Intermolecular Ritter-Type C–H Amination of Unactivated sp<sup>3</sup> Carbons

Michaudel, Quentin; Thévenet, Damien; Baran, Phil S.

doi:10.1021/ja212020b

Cited by 249 publications

(150 citation statements)

References 58 publications

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“…The reaction was strictly stereoselective and formed the pure ketoamide with both the methyl and isopropylamide in equatorial positions. The properties of synthesized 2 agreed with the literature for 2 prepared via intermolecular Ritter-type C-H amination of menthone [3].Resonances in the PMR spectrum of 2 could not be fully assigned because of the mutual overlap of many of them. Nevertheless, the following conclusions could be drawn based on the spectrum.…”

supporting

confidence: 78%

Synthesis of Derivatives of the Monoterpenoid Pulegone

et al. 2015

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N-containing derivatives that were promising as biologically active compounds were synthesized via a series of transformations of the monoterpenoid pulegone isolated from Ziziphora clinopodioides essential oil.Pulegone (1) is a monocyclic unsaturated ketone of the p-menthane series and the principal component of Ziziphora clinopodioides Lam. [1] and Mentha longifolia L.[2] essential oils.Herein we present results for the synthesis of N-containing derivatives of 1 via a Ritter reaction with acetonitrile (MeCN) in the presence a catalytic amount of conc. H 2 SO 4 . Neutralization of the reaction mixture produced the ketoamide N-[2-(4-methyl-2-oxocyclohexyl)propan-2-yl]acetamide (2) in 56% yield and ~95% purity.Obviously, the process occurred through formation of a tertiary carbonium ion (3) with subsequent addition to it of MeCN and formation of the amide. The reaction was strictly stereoselective and formed the pure ketoamide with both the methyl and isopropylamide in equatorial positions. The properties of synthesized 2 agreed with the literature for 2 prepared via intermolecular Ritter-type C-H amination of menthone [3].Resonances in the PMR spectrum of 2 could not be fully assigned because of the mutual overlap of many of them. Nevertheless, the following conclusions could be drawn based on the spectrum.The C-4 methyl appeared as a doublet at 0.94 ppm. The resonance for the proton geminal to this methyl was a complicated multiplet that appeared at even stronger field (G 0.83 ppm), which indicated that it was axially oriented. Therefore, the ring did not invert during the reaction.The C-8 methyls gave singlets, which indicated unambiguously that MeCN added to this C atom (and not C-1 as an alternative). The resonances of these methyls were distinctly nonequivalent (G 1.17 and 1.33 ppm). This was consistent with hindered rotation around the C-1-C-8 bond that was obviously a consequence of the formation of a strong H-bond between the ketone and the acetamide (NH) H atom. The chemical shift of the acetamide methyl was 1.75 ppm.Conversely, the 13 C NMR spectrum of 2 was easily interpreted. Resonances were assigned by comparing them with those in spectra of previously synthesized analogs. Their multiplicities were determined using DEPT data. Thus, the spectrum showed two weak-field singlets characteristic of carbonyl C atoms at 210.2 and 168.3 ppm (the ketone and amide, respectively).

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confidence: 78%

Synthesis of Derivatives of the Monoterpenoid Pulegone

et al. 2015

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“…In addition to the issue of selectivity, there are more challenges toward the direct functionalization of sp 3 C-H bonds, including: their high bond dissociation energy, inaccessibility of the independent C-H bonding and antibonding orbitals as well as steric hindrance. In the past decades, great progress has been made in such fields to convert aliphatic sp 3 C-H bonds to C-C, C-O and C-B bonds in either stoichiometric or catalytic manner based on transition-metal catalysis [9][10][11][12][13][14][15] . The present article focuses on the direct amination of inert C sp3 -H bonds, especially primary C-H bonds to construct aza-heterocycles.…”

mentioning

confidence: 99%

Silver-catalysed direct amination of unactivated C–H bonds of functionalized molecules

et al. 2014

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Carbon-nitrogen bond formation from inert C-H bonds is an ideal organic transformation and a highly desirable method for the synthesis of N-containing molecules due to its high efficiency and atom economy. In this report, we develop a general reaction to achieve an unprecedented selective intramolecular amination of unactivated C-H bond in the absence of complex directing groups. Functionalized heterocyclic products are built up from readily available linear amines through simple and reliable silver catalysis, representing a new silver-based C-H functionalization. This method displays preference for primary sp 3 C-H bonds and exhibits distinct chemo-and regioselectivity compared to existing methods of direct amination (Hofmann-Löffler-Freytag reaction and nitrene insertion). The study highlights the manipulation of unfunctionalized groups in organic molecules to furnish complex structural units in the natural and bioactive molecules.

