scholarly journals General Electrochemical Minisci Alkylation of N-Heteroarenes with Alkyl Halides

2022 ◽  
Author(s):  
Jose Aleman
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Environmentally Friendly ◽  
Building Blocks ◽  
Alkyl Halides ◽  
Alkyl Radicals ◽  
First Time ◽  
Very High ◽  
Tertiary Alkyl

Abstract Herein, we report, for the first time, a general, facile and environmentally friendly Minisci-type alkylation of N-heteroarenes under simple and straightforward electrochemical conditions using widely available alkyl halides as radical precursors. Primary, secondary and tertiary alkyl radicals have shown to be efficiently generated and coupled with a large variety of N-heteroarenes. The method presents a very high functional group tolerance, including various heterocyclic-based natural products, which highlights the robustness of the methodology. This applicability has been further proved in the synthesis of various interesting biologically valuable building blocks. In addition, we have proposed a mechanism based on different proofs and electrochemical evidences.

scholarly journals Tandem Photoredox Catalysis: Enabling Carbonylative Amidation of Aryl and Alkylhalides

2020 ◽  
Author(s):  
José Augusto Forni ◽  
NENAD MICIC ◽  
Timothy Connell ◽  
GEETHIKA WERAGODA ◽  
Anastasios Polyzos
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Aromatic Amines ◽  
Functional Group ◽  
Alkyl Halides ◽  
Catalytic Cycle ◽  
Aryl Bromides ◽  
Alkyl Iodides ◽  
Tertiary Alkyl

<p>We report a new visible light-mediated carbonylative amidation of aryl, heteroaryl and alkyl halides. A tandem catalytic cycle of [Ir(ppy)<sub>2</sub>(dtb-bpy)]<sup>+</sup> generates a potent iridium photoreductant via a second catalytic cycle in the presence of DIPEA which productively engages aryl bromides, iodides and even chlorides as well as primary, secondary and tertiary alkyl iodides. The versatility of the in-situ generated catalyst is illustrated by compatibility with aliphatic and aromatic amines, high functional group tolerance and the late-stage amidation of complex natural products. </p>

scholarly journals Chiral Alkyl Amine Synthesis via Catalytic Enantioselective Hydroalkylation of Enamides

2020 ◽  
Author(s):  
Deyun Qian ◽  
Srikrishna Bera ◽  
Xile Hu
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Building Blocks ◽  
Alkyl Halides ◽  
Enantioselective Synthesis ◽  
Mild Conditions ◽  
Drug Molecules ◽  
Alkyl Amines ◽  
Wide Range ◽  
Synthetic Intermediates

Chiral alkyl amines are omnipresent as bio-active molecules and synthetic intermediates. Catalytic and enantioselective synthesis of alkyl amines from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble a wide range of chiral alkyl amines from enamides and alkyl halides in high regio- and enantioselectivity. The method works for both non-activated and activated alkyl halides, and is able to produce enantiomerically enriched amines with two minimally differentiated alpha-alkyl substituents. The mild conditions lead to high functional group tolerance, which is demonstrated in the post-product functionalization of many natural products and drug molecules, as well as the synthesis of chiral building blocks and key intermediates to bio-active compounds.

scholarly journals Chiral Alkyl Amine Synthesis via Catalytic Enantioselective Hydroalkylation of Enamides

2020 ◽  
Author(s):  
Deyun Qian ◽  
Srikrishna Bera ◽  
Xile Hu
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Building Blocks ◽  
Alkyl Halides ◽  
Enantioselective Synthesis ◽  
Mild Conditions ◽  
Drug Molecules ◽  
Alkyl Amines ◽  
Wide Range ◽  
Synthetic Intermediates

Chiral alkyl amines are omnipresent as bio-active molecules and synthetic intermediates. Catalytic and enantioselective synthesis of alkyl amines from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble a wide range of chiral alkyl amines from enamides and alkyl halides in high regio- and enantioselectivity. The method works for both non-activated and activated alkyl halides, and is able to produce enantiomerically enriched amines with two minimally differentiated alpha-alkyl substituents. The mild conditions lead to high functional group tolerance, which is demonstrated in the post-product functionalization of many natural products and drug molecules, as well as the synthesis of chiral building blocks and key intermediates to bio-active compounds.

