Metal‐ and Base‐Free Room‐Temperature Amination of Organoboronic Acids with <i>N</i>‐Alkyl Hydroxylamines

Sun, Hongbao; Gong, Liang; Tian, Yu-Biao; Wu, Jin‐Gui; Zhang, Xia; Liu, Jie; Fu, Zhen‐Guo; Niu, Dawen

doi:10.1002/anie.201802782

Cited by 42 publications

(18 citation statements)

References 86 publications

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“…We surmise that the apparent solvent influence in the competition experiments (section ) operates by stabilization of partial charge build-up in the transition states leading to and from dipolar structure Int-4 (i.e., TS-4 and TS-5 ), relative to dissociative loss of phosphetane oxide 1 ·[O]. In analogy to numerous related electrophilic amination reactions of organoboron reagents, ,,− an ensuing 1,2-metalate rearrangement of betaine Int-4 results in the formation of the desired C–N bond, which either upon hydrolysis with adventitious water or upon workup gives the target amine. A final hydrosilane-mediated reduction of phosphetane oxide 1 ·[O] returns the catalyst to the P(III) resting state ( 1 ) and closes the second catalytic deoxygenation cycle.…”

Section: Discussionmentioning

confidence: 99%

An Improved P^III/P^V═O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps

Nykaza

Cooper

et al. 2020

J. Am. Chem. Soc.

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Experimental, spectroscopic, and computational studies are reported that provide an evidence-based mechanistic description of an intermolecular reductive C−N coupling of nitroarenes and arylboronic acids catalyzed by a redox-active maingroup catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide, i.e., 1• [O]). The central observations include the following: (1) catalytic reduction of 1•[O] to P III phosphetane 1 is kinetically fast under conditions of catalysis; (2) phosphetane 1 represents the catalytic resting state as observed by 31 P NMR spectroscopy; (3) there are no long-lived nitroarene partial-reduction intermediates observable by 15 N NMR spectroscopy; (4) the reaction is sensitive to solvent dielectric, performing best in moderately polar solvents (viz. cyclopentylmethyl ether); and (5) the reaction is largely insensitive with respect to common hydrosilane reductants. On the basis of the foregoing studies, new modified catalytic conditions are described that expand the reaction scope and provide for mild temperatures (T ≥ 60 °C), low catalyst loadings (≥2 mol%), and innocuous terminal reductants (polymethylhydrosiloxane). DFT calculations define a two-stage deoxygenation sequence for the reductive C−N coupling. The initial deoxygenation involves a ratedetermining step that consists of a (3+1) cheletropic addition between the nitroarene substrate and phosphetane 1; energy decomposition techniques highlight the biphilic character of the phosphetane in this step. Although kinetically invisible, the second deoxygenation stage is implicated as the critical C−N product-forming event, in which a postulated oxazaphosphirane intermediate is diverted from arylnitrene dissociation toward heterolytic ring opening with the arylboronic acid; the resulting dipolar intermediate evolves by antiperiplanar 1,2-migration of the organoboron residue to nitrogen, resulting in displacement of 1•[O] and formation of the target C−N coupling product upon in situ hydrolysis. The method thus described constitutes a mechanistically well-defined and operationally robust main-group complement to the current workhorse transition-metal-based methods for catalytic intermolecular C−N coupling.

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Section: Discussionmentioning

confidence: 99%

An Improved P^III/P^V═O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps

Nykaza

Cooper

et al. 2020

J. Am. Chem. Soc.

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“…The reaction was then tested with another nucleophile, hydroxylamine, also known to afford multiple products with halides . Typically N -alkylhydroxylamines are prepared by reduction of oximes under mild conditions or by reduction of a nitro group. , The reaction of commercially available 50% hydroxylamine solution with phenethyl bromide in continuous flow afforded the corresponding N -alkylhydroxylammonium salt. To separate the desired product from the remaining hydroxylamine, the resulting salt was treated with a saturated aqueous solution of sodium bicarbonate, affording the corresponding N -alkylhydroxylamine (Table ).…”

mentioning

confidence: 99%

Chemoselective Synthesis of Amines from Ammonium Hydroxide and Hydroxylamine in Continuous Flow

et al. 2018

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The chemoselective amination of alkyl bromides and chlorides with aqueous ammonia and hydroxylamine was achieved in continuous flow to produce primary ammonium salts and hydroxylamines in high yields. An in-line workup was designed to isolate the corresponding primary amine, which was also telescoped in further reactions, such as acylation and Paal–Knorr pyrrole synthesis. Monosubstituted epoxides are also compatible with the reaction conditions.

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“…Thus, several works relied on the use of hydroxylamine derivatives or analogs, for example, methoxyamine/nBuLi [123] or tBuOK [124] (Scheme 34 A), MeONH 2 •HCl [125] or NH 2 CN [126] /(bis (trifluoroacetoxy)iodo)benzene (PIFA)/NBS (B), and N-alkylhydroxylamines in the presence of Cl 3 CCN (C). [127] Another approach to the synthesis of secondary amines 129 was proposed by Aggarwal and co-workers; they applied alkyl azides as the amination reagents in both inter-and intramolecular fashion (Scheme 34 D; see also Scheme 31). [128] It should be noted that the latter method is an adaptation of an earlier protocol by Matteson and Kim involving generation of alkyldihaloborane intermediates.…”

Section: Barluenga-valdés Cross-couplingmentioning

confidence: 99%

Saturated Boronic Acids, Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry

Volochnyuk

Gorlova

Grygorenko

2021

Chemistry A European J

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This review discusses recent advances in the chemistry of saturated boronic acids, boronates, and trifluoroborates. Applications of the title compounds in the design of boron-containing drugs are surveyed, with special emphasis on α-amino boronic derivatives. A general overview of saturated boronic compounds as modern tools to construct C(sp 3 )À C and C(sp 3 )-heteroatom bonds is given, including recent developments in the Suzuki-Miyaura and Chan-Lam cross-couplings, single-electron-transfer processes including metallo-and organocatalytic photoredox reactions, and transformations of boron "ate" complexes. Finally, an attempt to summarize the current state of the art in the synthesis of saturated boronic acids, boronates, and trifluoroborates is made, with a brief mention of the "classical" methods (transmetallation of organolithium/magnesium reagents with boron species, anti-Markovnikov hydroboration of alkenes, and the modification of alkenyl boron compounds) and a special focus on recent methodologies (boronation of alkyl (pseudo)halides, derivatives of carboxylic acids, alcohols, and primary amines, boronative CÀ H activation, novel approaches to alkene hydroboration, and 1,2-metallate-type rearrangements).

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Metal‐ and Base‐Free Room‐Temperature Amination of Organoboronic Acids with N‐Alkyl Hydroxylamines

Cited by 42 publications

References 86 publications

An Improved P^III/P^V═O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps

An Improved P^III/P^V═O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps

Chemoselective Synthesis of Amines from Ammonium Hydroxide and Hydroxylamine in Continuous Flow

Saturated Boronic Acids, Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry

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Metal‐ and Base‐Free Room‐Temperature Amination of Organoboronic Acids with N‐Alkyl Hydroxylamines

Cited by 42 publications

References 86 publications

An Improved PIII/PV═O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps

An Improved PIII/PV═O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps

Chemoselective Synthesis of Amines from Ammonium Hydroxide and Hydroxylamine in Continuous Flow

Saturated Boronic Acids, Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry

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An Improved P^III/P^V═O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps

An Improved P^III/P^V═O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps