Sterically Hindered Ketones via Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Amides by N-C(O) Activation
Chengwei Liu, Roger Lalancette, Roman Szostak and Michal Szostak*
*Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States,
Email: michal.szostak
rutgers.edu
C. Liu, R. Lalancette, R. Szostak, M. Szostak, Org. Lett., 2019, 21, 7976-7981.
DOI: 10.1021/acs.orglett.9b02961
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Abstract
A palladium-catalyzed Suzuki-Miyaura cross-coupling of unconventional amide electrophiles enables a synthesis of sterically hindered ketones via a selective N-C(O) activation. Mechanistic studies demonstrate that steric bulk on the amide has a major impact, which is opposite to the traditional Suzuki-Miyaura cross-coupling of sterically hindered aryl halides.
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General Procedure for the Synthesis of Sterically Hindered Ketones via Suzuki-Miyaura
Cross-Coupling of Amides. An oven-dried vial equipped with a stir bar was charged with an amide substrate (neat, 1.0 equiv), boronic acid (typically, 2.0 equiv), Pd(OAc)2 (typically, 3 mol%), PCy3HBF4 (typically, 12 mol%), Na2CO3 (typically, 2.5 equiv), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. Dioxane (typically, 0.125 M) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 120 °C, and stirred for the indicated time at 120 °C. After the indicated time, the reaction mixture was diluted with CH2Cl2 (10 mL), filtered, and concentrated. The sample was analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain conversion, yield and selectivity using internal standard and comparison with authentic samples. Purification by chromatography on silica gel (hexanes/ethyl acetate) afforded the title product
Key Words
ID: J54-Y2019
