General and selective metal-free radical α-C–H borylation of aliphatic amines

Sarkar, Sumon; Wagulde, Sidhant; Jia, Xiangqing; Gevorgyan, Vladimir

doi:10.1016/j.chempr.2022.07.022

Cited by 34 publications

(18 citation statements)

References 92 publications

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“…Among various scenarios, the selective installation of a boryl moiety on C(sp 3 )–H bonds of hydrocarbons constitutes an intriguing frontier of contemporary research since the pivotal role of organoboron compounds as essential building blocks has attracted the attention of both industrial and academic laboratories for decades . Not surprisingly, recent years have witnessed the emergence of several elegant research works on C(sp 3 )–H borylation reactions . A significant breakthrough was recently made by Aggarwal and co-workers, who described a radical-mediated C(sp 3 )–H borylation of hydrocarbons using a photoinduced HAT strategy .…”

Section: Introductionmentioning

confidence: 99%

Iron-Catalyzed C(Sp³)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Guo

et al. 2023

J. Am. Chem. Soc.

104

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Catalytic C(sp 3 )−H functionalization has provided enormous opportunities to construct organic molecules, facilitating the derivatization of complex pharmaceutical compounds. Within this framework, direct hydrogen atom transfer (HAT) photocatalysis becomes an appealing approach to this goal. However, the viable substrates utilized in these protocols are limited, and the site selectivity shows preference to activated and thermodynamically favored C(sp 3 )−H bonds. Herein, we describe the development of undirected iron-catalyzed C(sp 3 )−H borylation, thiolation, and sulfinylation reactions enabled by the photoinduced ligand-to-metal charge transfer (LMCT) process. These reactions exhibit remarkably broad substrate scope (>150 examples in total), and most importantly, all of these three reactions show unconventional regioselectivity, with the occurrence of C(sp 3 )−H borylation, thiolation, and sulfinylation preferentially at the distal methyl position. The procedures are operationally simple and readily scalable and provide access to high-value products from simple hydrocarbons in one step. Mechanistic studies and control experiments indicate that the afforded site selectivity is not only relevant to the HAT species but also largely affected by the use of boron-and sulfone-based radical acceptors.

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Section: Introductionmentioning

confidence: 99%

Iron-Catalyzed C(Sp³)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Guo

et al. 2023

J. Am. Chem. Soc.

104

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“…This means that the subsequent photoinduced LMCT-mediated borylation becomes a redox-neutral process and therefore catalytic in CuCl 2 . To our knowledge, this represents the first report of bis-boryloxides being used as borylating agents for alkyl radicals and could have useful implications in radical-mediated borylation reactions by providing a polarity reversal from commonly used, nucleophilic diboron reagents. ,, …”

Section: Resultsmentioning

confidence: 93%

“…Importantly, substrates that were found to be incompatible under our metal-free conditions, such as ketones, ethers, and cyclic amides, could be successfully borylated using CuCl 2 . Additionally, enhanced regioselectivities were observed for several substrates (7,8,10), although this was not always the case, since some products were formed with comparable (13,47) or lower (6,25,45) regioselectivities.…”

Section: Journal Of the American Chemicalmentioning

confidence: 96%

“…To our knowledge, this represents the first report of bis-boryloxides being used as borylating agents for alkyl radicals and could have useful implications in radical-mediated borylation reactions by providing a polarity reversal from commonly used, nucleophilic diboron reagents. 5,6,17 Substrate Scope. With optimized conditions in hand, the scope of this photoinduced C(sp 3 )−H borylation was explored (Figure 3).…”

Section: Journal Of the American Chemicalmentioning

confidence: 99%

“…The resulting alkyl radical is then intercepted by bis(catecholato)diboron (B 2 cat 2 ) in a homolytic substitution reaction to generate alkyl boronic ester products. This methodology allows challenging C(sp 3 )–H borylations to be performed at ambient temperature and in the absence of metal catalysts; however, the overall oxidative process suffers from poor atom economy due to the necessary use of an N -alkoxyphthalimide as a stoichiometric photo-oxidant. By comparison, precious-metal-catalyzed borylations proceed under oxidant-free conditions because of the ability of the catalysts to undergo oxidative addition and reductive elimination reactions with both the diboron reagent and C–H bonds, which enables them to promote dehydrogenative reactions with the release of dihydrogen gas (H 2 ) (Figure b) .…”

Section: Introductionmentioning

confidence: 99%

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Copper-Mediated Dehydrogenative C(sp³)–H Borylation of Alkanes

et al. 2023

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Borylations of inert carbon–hydrogen bonds are highly useful for transforming feedstock chemicals into versatile organoboron reagents. Catalysis of these reactions has historically relied on precious-metal complexes, which promote dehydrogenative borylations with diboron reagents under oxidant-free conditions. Recently, photoinduced radical-mediated borylations involving hydrogen atom transfer pathways have emerged as attractive alternatives because they provide complimentary regioselectivities and proceed under metal-free conditions. However, these net oxidative processes require stoichiometric oxidants and therefore cannot compete with the high atom economy of their precious-metal-catalyzed counterparts. Herein, we report that CuCl2 catalyzes radical-mediated, dehydrogenative C(sp3)–H borylations of alkanes with bis(catecholato)diboron under oxidant-free conditions. This is a result of an unexpected dual role of the copper catalyst, which promotes oxidation of the diboron reagent to generate an electrophilic bis-boryloxide that acts as an effective borylating agent in subsequent redox-neutral photocatalytic C–H borylations.

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Halogen Bonding Initiated Difunctionalization of [1.1.1]Propellane via Photoinduced Polarity Match Additions

Yi,

Kong,

Prabhakar Kale

et al. 2024

Angewandte Chemie

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Bicyclo[1.1.1]pentane (BCP), recognized as a bioisostere for para‐disubstituted benzene, has gained widespread interest in drug development due to its ability to enhance the physicochemical properties of pharmaceuticals. In this work, we introduce a photoinduced, halogen bonding‐initiated, metal‐free strategy for synthesizing various BCP derivatives. This method involves the generation of nucleophilic α‐aminoalkyl radicals via halogen‐bonding adducts. These undergo selective radical addition to [1.1.1]propellane, yielding electrophilic BCP radicals that subsequently participate in polarity‐matched additions, culminating in the difunctionalization of bicyclopentane. The versatility and practicality of this metal‐free approach are underscored by its broad substrate scope, which includes late‐stage functionalization and a series of valuable transformations, all conducted under mild reaction conditions.

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General and selective metal-free radical α-C–H borylation of aliphatic amines

Cited by 34 publications

References 92 publications

Iron-Catalyzed C(Sp³)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Iron-Catalyzed C(Sp³)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Copper-Mediated Dehydrogenative C(sp³)–H Borylation of Alkanes

Halogen Bonding Initiated Difunctionalization of [1.1.1]Propellane via Photoinduced Polarity Match Additions

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General and selective metal-free radical α-C–H borylation of aliphatic amines

Cited by 34 publications

References 92 publications

Iron-Catalyzed C(Sp3)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Iron-Catalyzed C(Sp3)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Copper-Mediated Dehydrogenative C(sp3)–H Borylation of Alkanes

Halogen Bonding Initiated Difunctionalization of [1.1.1]Propellane via Photoinduced Polarity Match Additions

Contact Info

Product

Resources

About

Iron-Catalyzed C(Sp³)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Iron-Catalyzed C(Sp³)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Copper-Mediated Dehydrogenative C(sp³)–H Borylation of Alkanes