scholarly journals Tandem Photoredox Catalysis: Enabling Carbonylative Amidation of Aryl and Alkylhalides

2020 ◽  
Author(s):  
José Augusto Forni ◽  
NENAD MICIC ◽  
Timothy Connell ◽  
GEETHIKA WERAGODA ◽  
Anastasios Polyzos
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Aromatic Amines ◽  
Functional Group ◽  
Alkyl Halides ◽  
Catalytic Cycle ◽  
Aryl Bromides ◽  
Alkyl Iodides ◽  
Tertiary Alkyl

<p>We report a new visible light-mediated carbonylative amidation of aryl, heteroaryl and alkyl halides. A tandem catalytic cycle of [Ir(ppy)<sub>2</sub>(dtb-bpy)]<sup>+</sup> generates a potent iridium photoreductant via a second catalytic cycle in the presence of DIPEA which productively engages aryl bromides, iodides and even chlorides as well as primary, secondary and tertiary alkyl iodides. The versatility of the in-situ generated catalyst is illustrated by compatibility with aliphatic and aromatic amines, high functional group tolerance and the late-stage amidation of complex natural products. </p>

scholarly journals Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Chi Wai Cheung ◽  
Xile Hu
Keyword(s):  
Organic Molecules ◽  
Functional Group ◽  
Iron Catalyst ◽  
Alkyl Halides ◽  
Mechanistic Study ◽  
Reductive Coupling ◽  
Alkyl Radicals ◽  
Aryl Amines ◽  
Tertiary Alkyl ◽  
General Method

Abstract (Hetero)Aryl amines, an important class of organic molecules in medicinal chemistry, are most commonly synthesized from anilines, which are in turn synthesized by hydrogenation of nitroarenes. Amine synthesis directly from nitroarenes is attractive due to improved step economy and functional group compatibility. Despite these potential advantages, there is yet no general method for the synthesis of (hetero)aryl amines by carbon–nitrogen cross-coupling of nitroarenes. Here we report the reductive coupling of nitroarenes with alkyl halides to yield (hetero)aryl amines. A simple iron catalyst enables the coupling with numerous primary, secondary and tertiary alkyl halides. Broad scope and high functional group tolerance are demonstrated. Mechanistic study suggests that nitrosoarenes and alkyl radicals are involved as intermediates. This new C–N coupling method provides general and step-economical access to aryl amines.

scholarly journals Enantioselective Access to Dialkyl Amines and Alcohols via Ni-Catalyzed Reductive Hydroalkylations

2021 ◽  
Author(s):  
Shan Wang ◽  
Tian-Yi Zhang ◽  
Jian-Xin Zhang ◽  
Huan Meng ◽  
Bi-Hong Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Alkyl Halides ◽  
Aliphatic Amines ◽  
Fine Chemicals ◽  
Alkyl Groups ◽  
Simple Protocol ◽  
Enol Esters

Abstract Chiral dialkyl amines and alcohols are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective reductive hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic amines and alcohols in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral dialkyl amine and alcohol derivatives from simple starting materials with great functional group tolerance.

Ni-catalyzed reductive addition of alkyl halides to isocyanides

2015 ◽  
Vol 13 (47) ◽  
pp. 11418-11421 ◽  
Author(s):  
Bo Wang ◽  
Yijing Dai ◽  
Weiqi Tong ◽  
Hegui Gong
Keyword(s):  
Alkyl Halides ◽  
Carbene Ligands ◽  
Alkyl Radicals ◽  
Tertiary Alkyl

This work emphasizes Ni-catalyzed reductive trapping of secondary and tertiary alkyl radicals with both aryl isocyanides affording 6-alkylated phenanthridine in good yields. The employment of carbene ligands represents the examples of generation of alkyl radicals from the halide precursors under Ni-catalyzed reductive conditions.

scholarly journals Enantioselective Access to Dialkyl Amines and Alcohols via Ni-Catalyzed Reductive Hydroalkylations

2020 ◽  
Author(s):  
Shan Wang ◽  
Tian-Yi Zhang ◽  
Jian-Xin Zhang ◽  
Huan Meng ◽  
Bi-Hong Chen
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Alkyl Halides ◽  
Aliphatic Amines ◽  
Fine Chemicals ◽  
Alkyl Groups ◽  
Simple Protocol

Chiral dialkyl amines and alcohols are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective reductive hydroalkylation of enamides and enolates with alkyl halides to afford enantioenriched α-branched aliphatic amines and alcohols in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral dialkyl amine and alcohol derivatives from simple starting materials with great functional group tolerance.

