scholarly journals A General Strategy for C(sp3)–H Functionalization with Nucleophiles Using Methyl Radical as a Hydrogen Atom Abstractor

2021 ◽  
Author(s):  
Isabelle Leibler ◽  
Makeda A. Tekle-Smith ◽  
Abigail Doyle
Keyword(s):  
Low Cost ◽  
Bioactive Molecules ◽  
General Strategy ◽  
Mechanistic Studies ◽  
Methyl Radical ◽  
Radical Oxidation ◽  
Linear Free Energy ◽  
Carbon Carbon Bond ◽  
Site Selectivity ◽  
Energy Relationships

We have developed a photocatalytic method that employs widely available, low-cost nucleophiles and a readily accessible HAT precursor for C(sp<sup>3</sup>)–H fluorination, chlorination, etherification, thioetherification, azidation, and carbon–carbon bond formation. Mechanistic studies are consistent with methyl radical-mediated HAT and linear free-energy relationships suggest that radical oxidation influences site-selectivity. Furthermore, this approach was highly effective for the construction of multi-halogenated scaffolds and the late-stage functionalization of several bioactive molecules and pharmaceuticals with tunable regioselectivity.

scholarly journals A General Strategy for C(sp3)–H Functionalization with Nucleophiles Using Methyl Radical as a Hydrogen Atom Abstractor

2021 ◽  
Author(s):  
Isabelle Leibler ◽  
Makeda A. Tekle-Smith ◽  
Abigail Doyle
Keyword(s):  
Low Cost ◽  
Bioactive Molecules ◽  
General Strategy ◽  
Mechanistic Studies ◽  
Methyl Radical ◽  
Radical Oxidation ◽  
Linear Free Energy ◽  
Carbon Carbon Bond ◽  
Site Selectivity ◽  
Energy Relationships

We have developed a photocatalytic method that employs widely available, low-cost nucleophiles and a readily accessible HAT precursor for C(sp<sup>3</sup>)–H fluorination, chlorination, etherification, thioetherification, azidation, and carbon–carbon bond formation. Mechanistic studies are consistent with methyl radical-mediated HAT and linear free-energy relationships suggest that radical oxidation influences site-selectivity. Furthermore, this approach was highly effective for the construction of multi-halogenated scaffolds and the late-stage functionalization of several bioactive molecules and pharmaceuticals with tunable regioselectivity.

scholarly journals A general strategy for C(sp3)–H functionalization with nucleophiles using methyl radical as a hydrogen atom abstractor

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Isabelle Nathalie-Marie Leibler ◽  
Makeda A. Tekle-Smith ◽  
Abigail G. Doyle
Keyword(s):  
Hydrogen Atom ◽  
Hydrogen Atom Transfer ◽  
General Strategy ◽  
Photoredox Catalysis ◽  
Mechanistic Studies ◽  
Methyl Radical ◽  
Site Selectivity ◽  
Carbon Centered Radical ◽  
Electrophilic Reagents ◽  
Nucleophilic Reagents

AbstractPhotoredox catalysis has provided many approaches to C(sp3)–H functionalization that enable selective oxidation and C(sp3)–C bond formation via the intermediacy of a carbon-centered radical. While highly enabling, functionalization of the carbon-centered radical is largely mediated by electrophilic reagents. Notably, nucleophilic reagents represent an abundant and practical reagent class, motivating the interest in developing a general C(sp3)–H functionalization strategy with nucleophiles. Here we describe a strategy that transforms C(sp3)–H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radical-polar crossover. The resulting carbocation is functionalized by a variety of nucleophiles—including halides, water, alcohols, thiols, an electron-rich arene, and an azide—to effect diverse bond formations. Mechanistic studies indicate that HAT is mediated by methyl radical—a previously unexplored HAT agent with differing polarity to many of those used in photoredox catalysis—enabling new site-selectivity for late-stage C(sp3)–H functionalization.

