Advances in C(sp3)–H Bond Functionalization via Radical Processes

Synthesis ◽  
2019 ◽  
Vol 51 (24) ◽  
pp. 4531-4548 ◽  
Author(s):  
Tong Zhang ◽  
Yue-Hua Wu ◽  
Nai-Xing Wang ◽  
Yalan Xing
Keyword(s):  
Free Radicals ◽  
Hydrogen Atom ◽  
Functional Groups ◽  
Organic Molecules ◽  
Functional Group ◽  
Hydrogen Atom Transfer ◽  
Significant Progress ◽  
Bond Functionalization ◽  
Direct Functionalization ◽  
Radical Processes

C(sp3)–H Bonds are the most common structures in organic molecules. In recent years, the direct functionalization of C(sp3)–H bonds has attracted wide attention and made significant progress. This review mainly focuses on C(sp3)–H bond functionalization of alkanes with or without functional groups via radical processes reported since 2017. In particular, three methods of generating free radicals are discussed: the use of a radical initiator such as TBHP or DTBP; photocatalysis, and via 1,5-hydrogen atom transfer (1,5-HAT).1 Introduction2 C(sp3)–H Bond Functionalization of Alkanes3 C(sp3)–H Bond Functionalization of Alkanes with a Functional Group4 Conclusions

scholarly journals Photo-induced copper-catalyzed sequential 1,n-HAT enabling the formation of cyclobutanols

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhusong Cao ◽  
Jianye Li ◽  
Guozhu Zhang
Keyword(s):  
Natural Products ◽  
Hydrogen Atom ◽  
Functional Groups ◽  
Organic Synthesis ◽  
Copper Complex ◽  
Building Blocks ◽  
Hydrogen Atom Transfer ◽  
Efficient Synthesis ◽  
Bond Functionalization ◽  
Cascade Cyclization

AbstractCyclobutanols are privileged cyclic skeletons in natural products and synthetic building blocks. C(sp3)−H functionalization is a prolonged challenge in organic synthesis. The synthesis of cyclobutanols through double C(sp3)-H bond functionalization remains elusive. Here we report the efficient synthesis of cyclobutanols through intermolecular radical [3 + 1] cascade cyclization, involving the functionalization of two C − H bonds through sequential hydrogen atom transfer. The copper complex reduces the iodomethylsilyl alcohols efficiently under blue-light irradiation to initiate the tandem transformation. The mild reaction tolerates a broad range of functional groups and allows for the facile generation of elaborate polycyclic structures.

Catalytic Synthesis of Cyclic Guanidines via Hydrogen Atom Transfer and Radical-Polar Crossover

2020 ◽  
Author(s):  
Shunya Ohuchi ◽  
Hiroki Koyama ◽  
Hiroki Shigehisa
Keyword(s):  
Hydrogen Atom ◽  
Functional Group ◽  
Hydrogen Atom Transfer ◽  
Catalytic Synthesis ◽  
Membered Ring ◽  
Biologically Active ◽  
Atom Transfer ◽  
Powerful Method ◽  
Protective Groups ◽  
The Common

A catalytic synthesis of cyclic guanidines, which are found in many biologically active compounds and natu-ral products, was developed, wherein transition-metal hydrogen atom transfer and radical-polar crossover were employed. This mild and functional-group tolerant process enabled the cyclization of alkenyl guanidines bearing common protective groups, such as Cbz and Boc. This powerful method not only provided the common 5- and 6-membered rings but also an unusual 7-membered ring. The derivatization of the products afforded various heterocycles. We also investigated the se-lective cyclization of mono-protected or hetero-protected (TFA and Boc) alkenyl guanidines and their further derivatiza-tions.

Regioselective C(sp3)–H alkylation of a fructopyranose derivative by 1,6-HAT

2021 ◽  
Vol 19 (14) ◽  
pp. 3124-3127
Author(s):  
Yanru Li ◽  
Shoto Miyamoto ◽  
Takeru Torigoe ◽  
Yoichiro Kuninobu
Keyword(s):  
Hydrogen Atom ◽  
Functional Groups ◽  
Hydrogen Atom Transfer ◽  
Atom Transfer

We developed regioselective C(sp3)–H alkylation of a fructopyranose derivative, which enables the introduction of several functional groups, by 1,6-hydrogen atom transfer.

scholarly journals Site-Selective A-C-H Functionalization of Trialkylamines via Reversible Hydrogen Atom Transfer Catalysis

