Sébastien Alazet

Base‐Catalyzed Electrophilic Trifluoromethylthiolation of Terminal Alkynes

[*] S. Alazet, Dr. T. BillardInstitute of Chemistry and Biochemistry (ICBMS—UMR CNRS5246), Universit de Lyon, Universit Lyon 1, CNRS43 Bd du 11 novembre 1918, 69622 Lyon (France)E-mail: Thierry.billard@univ-lyon1.frS. Alazet, Prof. L. Zimmer, Dr. T. BillardCERMEP—in vivo imaging, Groupement Hospitalier Est59 Bd Pinel, 69003 Lyon (France)Prof. L. ZimmerLyon Neuroscience Research Center (UMR CNRS 5292, UMRINSERM 1028), Groupement Hospitalier Est59 Bd Pinel, 69003 Lyon (France)[**] We thank the CNRS and the French Ministry of Research for theirfinancial supports. The French Fluorine Network is also thanked forits support.Supporting information for this article is available on the WWWunder http://dx.doi.org/10.1002/anie.201305179.

Electrophilic Trifluoromethylthiolation of Carbonyl Compounds

A general method for the α-trifluoromethylthiolation of carbonyl compounds, without prefunctionalization, has been developed. Aldehydes, ketones, esters, amides, keto-esters, alkaloids, and steroids have been trifluoromethylthiolated with good yields. This work, proposing a new reagent for electrophilic trifluoromethylthiolation, provides a route towards the original synthesis of various trifluoromethylthiolated molecules for further applications.

Mild and Soft Catalyzed Trifluoromethylthiolation of Boronic Acids: The Crucial Role of Water

The most reactive 2nd generation of trifluoromethanesulfenamides undergoes a copper-catalyzed cross-coupling reaction with boronic acids to afford CF3 S-molecules. Contrary to the previous methods in the literature, no base addition, no heating, and no large excess of reagents are required to obtain good results. Furthermore, a crucial role of a small amount of water to favor this reaction has been demonstrated. This constitutes the mildest described conditions for such a reaction.

Superacid-Catalyzed Trifluoromethylthiolation of Aromatic Amines

Upon activation under superacid conditions, functionalized tailor-made N-SCF3 sulfenamides served as reagents for the trifluoromethylthiolation of aromatic amines. This method has a broad substrate scope and can be used for the late-stage functionalization of complex molecules such as alkaloids or steroids. Mechanistic studies based on in situ low-temperature NMR spectroscopy revealed the involvement of dicationic superelectrophilic intermediates.

Copper-Catalyzed Perfluoroalkylthiolation of Alkynes with Perfluoroalkanesulfenamides.

Copper-catalyzed direct perfluoroalkylthiolation of alkynes by using the corresponding perfluoroalkanesulfenamide reagent is reported. The selective mono- and bis-perfluoroalkylthiolation of alkynes can be conducted under very mild conditions (no base, room temperature) in very good to excellent yields. This approach, which uses a low toxicity, inexpensive copper catalyst that incorporates a commercially available ligand, is applied in the absence of any additional base. Preliminary mechanistic investigations shed some light on the nature of the unprecedented reactivity observed.

Frontispiece: Mild and Soft Catalyzed Trifluoromethylthiolation of Boronic Acids: The Crucial Role of Water

Wet Boronic Trifluoromethylthiolation Due to their high lipophilicity, trifluoromethylthiolated molecules play an important role in various fields, in particular in life sciences. Trifluoromethylthiolation of boronic acids with a highly efficient reagent is described to obtain aromatic and vinylic trifluoromethylthiolated compounds very easily and without any specific practical skills. The crucial role of a small amount of water has been demonstrated to obtain good results. For more details see the Communication by T. Billard et al. on page 14694 ff.