Tetramethylguanidinium azide (TMGA) - A versatile azidation agent

Abstract

(A) The nucleophilic ring opening of in situ formed D-glucal-derived allylic epoxides with TMGA proceeds in a 1,2-regio- and anti-stereoselective way.14b-c The noncoordinating nature of the counterion (TMG +) makes the epoxide react with the azide (N3-) in a noncoordinated fashion, necessarily at the C-3 oxirane carbon, affording the completely regio- and stereoselective result.14b (Chemical Equation Presented) (B) Propargyl azides containing 1- or 3-phenylthio functionalities were prepared by the reaction of the corresponding propargyl chlorides with TMGA. The selective oxidation of their sulfur atoms to sulfoxides and sulfones allows access to the propargyl azides bearing acceptor substituents. Sulfur-containing propargyl azides were successfully used for the synthesis of allenyl azides, 1,2,3-triazoles, bis(triazolo)pyrazine derivatives, and substituted vinyl azides.7 Acceptor-substituted propargyl azides were also converted into open-chain 1,2-diazidoethenes by one-pot reactions with TMGA.6b (Chemical Equation Presented) (C) α-Bromoacyl imidazolidinones react with TMGA to give, after auxiliary cleavage, α-amino acid derivatives in excellent yields and diastereoselectivities. 16c Similar methodologies (using oxazolidinones instead of imidazolidinones as chiral auxiliaries) were used for the asymmetric synthesis of many unusual α-amino acids.16a-b,d (Chemical Equation Presented) (D) TMGA is a versatile reagent for the stereoselective azidation of glycosyl derivatives.3,17 Per-O-acetylated D-glycopyranoses were first converted into glycosyl iodides, followed by the reaction with TMGA to give β-D-glycosyl azides stereoselectively after deacetylation. 17a β-Glycopyranosyl azides were next oxidized to glycopyranosyluronic acid azides. (Chemical Equation Presented) (E) Mitchinson and co-workers described the displacement of the bromine atom in the pyridazinone derivative using TMGA in DMF. The azide-substituted pyridazinone was next used for the preparation of 2,3,5-trisubstituted pyrazino[2,3-d] pyridazines, which are novel classes of GABAA receptor benzodiazepine binding-site ligands.18 (Chemical Equation Presented) (F) Gin and co-workers reported an elegant [4+2] annulation of vinyl carbodiimides with N-alkyl imines that resulted in a concise synthesis of batzelladine D, a marine guanidine alkaloid. The synthesis commenced with the addition of an azide derived from TMGA to 1,4-but-2-ynoic acid benzyl ester to give the β-azido acrylate in 84% yield (E/Z = 2:1).19 (Chemical Equation Presented) (G) Introduction of an azide group by a one-pot triflate activation of the free hydroxyl group, followed by azidation with TMGA, has been recently applied for the construction of phytosphingosine and α-galactosyl ceramide 20 as well as for the synthesis of glycaro-1,5-lactams and tetrahydrotetrazolopyridine-5-carboxylates.21 (Chemical Equation Presented). © Georg Thieme Verlag Stuttgart.