Chemo‐ and Enantioselective Insertion of Furyl Carbene into the N−H Bond of 2‐Pyridones

Abstract

Asymmetric carbene insertion reactions represent one of the most important protocols to construct carbonheteroatom bonds. The use of donor-acceptor diazo compounds bearing an ester group is however a prerequisite for achieving high enantioselectivity. Herein, we report a chemoand enantioselective formal N À H insertion of 2-pyridones that has been accomplished for the first time with enynones as the donor-donor carbene precursors. DFT calculations indicate an unprecedented enantioselective 1,4-proton transfer from O to C. The rhodium catalyst provides a chiral pocket in which the steric repulsion and the p-p interaction of the propeller ligand play a critical role in determining the selectivities.

Accessing Functionalized Furans from Reacting Enynones and Enynals through Furyl Metal Carbenes

“…The same group developed a rhodium(II)‐catalyzed chemo‐ and enantioselective process, yielding chiral N ‐furfuryl 2‐pyridones 5 , using enynones 1 and 2‐pyridones 4 (Scheme 4). [14] In these reactions, furyl−carbene insertion reaction into N−H bonds of 2‐pyridones 4 was observed rather than O−H bond insertion. DFT calculations revealed an unusual enantioselective 1,4‐proton transfer from O to C. Free‐energy calculations comparing 2‐pyridone 4 a with its tautomer, 2‐hydroxypyridine 4 a’ and examining the transition states of two possible alkylation pathways ( TS‐I and TS‐I′ ) indicated a higher stability for tautomer 4 a′ than 2‐pyridone 4 a , and a preference for O ‐alkylation upon nucleophilic addition.…”