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Sterically Controlled Pd-Catalyzed Chemoselective Ketone Synthesis via N-C Cleavage in Twisted Amides

Guangrong Meng and Michal Szostak*

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

G. Meng, M. Szostak, Org. Lett., 2015, 17, 4364-4367.

DOI: 10.1021/acs.orglett.5b02209


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Abstract

A highly chemoselective, palladium(0)-catalyzed, direct cross-coupling between boronic acids and geometrically activated amides shows excellent functional group tolerance, and delivers the versatile ketone products in high yields. Notably, the method provides direct access to acyl-metal intermediates from sterically distorted, bench-stable amide precursors under mild catalytic conditions.

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General procedure for the cross-coupling

An oven-dried vial equipped with a stir bar was charged with an amide substrate (1.0 equiv), potassium carbonate (typically, 2.5 equiv), boric acid (typically, 2.0 equiv), boronic acid (typically, 1.2 equiv), Pd(OAc)2 (typically, 0.03 equiv), and PCyHBF4 (typically, 0.12 equiv), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under high vacuum. Tetrahydrofuran (typically, 0.8 mL) was added with vigorous stirring at room temperature, the reaction mixture was placed in a preheated oil bath at 65 °C, and stirred for the indicated time at 65 °C. After the indicated time, the reaction mixture was cooled down to room temperature, diluted with CH2Cl2 (10 mL), filtered, and concentrated. The sample was analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain selectivity, conversion and yield using internal standard and comparison with authentic samples. Unless stated otherwise, purification by chromatography on silica gel afforded the title product.


Evaluation of Cyclic Amides as Activating Groups in N-C Bond Cross-Coupling: Discovery of N-Acyl-δ-valerolactams as Effective Twisted Amide Precursors for Cross-Coupling Reactions

Md. M. Rahman, D. J. Pyle, E. Bisz, B. Dziuk, K. Ejsmont, R. Lalancette, Q. Wang, H. Chen, R. Szostak, M. Szostak, J. Org. Chem., 2021, 86, 10455-10466.

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.


Key Words

ayl ketones


ID: J54-Y2015