrace most metal groups Periodic Table. Finally, section discussing radical-mediated metal-free approaches, as well heterogeneous catalyzed processes, included.

Language: Английский

Citations

57
Recent advances in C(sp3)–N bond formation via metallaphoto-redox catalysis DOI
Juan Zhang,

Xiao-Die Huan,

Xin Wang

et al.

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(50), P. 6340 - 6361

Published: Jan. 1, 2024

In this review, the state-of-the-art advances in radical-involved C(sp 3 )–N bond formation via metallaphotoredox catalysis have been highlighted, which are organized according to different catalytic modes, reaction types, and substrate classes.

Language: Английский

Citations

11
Photoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis DOI
Wesley Harrison, Guangde Jiang, Zhengyi Zhang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(15), P. 10716 - 10722

Published: April 5, 2024

Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored with dialkyl amine-derived nitrogen-centered radicals since designing a catalytic system generate aminium cation, suppress deleterious side reactions such as α-deprotonation H atom abstraction, facilitate enantioselective hydrogen transfer formidable task. Herein, we describe application of photoenzymatic catalysis harness cation for intermolecular hydroamination. In reaction, flavin-dependent ene-reductase photocatalytically generates from corresponding hydroxylamine catalyzes hydroamination furnish enantioenriched tertiary amine, whereby enantioinduction occurs through enzyme-mediated transfer. This work highlights use control highly reactive intermediates synthesis, addressing long-standing challenge chemical synthesis.

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
Photocatalytic Anti-Markovnikov Hydroamination of Alkenes with Primary Heteroaryl Amines DOI
Eric P. Geunes, Jonathan M. Meinhardt, Emily J. Wu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(40), P. 21738 - 21744

Published: Oct. 3, 2023

We report a light-driven method for the intermolecular anti-Markovnikov hydroamination of alkenes with primary heteroaryl amines. In this protocol, electron transfer between an amine substrate and excited-state iridium photocatalyst affords aminium radical cation (ARC) intermediate that undergoes C–N bond formation nucleophilic alkene. Integral to reaction success is electronic character amine, wherein increasingly electron-deficient amines generate reactive ARCs. Counteranion-dependent reactivity observed, triflate photocatalysts are employed in place conventional hexafluorophosphate complexes. This exhibits broad functional group tolerance across 55 examples N-alkylated products derived from pharmaceutically relevant

Language: Английский

Citations

21
Escape from Hydrofunctionalization: Palladium Hydride‐Enabled Difunctionalization of Conjugated Dienes and Enynes DOI Creative Commons
Ziyan Zhang, Vladimir Gevorgyan

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(47)

Published: Oct. 3, 2023

Abstract Palladium hydrides are traditionally employed in hydrofunctionalization (i.e. monofunctionalization) of conjugated dienes and enynes, owning to its facile protic hydropalladation electron‐rich (or neutral) unsaturated bonds. Herein, we report a mild PdH‐catalyzed difunctionalization enynes. This protocol is enabled by the chemoselectivity switch initial step achieved visible light enhancement hydricity PdH species. method allows for cascade annulation enynes with various easily available abundant substrates, such as acrylic acids, amides, Baylis–Hillman adducts, toward wide range alkenyl or alkynyl lactones, lactams, tetrahydrofurans. also provides an easy access complex spiro‐fused tricyclic frameworks.

Language: Английский

Citations

18
Silanes as a versatile hydride source for Ni–H catalysis: a promising tool for π-hydro functionalization DOI
Yafia Kousin Mirza, Partha Sarathi Bera, Sachin Balaso Mohite

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(15), P. 4290 - 4317

Published: Jan. 1, 2024

Nickel-catalyzed hydrofunctionalization of π-substrates is a possibly effective method to synthesize several value-added molecular architectures. This review covers the NiH catalyzed reactions alkenes, alkynes and allenes.

Language: Английский

Citations

6
Direct C(sp3)-H functionalization with aryl and alkyl radicals as intermolecular hydrogen atom transfer (HAT) agents DOI
Jia‐Lin Tu, Binbin Huang

Chemical Communications, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Recent years have witnessed the emergence of direct intermolecular C(sp

Language: Английский

Citations

6
NiH-catalyzed C–N bond formation: insights and advancements in hydroamination of unsaturated hydrocarbons DOI Creative Commons
Changseok Lee, Hyung‐Joon Kang, Sungwoo Hong

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 15(2), P. 442 - 457

Published: Dec. 6, 2023

The formation of C-N bonds is a fundamental aspect organic synthesis, and hydroamination has emerged as pivotal strategy for the synthesis essential amine derivatives. In recent years, there been surge interest in metal hydride-catalyzed reactions common alkenes alkynes. This method avoids need stoichiometric organometallic reagents overcomes problems associated with specific compounds that may impact functional group compatibility. Notably, developments have brought to forefront olefinic hydroamidation facilitated by nickel hydride (NiH) catalysis. inclusion suitable chiral ligands paved way realization asymmetric realm olefins. review aims provide an in-depth exploration latest achievements bond through intermolecular catalyzed hydrides. Leveraging this innovative approach, diverse range alkene alkyne substrates can be efficiently transformed into value-added enriched bonds. intricacies are succinctly elucidated, offering concise overview underlying reaction mechanisms. It our aspiration comprehensive will stimulate further progress NiH-catalytic techniques, fine-tune systems, drive innovation catalyst design, foster deeper understanding

Language: Английский

Citations

14
The Effect of Basic Ligands and Alkenes on the Regioselectivity of C−H Additions of Tertiary Amines to Alkenes DOI
Da Li, Yuji Wang, Shiyu Wang

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(32)

Published: April 4, 2024

Abstract Highly regioselective C−H alkylation reactions of tertiary anilines and alkyl amines with simple alkenes have been achieved by the use imidazolin‐2‐iminato scandium complexes. This protocol provided an efficient atom‐economical route to structurally diverse amine derivatives. The basic ligand, a coordinating THF in catalyst substitution alkene substrates were found switch regioselectivity presumably due generation different types catalytically active species or formation relatively stable intermediates. On basis deuterium labeling experiments KIE experiments, possible catalytical cycles understand reaction mechanism as well regioselectivity.

Language: Английский

Citations

5