Visible-Light Photosensitized Aryl and Alkyl Decarboxylative Carbon-Heteroatom and Carbon-Carbon Bond Formations

2019 ◽  
Author(s):  
Tuhin Patra ◽  
Satobhisha Mukherjee ◽  
Jiajia Ma ◽  
Felix Strieth-Kalthoff ◽  
Frank Glorius
Keyword(s):  
Energy Transfer ◽  
Visible Light ◽  
Alkyl Radical ◽  
General Strategy ◽  
Alkyl Radicals ◽  
Bond Forming ◽  
Radical Trapping ◽  
Carbon Carbon Bond ◽  
Radical Generation ◽  
Trapping Agent

<sub>A general strategy to access both aryl and alkyl radicals by photosensitized decarboxylation of the corresponding carboxylic acids esters has been developed. An energy transfer mediated homolysis of unsymmetrical sigma-bonds for a concerted fragmentation/decarboxylation process is involved. As a result, an independent aryl/alkyl radical generation step enables a series of key C-X and C-C bond forming reactions by simply changing the radical trapping agent.</sub>

Microwave-accelerated Carbon-carbon and Carbon-heteroatom Bond Formation via Multi-component Reactions: A Brief Overview

2020 ◽  
Vol 7 (1) ◽  
pp. 23-39 ◽  
Author(s):  
Kantharaju Kamanna ◽  
Santosh Y. Khatavi
Keyword(s):  
Organic Synthesis ◽  
Bond Formation ◽  
Cycloaddition Reaction ◽  
Nanoparticle Synthesis ◽  
Single Step ◽  
Bioactive Molecules ◽  
One Pot ◽  
Bond Forming ◽  
Material Interest ◽  
Carbon Carbon Bond

Multi-Component Reactions (MCRs) have emerged as an excellent tool in organic chemistry for the synthesis of various bioactive molecules. Among these, one-pot MCRs are included, in which organic reactants react with domino in a single-step process. This has become an alternative platform for the organic chemists, because of their simple operation, less purification methods, no side product and faster reaction time. One of the important applications of the MCRs can be drawn in carbon- carbon (C-C) and carbon-heteroatom (C-X; X = N, O, S) bond formation, which is extensively used by the organic chemists to generate bioactive or useful material synthesis. Some of the key carbon- carbon bond forming reactions are Grignard, Wittig, Enolate alkylation, Aldol, Claisen condensation, Michael and more organic reactions. Alternatively, carbon-heteroatoms containing C-N, C-O, and C-S bond are also found more important and present in various heterocyclic compounds, which are of biological, pharmaceutical, and material interest. Thus, there is a clear scope for the discovery and development of cleaner reaction, faster reaction rate, atom economy and efficient one-pot synthesis for sustainable production of diverse and structurally complex organic molecules. Reactions that required hours to run completely in a conventional method can now be carried out within minutes. Thus, the application of microwave (MW) radiation in organic synthesis has become more promising considerable amount in resource-friendly and eco-friendly processes. The technique of microwaveassisted organic synthesis (MAOS) has successfully been employed in various material syntheses, such as transition metal-catalyzed cross-coupling, dipolar cycloaddition reaction, biomolecule synthesis, polymer formation, and the nanoparticle synthesis. The application of the microwave-technique in carbon-carbon and carbon-heteroatom bond formations via MCRs with major reported literature examples are discussed in this review.

Additive-multiplicative description of extrathermodynamic relations: Application to solvent effect

1990 ◽  
Vol 55 (3) ◽  
pp. 634-643 ◽  
Author(s):  
Oldřich Pytela
Keyword(s):  
Solvent Effect ◽  
Additive Model ◽  
Multiplicative Model ◽  
Data Matrix ◽  
Statistical Parameters ◽  
Model Application ◽  
Mutual Correlation ◽  
Linear Free Energy ◽  
Cross Terms ◽  
Energy Relationships

The paper is focused on evaluation of significance of the additive-multiplicative model of extrathermodynamic relations (linear free energy relationships) as compared with the additive model. Application of the method of conjugated deviations to a data matrix describing manifestations of solvent effects in 367 processes in solutions (6 334 data) has shown that introduction of cross-terms into the additive model is statistically significant for a model with two and particularly three parameters. At the same time the calculation has provided a new set of statistical parameters for description of solvent effect with application of the additive-multiplicative model. Compared with an analogous set designated for the additive model, the new parameters show a lower mutual correlation, retaining the same nature of the properties described, i.e. polarity-acidity (PAC parameter), polarity-basicity (PBC), and polarity-polarizability (PPC).

