Triflamides: Highly Reactive, Electronically Activated N-Sulfonyl Amides in Catalytic N-C(O) Amide Cross-Coupling

Shicheng Shi, Roger Lalancette, Roman Szostak, Michal Szostak*

*Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States, Email: michal.szostakrutgers.edu

S. Shi, R. Lalancette, R. Szostak, M. Szostak, Org. Lett., 2019, 21, 1253-1257.

DOI: 10.1021/acs.orglett.8b03901

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Abstract

A highly chemoselective Suzuki-Miyaura cross-coupling of trifluoromethanesulfonamides (triflamides) accomplishes a direct synthesis of ketones under mild conditions as a powerful alternative to the Weinreb ketone synthesis.

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General Procedure for the Suzuki-Miyaura Cross-Coupling

An oven-dried vial equipped with a stir bar was charged with a triflamide substrate (neat, 1.0 equiv), potassium carbonate (typically, 3.0 equiv), boronic acid (typically, 2.0 equiv), Pd-NHC precatalyst (typically, 3 mol%) and H₂O (typically, 5.0 equiv), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. THF (typically, 0.25 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 40 °C and stirred for the indicated time. After the indicated time, the reaction mixture was cooled down to room temperature, diluted with CH₂Cl₂ (10 mL), filtered, and concentrated. A sample was analyzed by ¹H NMR (CDCl₃, 500 MHz) and/or GC-MS to obtain conversion, selectivity and yield using internal standard and comparison with authentic samples. Purification by chromatography on silica gel (EtOAc/hexanes) afforded the title product.

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[(NHC)PdCl₂(Aniline)] Complexes: Easily Synthesized, Highly Active Pd(II)-NHC Precatalysts for Cross-Coupling Reactions

Q. Xia, S. Shi, P. Gao, R. Lalancette, R. Szostak, M. Szostak, J. Org. Chem., 2021, 86, 15650-15657.

General Method for the Suzuki-Miyaura Cross-Coupling of Primary Amide-Derived Electrophiles Enabled by [Pd(NHC)(cin)Cl] at Room Temperature

P. Lei, G. Meng, Y. Ling, J. An, S. P. Nolan, M. Szostak, Org. Lett., 2017, 19, 6510-6513.

Pd-PEPPSI: Pd-NHC Precatalyst for Suzuki-Miyaura Cross-Coupling Reactions of Amides

P. Lei, G. Meng, Y. Ling, J. An, M. Szostak, J. Org. Chem., 2017, 82, 6638-6646.

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Key Words

Suzuki coupling, aryl ketones

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ID: J54-Y2019