In situ generation of N-unsubstituted imines from alkyl azides and their applications for imine transfer via copper catalysis

Hu, Lu; Liu, Yahu A.; Liao, Xuebin

doi:10.1126/sciadv.1700826

Cited by 13 publications

(6 citation statements)

References 89 publications

(98 reference statements)

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“…Other strategies to avoid decomposition of N -unsubstituted aldimines include independent routes to their synthesis and subsequent trapping. These approaches involve protecting the vulnerable N atom with Lewis acids and then deprotecting, hydrogenating nitriles in the presence of a suitable trap, , and, more recently, deazotation and rearranging benzylic azides in the presence of a suitable nucleophile. − , The latter two transformations utilize various transition metal complexes, some of which can even perform this reaction catalytically. ,,, Specifically, Park and co-workers have used benzylic azides to synthesize chiral amines via the formation of N -unsubstituted imines with a [Cp ∧ Ru(CO) 2 ] 2 (Cp ∧ = N -isopropyl amino, 2,5-dimethyl, 3,4-diphenyl cyclopentadienyl) catalyst under photolytic conditions . They later extended this methodology to the catalytic synthesis of 1 H -azadienes from allyl azides …”

Section: Introductionsupporting

confidence: 89%

“…N -Unsubstituted aldimines are an important class of molecules implicated as intermediates in the synthesis of pharmaceutically relevant compounds, such as diamines, , chiral amines, − amides, 1 H -azadienes, and substituted pyridines and indoles . Because of the unsubstituted nature of these aldimines at both nitrogen and carbon, these species are too reactive to be isolated using conventional routes, such as the condensation of the corresponding aldehyde with ammonia. , As a result, the latter approach must be conducted in situ in order to generate and trap this elusive molecule.…”

Section: Introductionmentioning

confidence: 99%

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Iron(II) Mediated Deazotation of Benzyl Azide: Trapping and Subsequent Transformations of the Benzaldimine Fragment

et al. 2022

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The mono-benzaldimine (HNCHPh) complex [( tBupyrpyrr2)Fe(HNCHPh)] (1-HNCHPh) has been prepared by reaction of [( tBupyrpyrr2)Fe(OEt2)] (1-OEt2) ( tBupyrpyrr2 = 2,6-bis(3,5-di-tert-butyl-pyrrolyl)pyridine) with one equivalent of benzyl azide. Compound 1-HNCHPh retains the cis-divacant octahedral coordination geometry akin to 1, as established by single crystal X-ray diffraction study. A bis-HNCHPh complex [( tBupyrpyrr2)Fe(HNCHPh)2] (2) was also prepared by the addition of two equivalents of benzyl azide to 1, and its molecular structure exhibits the two HNCHPh ligands coordinated trans to each other, thereby forming a square pyramidal coordination geometry at the FeII center. Reaction of 1 with excess benzyl azide yields [( tBupyrpyrr2)Fe(HNCHPh)2·PhCHNCH(NH2)Ph] (2-PhCHNCH(NH2)Ph), which contains an unstable benzylideneamino phenyl methanamine fragment, effectively hydrogen bonded to 2. Thermolysis of 2 or 2-PhCHNCH(NH2)Ph releases the HNCHPh self-coupling products hydrobenzamide (A), N-benzylidine benzylamine (B), and benzonitrile (C). Under catalytic conditions, free HNCHPh (cis/trans-HNCHPh mixture) is produced using 2.5 mol % of 1 in 90% spectroscopic yield. These studies provide a clearer understanding for the conversion of the HNCHPh in 2 or 2-PhCHNCH(NH2)Ph to the C–C and C–N coupled products. Reduction of 1-HNCHPh with KC8 yields the reductively coupled benzylamide complex [K(OEt2)]2[( tBupyrpyrr2)2Fe2(μ2-NHCHPhCHPhNH)] (3) as the result of a new C–C bond formed between two radical benzylamide fragments.

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Section: Introductionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Iron(II) Mediated Deazotation of Benzyl Azide: Trapping and Subsequent Transformations of the Benzaldimine Fragment

et al. 2022

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“…Substituted pyridines and indoles were synthesized through trapping of N–H imines, generated in situ via copper-catalyzed transformation of alkyl azides (Scheme ). Various symmetrical and unsymmetrical 3,5-diarylpyridines were obtained using CuBr 2 as a catalyst, sterically hindering phenanthroline-based ligands, and AgSbF 6 as an additive in HFIP solvent (Scheme a). Toluene and THF resulted in poor reaction outcomes, whereas no reaction was observed with dioxane.…”

Section: Cyclization Reactionsmentioning

confidence: 99%

HFIP in Organic Synthesis

et al. 2022

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1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) is a polar, strongly hydrogen bond-donating solvent that has found numerous uses in organic synthesis due to its ability to stabilize ionic species, transfer protons, and engage in a range of other intermolecular interactions. The use of this solvent has exponentially increased in the past decade and has become a solvent of choice in some areas, such as C–H functionalization chemistry. In this review, following a brief history of HFIP in organic synthesis and an overview of its physical properties, literature examples of organic reactions using HFIP as a solvent or an additive are presented, emphasizing the effect of solvent of each reaction.

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“…hydride shift, leading to the formation of the undesired imine. 10 A gram scale reaction of 1a under the standard reaction conditions afforded 3aa in 90% yield, which was easily converted to the ester 4 and amide 5 in a simple operation under mild reaction conditions (Scheme 2). 6 The amidation reaction can also be performed in a two-neck round-bottom flask under reflux conditions, giving 3aa in a comparable yield.…”

mentioning

confidence: 99%

“…The 2-propyldioxazolone 2n was slightly less reactive and required a higher catalyst loading and elevated temperature. This can be attributed to the metal nitrene intermediate competing with an unproductive 1,2-hydride shift, leading to the formation of the undesired imine …”

mentioning

confidence: 99%

Iridium(III)-Catalyzed Direct Intermolecular Chemoselective α-Amidation of Masked Aliphatic Carboxylic Acids with Dioxazolones via Nitrene Transfer

et al. 2021

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The Ir(III)-catalyzed direct α-C−H amidation of imidazole-masked aliphatic carboxylic acids with dioxazolones is reported. The presence of an imidazole moiety as a directing group is a key to the success of the reaction. The products can be easily converted to esters and amides in a simple procedure. The reaction shows a broad substrate scope for various substituted 2acylimidazoles, as well as a variety of dioxazolone derivatives with important functional groups being tolerated. The reaction mechanism was investigated by deuterium-labeling experiments, Hammett plots, NMR, and FAB-MS, and we propose the generation of an iridium nitrene intermediate.

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In situ generation of N-unsubstituted imines from alkyl azides and their applications for imine transfer via copper catalysis

Abstract: Multisubstituted pyridines or indoles were synthesized using N-unsubstituted imines in situ–generated from alkyl azides.

Cited by 13 publications

References 89 publications

Iron(II) Mediated Deazotation of Benzyl Azide: Trapping and Subsequent Transformations of the Benzaldimine Fragment

Iron(II) Mediated Deazotation of Benzyl Azide: Trapping and Subsequent Transformations of the Benzaldimine Fragment

HFIP in Organic Synthesis

Iridium(III)-Catalyzed Direct Intermolecular Chemoselective α-Amidation of Masked Aliphatic Carboxylic Acids with Dioxazolones via Nitrene Transfer

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