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“…heating and/or the presence of a strong oxidant such as N-fluoro-N′-(chloromethyl)-triethylenediamine pentafluoro phosphate (F-TEDA-PF 6 ) or ceric ammonium nitrate. [30][31][32][33] We found that 36b could be successfully aminated under mild conditions in CH 3 CN to afford 2,2,2-trifluoroethylether 39 in 49% yield using 35. These reactions may proceed via a carbocation intermediate generated by a two-electron oxidation process.…”

Section: Radical Catalystsmentioning

confidence: 92%

Enhanced Structural Variety of Nonplanar <i>N</i>-Oxyl Radical Catalysts and Their Application to the Aerobic Oxidation of Benzylic C–H Bonds

Kadoh

Oisaki

Kanai

2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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The design and synthesis of structurally variable, nonplanar N-oxyl radical catalysts and their application to the aerobic oxidation, etherification, and acetoamidation of benzylic C-H bonds are described. The catalytic oxidation of C-H bonds represents a powerful tool to synthesize oxygenated functional molecules from simple hydrocarbons in a straightforward way. Electron-deficient N-oxyl radical catalysts, such as phthalimidoyl N-oxyl (PINO) radical, generated from N-hydroxyphthalimide (1), have attracted much attention because of their applications in the oxidation of C-H bonds with high bond dissociation energy (BDE). However, a few sites in 1 are available for structural modifications and improvements of the catalytic performance. By replacing one carbonyl group in 1 with a trifluoromethyl (CF 3 )-substituted sp 3 -carbon, we generated an additional tunable site and a nonplanar backbone, while retaining the desirable electronwithdrawing properties and increasing the lipophilicity with respect to 1. We synthesized a variety of Nhydroxy pre catalysts containing such a CF 3 moiety, and investigated their utility in the aerobic oxidation of benzylic C-H bonds. Precatalysts with electron-withdrawing substituents, such as trifluoroethoxy and the acetophenone moieties, afforded higher yields than a corresponding methoxy-substituted analogue. The introduction of substituents at the aromatic ring was also effective, as evident from the performance of 7-CF 3 and 4,5,6,7-tetrafluoro precatalysts. Especially the combination of trifluoroethoxy-and 4,5,6,7-tetrafluoro substitution afforded a superior performance. These catalyst systems exhibited high functional group tolerance during the aerobic oxidation of C-H bonds, and benzylic etherification and Ritter-type reactions could be carried out at room temperature when a selected precatalyst and N-bromosuccinimide (NBS) were used.

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Intermolecular Ritter-Type C–H Amination of Unactivated sp³ Carbons

Cited by 249 publications

References 58 publications

Synthesis of Derivatives of the Monoterpenoid Pulegone

Synthesis of Derivatives of the Monoterpenoid Pulegone

Silver-catalysed direct amination of unactivated C–H bonds of functionalized molecules

Enhanced Structural Variety of Nonplanar <i>N</i>-Oxyl Radical Catalysts and Their Application to the Aerobic Oxidation of Benzylic C–H Bonds

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Intermolecular Ritter-Type C–H Amination of Unactivated sp3 Carbons

Cited by 249 publications

References 58 publications

Synthesis of Derivatives of the Monoterpenoid Pulegone

Synthesis of Derivatives of the Monoterpenoid Pulegone

Silver-catalysed direct amination of unactivated C–H bonds of functionalized molecules

Enhanced Structural Variety of Nonplanar <i>N</i>-Oxyl Radical Catalysts and Their Application to the Aerobic Oxidation of Benzylic C–H Bonds

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Intermolecular Ritter-Type C–H Amination of Unactivated sp³ Carbons