2021 ◽  
Author(s):  
Yangyang Shen ◽  
Franziska Schoenebeck ◽  
Ignacio Funes-Ardoiz ◽  
Tomislav Rovis
Keyword(s):  
Drug Discovery ◽  
Hydrogen Atom ◽  
Late Stage ◽  
Hydrogen Atom Transfer ◽  
Atom Transfer ◽  
Bond Functionalization ◽  
Carbon Centers ◽  
Radical Trapping ◽  
Site Selectivity ◽  
Site Selective

Trialkylamines are widely found in naturally-occurring alkaloids, synthetic agrochemicals, biological probes, and especially pharmaceuticals agents and pre-clinical candidates. Despite the recent breakthrough of catalytic alkylation of dialkylamines, the selective a-C(sp3 )–H bond functionalization of widely available trialkylamine scaffolds holds promise to streamline complex trialkylamine synthesis, accelerate drug discovery and execute late-stage pharmaceutical modification with complementary reactivity. However, the canonical methods always result in functionalization at the less-crowded site. Herein, we describe a solution to switch the reaction site through fundamentally overcoming the steric control that dominates such processes. By rapidly establishing an equilibrium between a-amino C(sp3 )-H bonds and a highly electrophilic thiol radical via reversible hydrogen atom transfer, we leverage a slower radical-trapping step with electron-deficient olefins to selectively forge a C(sp3 )-C(sp3 ) bond with the more-crowded a-amino radical, with the overall selectivity guided by Curtin-Hammett principle. This subtle reaction profile has unlocked a new strategic concept in direct C-H functionalization arena for forging C– C bonds from a diverse set of trialkylamines with high levels of site-selectivity and preparative utility. Simple correlation of site-selectivity and 13C NMR shift serves as a qualitative predictive guide. The broad consequences of this dynamic system, together with the ability to forge N-substituted quaternary carbon centers and implement late-stage functionalization techniques, holds tremendous potential to streamline complex trialkylamine synthesis and accelerate drug discovery

scholarly journals C–H functionalization reactions enabled by hydrogen atom transfer to carbon-centered radicals

2020 ◽  
Vol 11 (48) ◽  
pp. 12974-12993
Author(s):  
Sumon Sarkar ◽  
Kelvin Pak Shing Cheung ◽  
Vladimir Gevorgyan
Keyword(s):  
Hydrogen Atom ◽  
Organic Molecules ◽  
Hydrogen Atom Transfer ◽  
Atom Transfer

Intramolecular and intermolecular HAT to C-centered radicals enables selective C–H functionalization of organic molecules.

1.13 Intramolecular Hydrogen-Atom Transfer

2021 ◽  
Author(s):  
S. Treacy ◽  
X. Zhang ◽  
T. Rovis
Keyword(s):  
Hydrogen Atom ◽  
Functional Groups ◽  
Open Shell ◽  
Hydrogen Atom Transfer ◽  
Atom Transfer ◽  
Stable Carbon ◽  
Radical Reactivity ◽  
Recent Advances ◽  
Synthetic Chemist ◽  
Intramolecular Hydrogen

AbstractRecent advances in intramolecular hydrogen-atom transfer (HAT) have demonstrated significant utility in C—H functionalization through highly reactive open-shell intermediates. The intramolecular transposition of radical reactivity from select functional groups to generate more stable carbon-centered radicals often proceeds with high regioselectivity, providing novel bond disconnections at otherwise inert and largely indistinguishable positions. This chapter explores the functional groups capable of intramolecular HAT to generate remote radicals and the transformations currently available to the synthetic chemist.

scholarly journals A Bond-Weakening Borinate Catalyst that Improves the Scope of the Photoredox α-C–H Alkylation of Alcohols

Synthesis ◽  
2020 ◽  
Vol 52 (15) ◽  
pp. 2171-2189
Author(s):  
Kounosuke Oisaki ◽  
Motomu Kanai ◽  
Kentaro Sakai
Keyword(s):  
Hydrogen Atom ◽  
Visible Light ◽  
Organic Synthesis ◽  
Hydroxy Group ◽  
Functional Group ◽  
Chemical Yield ◽  
Catalyst System ◽  
Hydrogen Atom Transfer ◽  
Hybrid Catalyst ◽  
Site Selective

The development of catalyst-controlled, site-selective C(sp3)–H functionalization reactions is currently a major challenge in organic synthesis. In this paper, a novel bond-weakening catalyst that recognizes the hydroxy group of alcohols through formation of a borate is described. An electron-deficient borinic acid–ethanolamine complex enhances the chemical yield of the α-C–H alkylation of alcohols when used in conjunction with a photoredox catalyst and a hydrogen atom transfer catalyst under irradiation with visible light. This ternary hybrid catalyst system can, for example, be applied to functional-group-enriched­ peptides.

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