Selective transition-metal-free vicinal cis-dihydroxylation of saturated hydrocarbons† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc03055f Click here for additional data file.

A selective vicinal dihydroxylation of alkanes by dual C(sp3)–H bond functionalization under transition-metal-free reaction conditions has been developed.


General
All reactions were carried out under ambient atmosphere at room temperature. Unless otherwise noted, all commercially available compounds were used as provided without any further purification. Solvents for chromatography were laboratory grade. Analytical thin-layer chromatography (TLC) was performed on Merck silica gel aluminum plates with F-254 indicator, visualized by irradiation with UV light. Column chromatography was performed using silica gel Merck 60 (particle size 0.040-0.063 mm). All functionalized alkanes were visualized using p-anisaldehyde staining solution (5 mL glacial sulfuric acid, 1.5 mL glacial acetic acid and 3.7 mL p-anisaldehyde in 135 mL absolute EtOH). 1 H-NMR and 13 C-NMR were recorded on a Bruker DRX400 (400 MHz), Bruker DRX500 (500 MHz) and Bruker DRX600 (600 MHz) spectrometer in CDCl 3 as solvent. Spectra were calibrated relative to solvent's residual proton and carbon chemical shift: CDCl 3 (δ = 7.26 ppm for 1 H-NMR and δ = 77.16 ppm for 13 C NMR). Diastereomers are defined in the following manner: # denotes major-and * minor diastereomer signals. Data are reported in the following order: chemical shift (d) in ppm; multiplicities are indicated br. s. (broadened singlet), s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet); coupling constants (J) are given in Hertz (Hz). Low resolution mass spectra (MS-EI, 70 eV) were collected using a GC-MS (GC system 7890A equipped with 5975C detector) produced by Agilent Technologies (column: HP-5MS, 30 m × 0.250 mm × 0.25 μm). High resolution mass spectra were recorded on a LTQ Orbitrap mass spectrometer coupled to an Accela HPLC System (HPLC column: Hypersyl GOLD, 50 mm × 1 mm, 1.9 μm). Fourier transform infrared spectroscopy (FT-IR) spectra were obtained with a Bruker Tensor 27 spectrometer (ATR, neat) and are reported in terms of frequency of absorption (cm -1 ). Reported yields of products correspond to isolated compounds after column chromatography.

Safety-concerns:
We have not experienced any explosions while conducting our experiments; however, much care should be taken when working with azides as they are potentially explosive compounds. The reaction proceeds exothermically upon addition of azides. Therefore, water bath cooling has to be applied to the reaction, when performing scales above 0.3 mmol.     hours at room temperature. After completion, the reaction was diluted with dichloromethane, neutralized with 1 M NaOH solution (25 mL) and washed with saturated Na 2 SO 3 solution (10 mL). The aqueous phase was extracted two times with dichloromethane (2x20 mL) and the combined organic layers were dried over Na 2 SO 4 and concentrated under reduced pressure.

Screening of reaction conditions
The crude mixture was dissolved in 3 mL MeOH, whereupon LiOH (14.5 mg, 0.6 mmol, 2 equiv) was added and the reaction was stirred at room temperature. After completion, HCl (1.25 M) in MeOH (0.5 mL) was added and MeOH was removed under reduced pressure.
Column chromatography purification on silica provided the pure products (eluent: dichloromethane : MeOH).
Afterwards, the reaction was diluted with dichloromethane, slowly neutralized with NaOH

Control experiments
All control experiments were performed according to the optimized conditions described in the manuscript (table 2)