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. 2019 May 22;141(20):8104-8109.
doi: 10.1021/jacs.9b04189. Epub 2019 May 8.

Transition-Metal- and Light-Free Directed Amination of Remote Unactivated C(sp3)-H Bonds of Alcohols

Daria Kurandina  1 , Dongari Yadagiri  1 , Mónica Rivas  1 , Aleksei Kavun  1 , Padon Chuentragool  1 , Keiichi Hayama  1 , Vladimir Gevorgyan  1
Affiliations

Transition-Metal- and Light-Free Directed Amination of Remote Unactivated C(sp3)-H Bonds of Alcohols

Daria Kurandina et al. J Am Chem Soc. .

Abstract

Due to the great value of amino alcohols, new methods for their synthesis are in high demand. Abundant aliphatic alcohols represent the ideal feedstock for the method development toward this important motif. To date, transition-metal-catalyzed approaches for the directed remote amination of alcohols have been well established. Yet, they have certain disadvantages such as the use of expensive catalysts and limited scope. Very recently, transition-metal-free visible-light-induced radical approaches have emerged as new powerful tools for directed remote amination of alcohols. Relying on 1,5-HAT reactivity, these methods are limited to β - or δ-amination only. Herein, we report a novel transition-metal- and visible-light-free room-temperature radical approach for remote β -, γ-, and δ-C(sp3)-N bond formation in aliphatic alcohols using mild basic conditions and readily available diazonium salt reagents.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1.
Scheme 1.
Directed Remote C–H Amination of Alcohols
Scheme 2.
Scheme 2.. Scope of Transition-Metal-Free Amination of Remote Unactivated C(sp3)–H Sites of Aliphatic Alcohols:a (a) γ-Diazenylation; (b) β-Diazenylation; (c) δ-Diazenylation; (d) Diazenylation at Secondary and Primary C–H Sites
a0.3 or 0.4 mmol scale reactions. Isolated yield,%. bNMR yield,% (standard: CH2Br2). cWhen R5 = OH (3p): 20% NMR yield; R5 = NH2 (3q): decomp; R5 = Br (3r): decomp. dProducts 3 were deprotected and isolated as free alcohols 4. eCalculated yield, %. fMixture of regio- or stereoisomers: NMR yield of major isomer is represented.
Scheme 3.
Scheme 3.. Transformations of Diazenylated Alcohols: Hydrogenation toward Amino Alcoholsa
a0.3–0.4 mmol scale reactions. Isolated yield, %.
Scheme 4.
Scheme 4.. Transformations of Diazenylated Alcohols: Oxygenation toward Hydroxy Ketonesa
a0.2–0.4 mmol scale reactions. Isolated yield, %. bCompound synthesized via a semi-one-pot procedure from the corresponding Si-auxiliary protected alcohol 1ay. Isolated yield over two steps, %.
See this image and copyright information in PMC