scholarly journals Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianke Su ◽  
Xinyuan Hu ◽  
Hua Huang ◽  
Yu Guo ◽  
Qiuling Song
Keyword(s):  
Fluorine Atom ◽  
High Efficiency ◽  
Addition Reaction ◽  
Bond Cleavage ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
General Strategy ◽  
Michael Addition Reaction ◽  
Fundamental Properties ◽  
Synthetic Approaches

Abstract2-Fluoroindoles as an important structural scaffold are widely existing in many bioactive or therapeutic agents. Despite their potential usefulness, efficient constructions of 2-fluoroindole derivatives are very sparce. The development of straightforward synthetic approaches to access 2-fluoroindoles is highly desirable for studying their fundamental properties and applications. Herein, we report an efficient and general strategy for the construction of 2-fluoroindoles in which a wide variety of 2-fluoroindoles were accessed with high efficiency and chemoselectivity. Instead of starting from indole skeletons, our strategy constructs indole scaffolds alongside the incorporation of fluorine atom on C2 position in a formal [4+1] cyclization from readily accessible ortho-vinylanilines and difluorocarbene. In our protocol, commercially accessible halodifluoroalkylative reagents provide one carbon and one fluorine atom by cleaving one C-N tertiary bond and forming one C-N bond and one C-C double bond with ortho-vinylanilines. Downstream transformations on 2-fluoroindoles lead to various valuable bioactive molecules which demonstrated significant synthetic advantages over previous reports. And mechanistic studies suggest that the reaction undergoes a cascade difluorocarbene-trapping and intramolecular Michael addition reaction followed by Csp3-F bond cleavage.

scholarly journals Photocatalytic three-component asymmetric sulfonylation via direct C(sp3)-H functionalization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shi Cao ◽  
Wei Hong ◽  
Ziqi Ye ◽  
Lei Gong
Keyword(s):  
Asymmetric Catalysis ◽  
Organic Synthesis ◽  
Photochemical Reaction ◽  
Low Cost ◽  
Bioactive Molecules ◽  
Atom Economy ◽  
Mild Conditions ◽  
Wide Range ◽  
Unsaturated Carbonyl Compound ◽  
Direct Functionalization

AbstractThe direct and selective C(sp3)-H functionalization of cycloalkanes and alkanes is a highly useful process in organic synthesis owing to the low-cost starting materials, the high step and atom economy. Its application to asymmetric catalysis, however, has been scarcely explored. Herein, we disclose our effort toward this goal by incorporation of dual asymmetric photocatalysis by a chiral nickel catalyst and a commercially available organophotocatalyst with a radical relay strategy through sulfur dioxide insertion. Such design leads to the development of three-component asymmetric sulfonylation involving direct functionalization of cycloalkanes, alkanes, toluene derivatives or ethers. The photochemical reaction of a C(sp3)-H precursor, a SO2 surrogate and a common α,β-unsaturated carbonyl compound proceeds smoothly under mild conditions, delivering a wide range of biologically interesting α-C chiral sulfones with high regio- and enantioselectivity (>50 examples, up to >50:1 rr and 95% ee). This method is applicable to late-stage functionalization of bioactive molecules, and provides an appealing access to enantioenriched compounds starting from the abundant hydrocarbon compounds.

scholarly journals PCl3-mediated transesterification and aminolysis of tert-butyl esters via acid chloride formation

2021 ◽  
pp. 174751982098753
Author(s):  
Xiaofang Wu ◽  
Lei Zhou ◽  
Fangshao Li ◽  
Jing Xiao
Keyword(s):  
Acid Chloride ◽  
Bioactive Molecules ◽  
Mechanistic Studies ◽  
One Pot ◽  
Tert Butyl ◽  
Butyl Esters

A PCl3-mediated conversion of tert-butyl esters into esters and amides in one-pot under air is developed. This novel protocol is highlighted by the synthesis of skeletons of bioactive molecules and gram-scale reactions. Mechanistic studies revealed that this transformation involves the formation of an acid chloride in situ, which is followed by reactions with alcohols or amines to afford the desired products.

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