Simple Molecules, Highly Efficient Amination

Chiba, Shunsuke; Narasaka, Koichi

doi:10.1002/9783527621262.ch1

Cited by 5 publications

(3 citation statements)

References 79 publications

(63 reference statements)

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“…Primary amines are among the most important and broadly utilized building blocks for the synthesis of drugs and pesticides (Figure ). More than 50% of the top-selling 200 pharmaceuticals by retail sales contain the amine moiety as the key pharmacophore . Many bioactive amines are known to be metabolized through oxidative deamination by monoamine oxidase enzymes .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of α-Deuterated Primary Amines via Reductive Deuteration of Oximes Using D₂O as a Deuterium Source

Lei

Lai

et al. 2021

J. Org. Chem.

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Selective introduction of the deuterium atom into the α-position of amines is important for the development of all types of novel deuterated drugs and agrochemicals due to the pervasive presence of amines. In this study, we report the first general single-electron-transfer reductive deuteration of both ketoximes and aldoximes using SmI2 as an electron donor and D2O as a deuterium source for the synthesis of α-deuterated primary amines with excellent levels of deuterium incorporations (>95% [D]). This protocol exhibits excellent chemoselectivity and tolerates a variety of functional groups. The potential application of this new method was showcased in the synthesis of deuterated drugs, such as rimantadine-d 4, the tebufenpyrad analogue, derivatives of nabumetone and pregnenolone, and a series of building blocks for the rapid and general assembly of deuterated drugs and pesticides.

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Section: Introductionmentioning

confidence: 99%

Synthesis of α-Deuterated Primary Amines via Reductive Deuteration of Oximes Using D₂O as a Deuterium Source

Lei

Lai

et al. 2021

J. Org. Chem.

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“…The formation of C–N bonds holds paramount significance in the synthesis of medicines, pharmaceutical molecules, and organic group functionalization. − In this context, the C–H functionalization approach offers a sustainable and atom-economical route for the synthesis of nitrogen-containing compounds. − Although direct functionalization of C–H bonds to create C–N bonds has been achieved, often, using expensive transition metal complexes, , C(sp 3 )–H functionalization presents a notable challenge due to the low polarity and poor reactivity of these bonds. − As a result, reports on the inter- and intramolecular functionalization of unactivated C–H bonds are relatively scarce …”

mentioning

confidence: 99%

Cu^I–Amidobis(phosphine)-Catalyzed Direct Amidation of Unactivated Alkanes via C(sp³)–H Activation

Sonawane,

Sabharwal,

Balakrishna

2024

Org. Lett.

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Herein, we describe an acid−base-free, sustainable, and efficient method for direct amidation of unactivated alkanes and toluene d e r i v a t i v e s , u s i n g t h e d i m e r i c C u I c o m p l e x [ C u I { o -Ph 2 PC 6 H 4 CONC 6 H 4 PPh 2 -o} 2 ] (here onward referred to as [PNP-Cu] 2 ). Using this method, C(sp 3 )−N bond formation was achieved through the activation of very challenging C(sp 3 )−H bonds in cycloalkanes, alkenes, allyl groups, and benzyl groups, with tolerance toward ketonic groups, heterocycles, and halide functionalities. One of the precatalysts, (PNHP-Cu-Npht) was isolated and structurally characterized. Isomerization in allyl-functionalized alkanes and selective benzylic alkylation in ketones were observed. This is a novel method for C(sp 3 )−N bond formation via direct N-alkylation of phthalimide, sulfonamide, benzamide, and phosphamidate.

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“…In the first approach (Fig. 1a), an electrophilic nitrogen source is reacted with an arylmetal and, after C–N bond formation, the activating group is removed, typically under harsh conditions (that is, strongly acidic hydrolysis at elevated temperatures) 28–31 . Additionally, the free primary amine has to be liberated from its salt using basic conditions.…”

mentioning

confidence: 99%

Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds

et al. 2016

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Arylmetals are highly valuable carbon nucleophiles that are readily and inexpensively prepared from aryl halides or arenes and widely used on both laboratory and industrial scales to react directly with a wide range of electrophiles. Although C–C bond formation has been a staple of organic synthesis, the direct transfer of primary amino (–NH2) and hydroxyl (–OH) groups to arylmetals in a scalable and environmentally friendly fashion remains a formidable synthetic challenge because of the absence of suitable heteroatom-transfer reagents. Here, we demonstrate the use of bench-stable N–H and N–alkyl oxaziridines derived from readily available terpenoid scaffolds as efficient multifunctional reagents for the direct primary amination and hydroxylation of structurally diverse aryl- and heteroarylmetals. This practical and scalable method provides one-step synthetic access to primary anilines and phenols at low temperature and avoids the use of transition-metal catalysts/ligands/additives, nitrogen-protecting groups, excess reagents and harsh workup conditions.

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Simple Molecules, Highly Efficient Amination

Cited by 5 publications

References 79 publications

Synthesis of α-Deuterated Primary Amines via Reductive Deuteration of Oximes Using D₂O as a Deuterium Source

Synthesis of α-Deuterated Primary Amines via Reductive Deuteration of Oximes Using D₂O as a Deuterium Source

Cu^I–Amidobis(phosphine)-Catalyzed Direct Amidation of Unactivated Alkanes via C(sp³)–H Activation

Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds

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Simple Molecules, Highly Efficient Amination

Cited by 5 publications

References 79 publications

Synthesis of α-Deuterated Primary Amines via Reductive Deuteration of Oximes Using D2O as a Deuterium Source

Synthesis of α-Deuterated Primary Amines via Reductive Deuteration of Oximes Using D2O as a Deuterium Source

CuI–Amidobis(phosphine)-Catalyzed Direct Amidation of Unactivated Alkanes via C(sp3)–H Activation

Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds

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Product

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Synthesis of α-Deuterated Primary Amines via Reductive Deuteration of Oximes Using D₂O as a Deuterium Source

Synthesis of α-Deuterated Primary Amines via Reductive Deuteration of Oximes Using D₂O as a Deuterium Source

Cu^I–Amidobis(phosphine)-Catalyzed Direct Amidation of Unactivated Alkanes via C(sp³)–H Activation