Modular Synthesis of Heterobenzylic Amines via Carbonyl Azinylative Amination DOI Creative Commons
Alex A. Rafaniello, Roopender Kumar,

Rachel C. Phillips

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(42)

Published: July 12, 2024

Abstract Transformations enabling the synthesis of α‐alkyl, α′‐2‐azinyl amines by addition 2‐heteroaryl‐based nucleophiles to in situ ‐ generated and non‐activated alkyl‐substituted iminium ions are extremely rare. Approaches involving classical 2‐azinyl organometallics, such as corresponding Grignard reagents, often fail produce desired products. Here, we report an operationally straightforward solution this problem through development a multicomponent coupling process wherein soft indium nucleophile, from 2‐iodo heteroarene powder, adds ion that is also formed directly reaction. This modular carbonyl azinylative amination (CAzA) displays broad scope only metal reductant needed generate reactive nucleophile. Beyond ions, polyfluoromethyl ketones forms tertiary alcohols. Together, products these reactions possess high degree functionality, typically challenging synthesize other methods, contain motifs recognized privileged context pharmaceuticals agrochemicals.

Language: Английский

General (hetero)polyaryl amine synthesis via multicomponent cycloaromatization of amines DOI Creative Commons
Lebin Su, Jianyu Dong, Yangyang Shen

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Language: Английский

Citations

3
A General Three-Component Alkyl Petasis Boron–Mannich Reaction DOI
Chao Hu, Jet Tsien,

Si-Jie Chen

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(31), P. 21769 - 21777

Published: July 29, 2024

Aryl amines are one of the most common moieties in biologically active molecules, and approximately 37% drug candidates contain aromatic amines. Recent advancements medicinal chemistry, coined "escaping from flatland", have led to a greater focus on accessing highly functionalized C (sp3)-rich improve physicochemical pharmacokinetic properties compounds. This article presents modular operationally straightforward three-component alkyl Petasis boron–Mannich (APBM) reaction that utilizes ubiquitous starting materials, including amines, aldehydes, boronates. By adaptation this transformation high-throughput experimentation (HTE), it offers rapid access an array diverse C(sp3)-rich complex amenable for identification candidates.

Language: Английский

Citations

9
Acridine photocatalysis enables tricomponent direct decarboxylative amine construction DOI Creative Commons
Xianwei Sui, Hang T. Dang,

Arka Porey

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(25), P. 9582 - 9590

Published: Jan. 1, 2024

Diverse amines and amino acids are now readily accessed from carboxylic acids, aldehydes, amine precursors in a direct decarboxylative reaction enabled by homogeneous triple catalytic system based on acridine photocatalysis.

Language: Английский

Citations

9
Titanium in photocatalytic organic transformations: current applications and future developments DOI
Jia‐Lin Tu, Binbin Huang

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(33), P. 6650 - 6664

Published: Jan. 1, 2024

Titanium, as an important transition metal, has garnered extensive attention in both industry and academia due to its excellent mechanical properties, corrosion resistance, unique reactivity organic synthesis. In the field of photocatalysis, titanium-based compounds such titanium dioxide (TiO

Language: Английский

Citations

6
Multicomponent Construction of Tertiary Alkylamines by Photoredox/Nickel-Catalyzed Aminoalkylation of Organohalides DOI
Tao Yang,

Wenhui Xiong,

Guangyu Sun

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(42), P. 29177 - 29188

Published: Oct. 12, 2024

Tertiary alkylamines are privileged structural motifs widely present in natural products, pharmaceutical agents, and bioactive molecules, their efficient synthesis has been a longstanding goal organic chemistry. The functionalization of α-amino radicals derived from abundant precursors represents an emerging approach to accessing alkylamines, but application this strategy obtain tertiary remains challenging. Here, we show that dual photoredox/nickel catalysis enables aminoalkylation organohalides (sp

Language: Английский

Citations

6
Modular synthesis of α-branched secondary alkylamines via visible-light-mediated carbonyl alkylative amination DOI Creative Commons
Milo A. Smith, Ryan Kang, Roopender Kumar

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(36), P. 14888 - 14898

Published: Jan. 1, 2024

A multicomponent method for the synthesis of α-branched secondary alkylamines is described. The provides expedited access to saturated N-heterocycles, and enables selective alkylation primary amines over cyclic amines.

Language: Английский

Citations

5
Photocatalytic Decarboxylative Alkylation of Cyclic Imine–BF3 Complexes: A Modular Route to Functionalized Azacycles DOI
Kamal Bhatt,

Alafate Adili,

Andrew Tran

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

Alkyl radicals generated via an acridine photocatalyzed decarboxylation reaction of feedstock carboxylic acids engage with a range cyclic imine-BF

Language: Английский

Citations

5
Versatile, Modular, and General Strategy for the Synthesis of α-Amino Carbonyls DOI Creative Commons
Jianzhong Liu, Matthew J. Gaunt

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(35), P. 24699 - 24707

Published: Aug. 24, 2024

Modulating the basicity of alkylamines is a crucial factor in drug design. Consequently, with proximal amide, ester, or ketone have become privileged features many pharmaceutical candidates. The impact α-amino carbonyls has made development new methods for their preparation continuous challenge synthesis. Here, we describe practical strategy that provides modular and programmable synthesis wide range carbonyls. generality this process possible by an extremely mild method to generate carbamoyl radicals, proceeding via Lewis acid-visible-light-mediated Norrish type-I fragmentation tailored carboxamide reagent intercepted through addition situ generated unbiased imines. Aside from reaction's broad scope each component, its capacity draw on plentiful diversely populated amine carbonyl feedstocks showcased two-dimensional array used construct library novel, assay-ready, amides.

Language: Английский

Citations

4
Systematic, computational discovery of multicomponent and one-pot reactions DOI Creative Commons
Rafał Roszak, Louis Gadina, Agnieszka Wołos

et al.

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

Published: Nov. 27, 2024

Discovery of new types reactions is essential to organic chemistry because it expands the scope accessible molecular scaffolds and can enable more economical syntheses existing structures. In this context, so-called multicomponent reactions, MCRs, are particular interest they build complex from multiple starting materials in just one step, without purification intermediates. However, for over a century active research, MCRs have been discovered rather than designed, their number remains limited only several hundred. This work demonstrates that computers taught knowledge reaction mechanisms rules physical-organic design – completely autonomously large numbers mechanistically distinct MCRs. Moreover, when supplemented by models approximate kinetic rates, algorithm predict yields identify potential organocatalysis. These predictions validated experiments spanning different modes reactivity diverse product scaffolds. Multi component (MCRs) step intermediates but until now designed. Here, authors demonstrate an algorithmic approach based numbers.

Language: Английский

Citations

3
Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines DOI Creative Commons
Antonio Pulcinella, Stefano Bonciolini, Robin Stuhr

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 22, 2025

Abstract Secondary amines are vital functional groups in pharmaceuticals, agrochemicals, and natural products, necessitating efficient synthetic methods. Traditional approaches, including N -monoalkylation reductive amination, suffer from limitations such as poor chemoselectivity complexity. Herein, we present a streamlined deoxygenative photochemical alkylation of secondary amides, enabling the synthesis α-branched amines. Our method leverages triflic anhydride-mediated semi-reduction amides to imines, followed by radical step. This approach broadens utility facilitating late-stage modifications drug-like molecules saturated -substituted heterocycles. The pivotal role flow technology developing scalable robust process underscores practicality this method, significantly expanding organic chemist’s toolbox for complex amine synthesis.

Language: Английский

Citations

0