Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Feb 24;2017(8):1152-1176.
doi: 10.1002/ejoc.201601390. Epub 2016 Dec 22.

Metal-Catalysed Azidation of Organic Molecules

Monalisa Goswami  1 , Bas de Bruin  1
Affiliations
Review

Metal-Catalysed Azidation of Organic Molecules

Monalisa Goswami et al. European J Org Chem. .

Abstract

The azide moiety is a desirable functionality in organic molecules, useful in a variety of transformations such as olefin aziridination, C-H bond amination, isocyanate synthesis, the Staudinger reaction and the formation of azo compounds. To harness the versatility of the azide functionality fully it is important that these compounds be easy to prepare, in a clean and cost-effective manner. Conventional (non-catalysed) methods to synthesise azides generally require quite harsh reaction conditions that are often not tolerant of functional groups. In the last decade, several metal-catalysed azidations have been developed in attempts to circumvent this problem. These methods are generally faster, cleaner and more functional-group-tolerant than conventional methods to prepare azides, and can sometimes even be conveniently combined with one-pot follow-up transformations of the installed azide moiety. This review highlights metal-catalysed approaches to azide synthesis, with a focus on the substrate scopes and mechanisms, as well as on advantages and disadvantages of the methods. Overall, metal-catalysed azidation reactions provide shorter routes to a variety of potentially useful organic molecules containing the azide moiety.

