Iron-catalyzed carboazidation of alkenes and alkynes

Carboazidation of alkenes and alkynes holds the promise to construct valuable molecules directly from chemical feedstock therefore is significantly important. Although a few examples have been developed, there are still some unsolved problems and lack of universal methods for carboazidation of both alkenes and alkynes. Here we describe an iron-catalyzed rapid carboazidation of alkenes and alkynes, enabled by the oxidative radical relay precursor t-butyl perbenzoate. This strategy enjoys success with a broad scope of alkenes under mild conditions, and it can also work with aryl alkynes which are challenging substrates for carboazidation. A large number of diverse structures, including many kinds of amino acid precursors, fluoroalkylated vinyl azides, other specific organoazides, and 2H-azirines can be easily produced.


Supplementary information
All reactions were carried out under an atmosphere of nitrogen in dried glassware with magnetic stirring unless otherwise indicated. Unless otherwise noted, materials obtained from commercial suppliers were used without further purification. Solvents were dried by Innovative Technology Solvent Purification System. Liquids and solutions were transferred via syringe. All reactions were monitored by thin-layer chromatography. GC and GC-MS data were recorded on Thermo Trace 1300 and Thermo ISQ QD, respectively. 1 H, 19 F and 13 C NMR spectra were recorded on Bruker-BioSpin AVANCE III HD-400 Hz. Data for 1 H NMR spectra are reported relative to chloroform as an internal standard (7.26 ppm) and are reported as follows: chemical shift (ppm), multiplicity, coupling constant (Hz), and integration. Data for 13 C NMR spectra were reported relative to chloroform as an internal standard (77.00 ppm) and are reported in terms of chemical shift (ppm). IR data were obtained from Bruker VERTEX 70. All melting points were determined on a Beijing Science Instrument Dianguang Instrument Factory XT4B melting point apparatus and are uncorrected. HRMS(ESI) data were recorded on Bruker Impact II UHR-TOF; HRMS(EI) data were recorded on Waters Micromass GCT Premier.

Optimization of the reaction conditions Optimization for carboazidation of alkenes
To a dried Schlenk tube equipped with a magnetic bar, catalyst (x mmol) was added, then this tube was flushed with nitrogen gas (3 times) and maintained a nitrogen atmosphere using a nitrogen balloon. A thoroughly mixed solution of vinylarene 1a (0.5 mmol), alkyl iodide 2a

Optimization for carboazidation of alkynes
To a dried Schlenk tube equipped with a magnetic bar, catalyst (0.025 mmol) was added, then this tube was flushed with nitrogen gas (3 times) and maintained a nitrogen atmosphere using a nitrogen balloon. A thoroughly mixed solution of 80 (0.5 mmol), RfI (0.7 mmol), TMSN3 (1.0 mmol) and TBPB (1.0 mmol) in solvent (2 mL) was added to the catalyst via syringe and stirred vigorously for 4 h at room temperature. The yield of the product 81 and 81' was determined by 1 H NMR analysis using CH2Br2 as an internal standard. Supplementary

General procedure for carboazidation of alkenes and alkynes General procedure A: Carboazidation of alkenes
To a dried Schlenk tube equipped with a magnetic bar, Fe(OTf)2 (9 mg, 0.025 mmol) was added, Then this tube was flushed with nitrogen gas (3 times) and maintained a nitrogen atmosphere using a nitrogen balloon. A thoroughly mixed solution of alkene (0.5 mmol), alkyl iodide (0.65-1.5 mmol), TMSN3 (0.7-1.7 mmol) and TBPB (0.75-1.75 mmol) in DME (2 mL) was added to the catalyst via syringe and the mixture was stirred vigorously for 3 -120 minutes at appropriate temperature. After completion (TLC), the solvent was evaporated and the residue was purified by flash chromatography on silica gel using petroleum ether and ethyl acetate to give the corresponding product.

General procedure B: Carboazidation of alkynes for the synthesis of 2H-azirines
To a dried Schlenk tube equipped with a magnetic bar, Fe(OTf)3 (12.7 mg, 0.025 mmol) was added, Then this tube was flushed with nitrogen gas (3 times) and maintained a nitrogen atmosphere using a nitrogen balloon. A thoroughly mixed solution of alkyne (0.5 mmol), RfI (0.75 mmol), TMSN3 (1.0 mmol) and TBPB (1.0 mmol) in DME (2 mL) was added to the catalyst via syringe and the mixture was stirred vigorously for 5 -20 minutes at room temperature. After completion (TLC), the volatile compounds were removed by pump and the residue was dissolved in 3 mL of toluene. The resulting mixture was then stirred at 120 o C for 10 minutes. The solvent was evaporated and the residue was purified by flash chromatography on silica gel using petroleum ether and ethyl acetate to give the corresponding product.

(b) Synthesis of 1,2,3-triazole 109
To a solution of vinyl azide (0.5 mmol) and phenylacetylene (1.0 mmol) in toluene (2 mL) was added CuTc (0.15 mmol), and the reaction mixture was stirred at 25 o C for 8 h. After completion (TLC), the solvent was evaporated and the residue was purified by flash chromatography on silica gel using petroleum ether and ethyl acetate to give the corresponding product 109 (yield: 207 mg, 81%

(c) Transformation of 2H-azirine
A mixture of 3-iodoprop-1-ene (1.5 mmol) and indium powder (1.0 mmol) in THF (2 mL) was stirred at room temperature for 1 h. To the resulting solution, 82 (0.50 mmol) was added and the mixture was stirred at room temperature for another 3 h. The reaction was quenched with water (10 mL) and the product was extracted with ether. The extracts were washed successively with water, brine, and dried over Na2SO4. The solvent was evaporated and the residue was purified by flash chromatography on silica gel using petroleum ether and ethyl acetate to give the corresponding product 110 (yield: 196 mg, 93%

Single crystal data of compound 109
Crystal data and structure refinements of 109 is listed in Supplementary Table 3. CCDC number is 1864994. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.