Alkoxyallenes as Starting Materials for the Syntheses of Natural Products

2020 ◽  
Vol 23 (27) ◽  
pp. 2976-3003 ◽  
Author(s):  
Volker Martin Schmiedel ◽  
Hans-Ulrich Reissig
Keyword(s):  
Natural Products ◽  
Carbonyl Compounds ◽  
Building Blocks ◽  
Alkyl Halides ◽  
Natural Product Synthesis ◽  
Subsequent Reaction ◽  
Enol Ethers ◽  
Carbocyclic Compounds ◽  
Nazarov Cyclizations ◽  
High Stereoselectivity

Alkoxyallenes are easily available and versatile building blocks for the preparation of a variety of natural products (terpenes, polyketides, alkaloids, amino acids, carbohydrates etc.) originating from different classes. The synthetic use of the three allene carbon atoms frequently follows the “normal” reactivity pattern showing that alkoxyallenes can be regarded as special enol ethers. Additions of alcohols or amines to alkoxyallenes form vinyl-substituted O,O- or N,O-acetals that are frequently used in ring-closing metathesis reactions. This methodology delivers crucial heterocyclic units of the target compounds. Enantioselective additions provide products with high enantiopurity. Alternatively, an “Umpolung” of reactivity of alkoxyallenes is achieved by lithiation at C-1 and subsequent reaction with electrophiles, such as alkyl halides, carbonyl compounds, imines or nitrones. High stereoselectivity of the addition step can be achieved by substrate control or auxiliary control. The high diastereo- or enantioselectivity is transferred to the subsequent acyclic or cyclic products. The cyclization of primary addition products occurs efficiently under mild conditions and provides functionalized dihydrofuran, dihydropyrrole or 1,2-oxazine derivatives. These are valuable intermediates for the synthesis of a variety of heterocyclic natural products. Nazarov cyclizations or gold catalyzed rearrangements allow the synthesis of five- and six-membered carbocyclic compounds that are also used for natural product synthesis. Dedicated to Dr. Reinhold Zimmer, a pioneer of alkoxyallene chemistry, on the occasion of his 60th birthday.

scholarly journals Boron: A key element in radical reactions

2007 ◽  
Vol 79 (2) ◽  
pp. 223-233 ◽  
Author(s):  
Philippe Renaud ◽  
Alice Beauseigneur ◽  
Andrea Brecht-Forster ◽  
Barbara Becattini ◽  
Vincent Darmency ◽  
...  
Keyword(s):  
Chain Transfer ◽  
High Sensitivity ◽  
Conjugate Addition ◽  
Radical Reactions ◽  
Radical Chain ◽  
Alkyl Radicals ◽  
Wide Range ◽  
A Chain ◽  
Very High ◽  
Tertiary Alkyl

Boron derivatives are becoming key reagents in radical chemistry. Here, we describe reactions where an organoboron derivative is used as a radical initiator, a chain-transfer reagent, and a radical precursor. For instance, B-alkylcatecholboranes, easily prepared by hydroboration of alkenes, represent a very efficient source of primary, secondary, and tertiary alkyl radicals. Their very high sensitivity toward oxygen- and heteroatom-centered radicals makes them particularly attractive for the development of radical chain processes such as conjugate addition, allylation, alkenylation, and alkynylation. Boron derivatives have also been used to develop an attractive new procedure for the reduction of radicals with alcohols and water. The selected examples presented here demonstrate that boron-containing reagents can efficiently replace tin derivatives in a wide range of radical reactions.

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