Wydział Chemii

Md. Mahbubur Rahman

Daniel J. Pyle

Elwira Bisz

Błażej Dziuk

Krzysztof Ejsmont

Roger Lalancette

Qi Wang

Hao Chen

Roman Szostak

Michal Szostak

2021

Journal of Organic Chemistry

86

10455-10466

10.1021/acs.joc.1c01110

Naukowa

Angielski

Artykuł

The development of efficient methods for facilitating N–C(O) bond activation in amides is an important objective in organic synthesis that permits the manipulation of the traditionally unreactive amide bonds. Herein, we report a comparative evaluation of a series of cyclic amides as activating groups in amide N–C(O) bond cross-coupling. Evaluation of N-acyl-imides, N-acyl-lactams, and N-acyl-oxazolidinones bearing five- and six-membered rings using Pd(II)–NHC and Pd–phosphine systems reveals the relative reactivity order of N-activating groups in Suzuki–Miyaura cross-coupling. The reactivity of activated phenolic esters and thioesters is evaluated for comparison in O–C(O) and S–C(O) cross-coupling under the same reaction conditions. Most notably, the study reveals N-acyl-δ-valerolactams as a highly effective class of mono-N-acyl-activated amide precursors in cross-coupling. The X-ray structure of the model N-acyl-δ-valerolactam is characterized by an additive Winkler–Dunitz distortion parameter Σ(τ+χ_N) of 54.0°, placing this amide in a medium distortion range of twisted amides. Computational studies provide insight into the structural and energetic parameters of the amide bond, including amidic resonance, N/O-protonation aptitude, and the rotational barrier around the N–C(O) axis. This class of N-acyl-lactams will be a valuable addition to the growing portfolio of amide electrophiles for cross-coupling reactions by acyl–metal intermediates.

Mixtures, Amides, Organic compounds, Reactivity, Cross coupling reaction

http://dx.doi.org/10.1021/acs.joc.1c01110

https://www.acs.org/content/acs/en.html