BF₃·SMe₂ for Thiomethylation, Nitro Reduction and Tandem Reduction/SMe Insertion of Nitrogen Heterocycles

Abstract

Herein, a general, solvent‐free and straightforward thiomethylation of electron deficient heterocycles using BF3·SMe2 as a dual thiomethyl source and Lewis acidic activator is presented. A range of heterocycles including pyrimidine, pyrazine, pyridazine, thiazole and purine derivatives were successfully substituted using this method. An unexpected reductive property of BF3·SMe2 towards nitropyridines was also discovered including an intriguing tandem reduction/SMe insertion process in certain substrates. Notable features of the present work include its convenience and use of a non‐malodorous reagent while the discovery of novel chemical transformations using BF3·SMe2 provides fundamental new insights into the reactivity of this commonly employed reagent.

Synthesis of Phenols from Aryl Ammonium Salts under Mild Conditions

“…13 C­{ 1 H} NMR (101 MHz, DMSO- d ) δ 164.1, 147.4, 142.6, 115.3, 108.9. All spectral data match those previously reported …”

“…All spectral data match those previously reported. 33 Synthesis of 2-Hydroxy-5-iodopyridine (20). Following the general procedure, the crude product was purified using silica gel column chromatography (DCM−MeOH = 20:1) to produce the desired product 20; 20 was isolated as a white solid (236 mg, 89% yield); 1 H NMR (400 MHz, DMSO-d) δ 11.72 (s, 1H), 7.67 (d, J = 2.2 Hz, 1H), 7.58 (dd, J = 9.5, 2.3 Hz, 1H), 6.23 (d, J = 9.5 Hz, 1H).…”

Thioacetalation and Multi-Component Thiomethylative Friedel-Crafts Arylation Using BF3SMe2

“…The combined boron trifluoride complex has since been used almost exclusively for ether dealkylations. − Some developments toward uses of the complex have nonetheless been accomplished, such as selective cleavage of di- tert- butylsilylene ethers, selective methoxy cleavage, and as a borylation reagent . Recently, we reported BF 3 SMe 2 as a convenient thiomethylating reagent and also showed that it could reduce nitro groups in certain substrates . During our investigation, we also found that BF 3 SMe 2 could produce methyl-dithioacetals from aldehydes albeit in a single example and in low yield.…”

“…1 H NMR (400 MHz, CDCl 3 ) δ 8.96 (d, J = 2.3 Hz, 1H), 8.16 (d, J = 2.3 Hz, 1H), 8.13–8.06 (m, 1H), 7.82 (dd, J = 8.2, 1.4 Hz, 1H), 7.71 (ddd, J = 8.2, 6.9, 1.4 Hz, 1H), 7.55 (ddd, J = 8.2, 6.9, 1.4 Hz, 1H), 4.99 (s, 1H), 2.14 (s, 6H). 13 C­{ 1 H} NMR (101 MHz, CDCl 3 ) δ 150.8, 147.7, 133.9, 132.6, 129.7, 129.4, 128.0, 127.5, 127.2, 54.1, 14.9 …”

Convergent synthesis of 2-thioether-substituted (N)-methanocarba-adenosines as purine receptor agonists

“…Data matched with the literature report. 28 1 H NMR (400 MHz, DMSO-d 6 ) d 12.76 (s, 1H), 7.97 (s, 1H), 7.18 (s, 2H), 2.44 (s, 3H). Yield: 67%; 3.80 g of 16a from 5.30 g of 2-chloroadenine (9).…”