Keywords: Azides; C–H activation; Noble‐metal catalysis; Radical reactions; Synthetic methods; Transition‐metal catalysis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Different reactions in which organic azides take part.
Scheme 1
Scheme 1
C–H azidation of anilines reported by Jiao and co‐workers.
Scheme 2
Scheme 2
Proposed mechanism of CuI‐catalysed azidation of anilines.
Scheme 3
Scheme 3
CuI‐catalysed o‐azidation of imines to produce benzimidazoles.
Scheme 4
Scheme 4
o‐Azidation of anilines with the aid of Cu(OAc)2 and further transformations.
Scheme 5
Scheme 5
CuI intramolecular imination followed by azidation.
Scheme 6
Scheme 6
CuCl2‐catalysed conversion of aryl ketones into benzamides.
Scheme 7
Scheme 7
Possible mechanism of the reaction depicted in Scheme 6.
Scheme 8
Scheme 8
Trifluoromethylation‐initiated azidation of carbonyl compounds.
Scheme 9
Scheme 9
Cu‐catalysed C–H azidation to give imidazoles.
Scheme 10
Scheme 10
Trifluoromethylation/azidation of alkynes with the aid of CuBr as reported by Liu and co‐workers.
Scheme 11
Scheme 11
Mechanistic aspects of the reaction depicted in Scheme 10.
Scheme 12
Scheme 12
CuI‐catalysed azidation and click reaction to afford phenanthridines.
Scheme 13
Scheme 13
Mechanism of the reaction depicted in Scheme 12.
Scheme 14
Scheme 14
Oxo‐azidation and alkoxy‐azidation of indoles catalysed by Cu(acac)2.
Scheme 15
Scheme 15
Azidation/cyclisation of tryptophols and tryptamines catalysed by Cu(OAc)2 ·H2O.
Scheme 16
Scheme 16
Co‐catalysed hydroazidation of alkenes.
Scheme 17
Scheme 17
C–H azidation aided by CuCl as reported by Suna and co‐workers.
Scheme 18
Scheme 18
Oxidative azidation/cyclisation of N‐arylenamines to give quinoxalines.
Scheme 19
Scheme 19
Azidocyanation of alkenes catalysed by Cu(TFA)2.
Scheme 20
Scheme 20
Azidotrifluoromethylation of styrenes catalysed by copper.
Scheme 21
Scheme 21
Top: light and dark reactions of styrene‐like alkenes in the presence of [Cu(dap)2]Cl. Bottom: benzylic C–H azidation catalysed by the same catalyst.
Scheme 22
Scheme 22
Enantioselective azidation of alkenes in the presence of a chiral ligand and a Cu catalyst.
Scheme 23
Scheme 23
Synthesis of azido‐substituted isoxazolines catalysed by copper.
Scheme 24
Scheme 24
Synthesis of azides from alkenes reported by Studer.
Scheme 25
Scheme 25
Mechanism of reaction depicted in Scheme 24.
Scheme 26
Scheme 26
Dearomative azidation of β‐naphthols.
Scheme 27
Scheme 27
Top: Cu‐catalysed synthesis of sulfonyl azides. Bottom: diazotisation when a C‐nucleophile is present.
Scheme 28
Scheme 28
Top: synthesis of imidazole‐1‐sulfonyl azide. bottom: Cu‐catalysed azide transfer to aliphatic azides by use of imidazole‐1‐sulfonyl azide.
Scheme 29
Scheme 29
FeCl3‐catalysed synthesis of glycosyl azides.
Scheme 30
Scheme 30
Conversion of tertiary silyl ethers into the corresponding azides.
Scheme 31
Scheme 31
Mechanism of iron‐catalysed azidation of silyl ethers.
Scheme 32
Scheme 32
Ring opening of THF to give hydroxy azides.
Scheme 33
Scheme 33
Synthesis of allylic azides reported by Ghorai and co‐workers.
Scheme 34
Scheme 34
FeII‐catalysed enantioselective azidation of β‐keto esters and oxindoles.
Scheme 35
Scheme 35
Stereoselective C–H azidation of decalin with the aid of FeIIL.
Scheme 36
Scheme 36
Selective C–H azidation of gibberlic acid performed with the aid of the FeII catalyst with chiral ligand.
Scheme 37
Scheme 37
Diastereoselective olefin diazidation of indene with the aid of a chiral FeII catalyst system.
Scheme 38
Scheme 38
Plausible mechanism of the reaction depicted in Scheme 37.
Scheme 39
Scheme 39
Mn(TMP)Cl‐catalysed azidation of cycloctane.
Scheme 40
Scheme 40
Proposed mechanism of (TMP)MnCl‐mediated azidation.
Scheme 41
Scheme 41
Oxidative azidation of cyclobutanols with the aid of Mn(OAc)3.
Scheme 42
Scheme 42
Phosphonation/azidation of alkenes in the presence of Mn(OAc)3.
Scheme 43
Scheme 43
Oxidative azidation of styrene to give the corresponding β‐azido alcohol.
Scheme 44
Scheme 44
Mechanism of the reaction depicted in Scheme 43.
Scheme 45
Scheme 45
Summary of the diastereodivergent cyclisation/azidation of 1,7‐enynes catalysed by Mn and Cu catalysts.
Scheme 46
Scheme 46
Pd(PPh3)4‐catalysed azidation of allyl acetates followed by reduction to corresponding amines by PPh3.
Scheme 47
Scheme 47
Pd‐catalysed azidation of a (Z)‐allyl acetate to give the (E) product.
Scheme 48
Scheme 48
Part of the total synthesis of (+)‐pancratistatin that employed Pd‐catalysed azidation.
Scheme 49
Scheme 49
C–H azidation of arylpyridines and subsequent N–N bond formation in the presence of PdII.
Scheme 50
Scheme 50
Mechanism of the reaction depicted in Scheme 49.
Scheme 51
Scheme 51
PdII‐catalysed allylic C–H azidation.
Scheme 52
Scheme 52
Ag‐catalysed synthesis of nitriles from alkynes by azidation.
Scheme 53
Scheme 53
Isolation of the vinyl azide intermediate and further reaction with TMSN3 and Ag2CO3 to give the nitrile product.
Scheme 54
Scheme 54
Proposed mechanism of the reaction depicted in Scheme 52.
Scheme 55
Scheme 55
Hydro‐azidation of ethynyl carbinols.
Scheme 56
Scheme 56
Synthesis of vinyl azides and azirines starting from the aldehyde in a gram‐scale reaction.
Scheme 57
Scheme 57
Proposed mechanism for the Ag‐catalysed hydroazidation of ethynyl carbinols.
Scheme 58
Scheme 58
Ag‐catalysed reaction of diynes to give fused triazoles.
Scheme 59
Scheme 59
Standardised reaction conditions for the reaction depicted in Scheme 57.
Scheme 60
Scheme 60
Experiment establishing the non‐involvement of Ag in the cyclisation step of the reaction depicted in Scheme 59.
Scheme 61
Scheme 61
Ag‐catalysed azidation of alkynes to give vinyl azides.
Scheme 62
Scheme 62
Ag‐catalysed azidation of allylic alcohols.
Scheme 63
Scheme 63
Ag‐catalysed decarboxylative azidation of carboxylic acids.
Scheme 64
Scheme 64
Top: formation of a cyclised side product confirming the involvement of a carbon radical. Bottom: proposed mechanism for decarboxylative azidation in the presence of Ag.
Scheme 65
Scheme 65
Gold‐catalysed azidation of allenes and further functionalisation.
Scheme 66
Scheme 66
Gold‐catalysed reaction of aryl–alkynes to give amides by azidation.
Scheme 67
Scheme 67
Mechanism of the reaction depicted in Scheme 66.
Scheme 68
Scheme 68
Au‐catalysed synthesis of tetrazoles from alkynes by use of the JohnPhos/Au system.
Scheme 69
Scheme 69
Proposed mechanism of the Au‐catalysed synthesis of tetrazoles from alkynes.
Scheme 70
Scheme 70
Rh‐catalysed azidation of arenes. DG = directing group.
Scheme 71
Scheme 71
Mechanism of the Rh‐catalysed azidation reactions of arenes depicted in Scheme 70.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Intrieri D., Zardi P., Caselli A. and Gallo E., Chem. Commun., 2014, 50, 11440–11453. - PubMed
    1. For a recent overview of metal‐catalysed click reactions, see: Wang C., Ikhlef D., Kahlal S., Saillard J.‐Y. and Astruc D., Coord. Chem. Rev., 2016, 316, 1–20.
    1. Bräse S., Gil C., Knepper K. and Zimmermann V., Angew. Chem. Int. Ed., 2005, 44, 5188–5240; - PubMed
    2. Angew. Chem., 2005, 117, 5320.
    1. Degennaro L., Trinchera P. and Luisi R., Chem. Rev., 2014, 114, 7881–7929. - PubMed
    1. a) van Kalkeren H. A., Bruins J. J., Rutjes F. P. J. T. and van Delft F. L., Adv. Synth. Catal., 2012, 354, 1417–1421;
    2. b) Takaoka A., Moret M. and Peters J. C., J. Am. Chem. Soc., 2012, 134, 6695–6706; - PubMed
    3. c) Bellow J. A., Yousif M., Cabelof A. C., Lord R. L. and Groysman S., Organometallics, 2015, 34, 2917–2923.

LinkOut - more resources