References

    1. Ager DJ; Prakash I; Schaad DR 1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in Asymmetric Synthesis. Chem. Rev 1996, 96, 835. - PubMed
    2. Bergmeier SC The Synthesis of Vicinal Amino Alcohols. Tetrahedron 2000, 56, 2561.
    3. Lait SM; Rankic DA; Keay BA 1,3-Aminoalcohols and Their Derivatives in Asymmetric Organic Synthesis. Chem. Rev 2007, 107, 767. - PubMed
    4. Gomes CRB; Moreth M; Cardinot D; Kopke V; Cunico W; Da Silva Lourenio MC; De Souza MVN Synthesis and Antimycobacterial Activity of Novel Amino Alcohols Containing Central Core of the Anti-HIV Drugs Lopinavir and Ritonavir. Chem. Biol. Drug Des 2011, 78, 1031. - PubMed
    5. Quiliano M; Mendoza A; Fong KY; Pabón A; Goldfarb NE; Fabing I; Vettorazzi A; López de Cerain A; Dunn BM; Garavito G; Wright DW; Deharo E; Pérez-Silanes S; Aldana I; Galiano S Exploring the scope of new arylamino alcohol derivatives: Synthesis, antimalarial evaluation, toxicological studies, and target exploration. Int. J. Parasitol.: Drugs Drug Resist 2016, 6, 184. - PMC - PubMed
    1. Davies HML; Manning JR Catalytic C-H functionalization by metal carbenoid and nitrenoid insertion. Nature 2008, 451, 417. - PMC - PubMed
    2. Du Bois J Rhodium-Catalyzed C-H Amination. An Enabling Method for Chemical Synthesis. Org. Process Res. Dev 2011, 15, 758. - PMC - PubMed
    3. Roizen JL; Harvey ME; Du Bois J Metal-Catalyzed Nitrogen-Atom Transfer Methods for the Oxidation of Aliphatic C-H Bonds. Acc. Chem. Res 2012, 45, 911. - PMC - PubMed
    4. Jeffrey JL; Sarpong R Intramolecular C(sp3)-H amination. Chem. Sci 2013, 4, 4092.
    5. Darses B; Rodrigues R; Neuville L; Mazurais M; Dauban P Transition metal-catalyzed iodine(III)-mediated nitrene transfer reactions: efficient tools for challenging syntheses. Chem. Commun 2017, 53, 493. - PubMed
    6. Park Y; Kim Y; Chang S Transition Metal-Catalyzed C-H Amination: Scope, Mechanism, and Applications. Chem. Rev 2017, 117, 9247. - PubMed
    1. Espino CG; Wehn PM; Chow J; Du Bois J Synthesis of 1,3-Difunctionalized Amine Derivatives through Selective C-H Bond Oxidation. J. Am. Chem. Soc 2001, 123, 6935.
    2. Espino CG; Fiori KW; Kim M; Du Bois J Expanding the Scope of C-H Amination through Catalyst Design. J. Am. Chem. Soc 2004, 126, 15378. - PubMed
    3. Espino CG; Du Bois J A Rh-Catalyzed C-H Insertion Reaction for the Oxidative Conversion of Carbamates to Oxazolidinones. Angew. Chem., Int. Ed 2001, 40, 598. - PubMed
    4. Grelier G; Rey-Rodriguez R; Darses B; Retailleau P; Dauban P Catalytic Intramolecular C(sp3)-H Amination of Carbamimidates. Eur. J. Org. Chem 2017, 82, 1880. - PubMed
    5. Lebel H; Mamani Laparra L; Khalifa M; Trudel C; Audubert C; Szponarski M; Dicaire Leduc C; Azek E; Ernzerhof M Synthesis of Oxazolidinones: Rhodium-catalyzed C-H Amination of N-Mesyloxycarbamates. Org. Biomol. Chem 2017, 15, 4144. - PubMed
    1. Milczek E; Boudet N; Blakey S Enantioselective C-H Amination Using Cationic Ruthenium(II)-pybox Catalysts. Angew. Chem., Int. Ed 2008, 47, 6825. - PubMed
    2. Liang J-L; Yuan S-X; Huang J-S; Yu W-Y; Che C-M Highly Diastereo- and Enantioselective Intramolecular Amidation of Saturated C-H Bonds Catalyzed by Ruthenium Porphyrins. Angew. Chem., Int. Ed 2002, 41, 3465. - PubMed
    3. Zhang J-L; Huang J-S; Che C-M Oxidation Chemistry of Poly(ethylene glycol)-Supported Carbonylruthenium(II) and Dioxoruthenium(VI) meso-Tetrakis(pentafluorophenyl)porphyrin. Chem. - Eur. J 2006, 12, 3020. - PubMed
    1. Alderson JM; Phelps AM; Scamp RJ; Dolan NS; Schomaker JM Ligand-Controlled, Tunable Silver-Catalyzed C-H Amination. J. Am. Chem. Soc 2014, 136, 16720. - PMC - PubMed

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