Stannylated allyl carbonates as versatile building blocks for the diversity oriented synthesis of allylic amines and amides

Allylic amines are valuable synthetic targets en route to diverse biologically active amine products. Current allylic C–H amination strate-gies remain limited with respect to the viable N-substituents. Herein we disclose a new electrochemical process to prepare aliphatic allylic amines by coupling two abundant starting materials: secondary amines and unactivated alkenes. This oxidative transformation proceeds via electrochemical generation of an electrophilic adduct between thianthrene and the alkene substrates. Treatment of these adducts with aliphatic amine nucleophiles and base provides allylic amine products in high yield. This synthetic strategy is also amenable to functionali-zation of feedstock gaseous alkenes at 1 atmosphere. In the case of 1-butene, remarkable Z-selective crotylation is observed. This strategy, however, is not limited to the synthesis of simple building blocks; complex biologically active molecules are suitable as both alkene and amine coupling partners. Preliminary mechanistic studies implicate vinylthianthrenium salts as key reactive intermediates.

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Diversity-Oriented Synthesis: Amino Acetophenones as Building Blocks for the Synthesis of Natural Product Analogs

Pharmaceuticals ◽

10.3390/ph14111127 ◽

2021 ◽

Vol 14 (11) ◽

pp. 1127

Author(s):

Mathias Eymery ◽

Viet-Khoa Tran-Nguyen ◽

Ahcène Boumendjel

Keyword(s):

Drug Discovery ◽

Natural Product ◽

Organic Synthesis ◽

Building Blocks ◽

Structural Features ◽

The Other ◽

Pharmacological Properties ◽

Diversity Oriented Synthesis ◽

Fully Integrated ◽

Lead Compounds

Diversity-Oriented Synthesis (DOS) represents a strategy to obtain molecule libraries with diverse structural features starting from one common compound in limited steps of synthesis. During the last two decades, DOS has become an unmissable strategy in organic synthesis and is fully integrated in various drug discovery processes. On the other hand, natural products with multiple relevant pharmacological properties have been extensively investigated as scaffolds for ligand-based drug design. In this article, we report the amino dimethoxyacetophenones that can be easily synthesized and scaled up from the commercially available 3,5-dimethoxyaniline as valuable starting blocks for the DOS of natural product analogs. More focus is placed on the synthesis of analogs of flavones, coumarins, azocanes, chalcones, and aurones, which are frequently studied as lead compounds in drug discovery.

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Site-Selective Allylic C-H Amination with Aliphatic Amines

10.21203/rs.3.rs-270473/v1 ◽

2021 ◽

Author(s):

Shengchun Wang ◽

Yiming Gao ◽

Demin Ren ◽

He Sun ◽

Linbin Niu ◽

...

Keyword(s):

Hydrogen Atom ◽

Building Blocks ◽

Hydrogen Atom Transfer ◽

Allylic Amines ◽

Allylic Amination ◽

Alkyl Amines ◽

Reaction Proceeds ◽

Bond Options ◽

A Site ◽

Site Selective

Abstract The direct coupling of olefins and alkyl amines represents the most efficient and atom-economical approach to prepare aliphatic allylamines which are fundamental building blocks. However, the method that achieves this goal while exhibiting exquisite control over the site at which the amine is introduced remains elusive. Herein, we report that the combination of a photocatalyst and a cobaloxime enables site-selective allylic C–H amination of olefins with secondary alkyl amines to afford allylic amines, eliminating the need for oxidants. This reaction proceeds by a radical-based mechanism distinct from those of existing allylic amination reactions. It affords the product resulting from cleavage of the stronger, primary allylic C–H bonds over other weaker allylic C–H bond options. DFT calculations reveal that this selectivity originates from a cobaloxime-promoted hydrogen atom transfer (HAT) process. Our method is compatible with a broad scope of alkenes, and can be extended to achieve a site- and diastereoselective amination of natural terpenes.

