Chemical Synthesis

Hydroazidation Catalyst

New Hydroazidation Catalyst for Facile Preparation of Organoazides

The chemistry of organoazides is exceedingly rich, since the azide functionality reacts with electrophiles, nucleophiles, and dipolarophiles, with or without the extrusion of dinitrogen (Figure 1).  Common place transformation such as Staudinger reductions or ligations, Cu(I)-catalyzed Huisgen cycloadditions (of the “click” reaction family), Curtius or Schmidt rearrangents, nitrene reactions, or imine formation via aza-Wittig reactions all necessitate organoazide precursors or intermediates (Scheme 1).1


 


The most common route to alkyl azides uses a substitution reaction of primary or secondary alkyl halides with inorganic azides, or via hydroazidation of alkenes.  The latter case, however, is limited to those olefins which give stabilized carbocations and requires the use of somewhat dangerous hydrazoic acid, HN3 or the safer alternative, TMSN3.  Carreira and co-workers recently reported the   Co(II)-catalyzed hydroazidation of unactivated olefins with p-toluenesulfonyl azide (TsN3) to yield alkyl azides (Scheme 2).2 The catalyst is easily prepared in situ from Co(BF4)2 · 6H2O and a Schiff base ligand.  Mono-, di-, and trisubstituted olefins are tolerated in the hydroazidation reaction and complete Markovnikov selectivity is observed.  The hydroazidation reaction exhibits good functional group tolerance, with ester and silyl ether groups surviving the reaction conditions without issue.  Additionally, the in situ-generated alkyl azides can be directly converted to amines (via reduction) or triazoles (via   Cu(I)-catalyzed cycloaddition) in a one-pot process.


Sigma-Aldrich is pleased to offer the precursors to this useful catalyst, in addition to a variety of other reagents for azide formation.


Product Information

Prod. No. Product Name/Description Structure Add to Cart
676551 Potassium 2-(3,5-di-tert-butyl-2-hydroxybenzylideneamino)-2,2-diphenylacetate, 95%
399957 Cobalt(II) tetrafluoroborate hexahydrate, 99%> Co(BF4)2 · 6H2O
S8032 Sodium Azide NaN3
404764 4-Acetamidobenzenesulfonyl azide
340138 4-Carboxybenzenesulfonazide, 97%
155071 Azidotrimethylsilane, 95%
178756 Diphenyl phosphoryl azide, 97%

  • Click Chemistry: A "Click" Away From Discovery (Click here to view.)

References:

  1. For an excellent review of the diverse chemistry of organoazides, see:  Bräse, S. et al. Angew. Chem., Int. Ed. 2005, 44, 5188.
  2. (a) Waser, J. et al. J. Am. Chem. Soc. 2006, 128, 11693.
    (b) Waser, J. et al. J. Am. Chem. Soc. 2005, 127, 8294.
    (c) p-Toluenesulfonyl azide, TsN3, can be readily prepared from TsCl and sodium azide: Organic Syntheses 1973, Coll. Vol. 5, 179.