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An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.13.110 ◽

2017 ◽

Vol 13 ◽

pp. 1106-1118 ◽

Cited By ~ 7

Author(s):

Sushil K Maurya ◽

Rohit Rana

Keyword(s):

Building Blocks ◽

Ring Size ◽

Macrocyclic Compounds ◽

Reaction Conditions ◽

Structural Class ◽

Diversity Oriented Synthesis ◽

Cuaac Reaction ◽

Standard Reaction

An efficient, eco-compatible diversity-oriented synthesis (DOS) approach for the generation of library of sugar embedded macrocyclic compounds with various ring size containing 1,2,3-triazole has been developed. This concise strategy involves the iterative use of readily available sugar-derived alkyne/azide–alkene building blocks coupled through copper catalyzed azide–alkyne cycloaddition (CuAAC) reaction followed by pairing of the linear cyclo-adduct using greener reaction conditions. The eco-compatibility, mild reaction conditions, greener solvents, easy purification and avoidance of hazards and toxic solvents are advantages of this protocol to access this important structural class. The diversity of the macrocycles synthesized (in total we have synthesized 13 macrocycles) using a set of standard reaction protocols demonstrate the potential of the new eco-compatible approach for the macrocyclic library generation.

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Microwave-assisted preparation of 4-amino-3-cyano-5-methoxycarbonyl-N-arylpyrazoles as building blocks for the diversity-oriented synthesis of pyrazole-based polycyclic scaffolds

Organic & Biomolecular Chemistry ◽

10.1039/c4ob01951b ◽

2015 ◽

Vol 13 (2) ◽

pp. 409-423 ◽

Cited By ~ 17

Author(s):

Laurent Le Corre ◽

Lotfi Tak-Tak ◽

Arthur Guillard ◽

Guillaume Prestat ◽

Christine Gravier-Pelletier ◽

...

Keyword(s):

Building Blocks ◽

Diversity Oriented Synthesis ◽

Microwave Assisted

The obtention of 4-amino-3-cyano-N-arylpyrazoles via a μW mediated cyclization allowed the diversity oriented syntheses of various heteroyclic scaffolds.

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Allylic Amines as Key Building Blocks in the Synthesis of (E)-Alkene Peptide Isosteres

Organic Process Research & Development ◽

10.1021/op2002613 ◽

2012 ◽

Vol 16 (1) ◽

pp. 26-34 ◽

Cited By ~ 60

Author(s):

Erin M. Skoda ◽

Gary C. Davis ◽

Peter Wipf

Keyword(s):

Building Blocks ◽

Allylic Amines ◽

Peptide Isosteres

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Acetic Anhydride–Acetic Acid as a New Dehydrating Agent of Aldoximes for the Preparation of Nitriles: Preparation of 2-Cyanoglycals

Synlett ◽

10.1055/s-0040-1708007 ◽

2020 ◽

Vol 31 (10) ◽

pp. 991-996

Author(s):

Henok H. Kinfe ◽

Tommy F. Mabasa ◽

Jackie Mabasa ◽

Mthokozisi Simelane ◽

Banele Vatsha ◽

...

Keyword(s):

Acetic Acid ◽

Acetic Anhydride ◽

Building Blocks ◽

Reaction Rates ◽

Diversity Oriented Synthesis

Glycals, 1,2-unsatrated carbohydrates, are versatile building blocks for the synthesis of various scaffolds. Despite their potential to serve as suitable precursors in diversity-oriented synthesis, 2-cyanoglycals are less explored in terms of their synthesis and derivatization. Herein, we report a combination of Ac2O and AcOH as new and efficient dehydrating agent of aldoximes for the synthesis of 2-cyanoglycals. In comparison to the conventional dehydrating system of Ac2O-base (such as NaOH, NaOAc and K2CO3), the current protocol provides superior yields and faster reaction rates. The scope and limitations of the dehydrating system are investigated.

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Carbohydrates in diversity-oriented synthesis: challenges and opportunities

Organic & Biomolecular Chemistry ◽

10.1039/c5ob02253c ◽

2016 ◽

Vol 14 (3) ◽

pp. 808-825 ◽

Cited By ~ 29

Author(s):

E. Lenci ◽

G. Menchi ◽

A. Trabocchi

Keyword(s):

Functional Groups ◽

Building Blocks ◽

High Density ◽

Diversity Oriented Synthesis ◽

Challenges And Opportunities ◽

Polar Functional Groups

Carbohydrates are attractive building blocks for diversity-oriented synthesis due to their stereochemical diversity and high density of polar functional groups.

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