In:
Organic Chemistry Frontiers, Royal Society of Chemistry (RSC), Vol. 9, No. 19 ( 2022), p. 5168-5177
Abstract:
The transition-metal-catalyzed oxidative cyclization of diynes can be exploited to synthesize N-heterocycles, which are important structural motifs found in drug candidates and biologically active compounds. Herein, the mechanisms and origin of the chemoselectivity of Cu( i )- and Au( i )-catalyzed oxidation of diynes for the divergent syntheses of two different N-heterocycles, substituted pyrroles and dihydroindeno[1,2- c ]pyrrol-3(2 H )-ones, respectively, were elucidated using density functional theory (DFT). The DFT results reveal that the active catalytic species of the Cu(CH 3 CN) 4 BF 4 catalyst in the developed Cu( i )-catalysis system is likely to be a cationic Cu( i ) complex, which preferentially simultaneously coordinates to the two CC bonds and the nitrogen atom of the amide directing group of the diyne to generate a precursor. In contrast, the Au( i ) species preferentially binds to the electron-rich amide-tethered CC bond of the diyne, and thus produces a precursor sufficiently different from that of the Cu( i )-catalyzed pathway that two discrete reaction pathways result, leading to different products. Both catalyses involve the following steps: substrate activation, N -oxidant attack, N–O bond cleavage, five-membered cyclization, carbene migration, H-shift, and substrate exchange. The difference between the two systems is that the Au( i )-catalysis can undergo another intramolecular five-membered cyclization, whereas the Cu( i )-catalysis cannot. This research provides a detailed mechanism and information on the chemoselectivity of the transition metal-catalyzed oxidative cyclization of diynes, which will be useful for understanding and designing novel transition metal-catalyzed reactions of diynes.
Type of Medium:
Online Resource
ISSN:
2052-4129
Language:
English
Publisher:
Royal Society of Chemistry (RSC)
Publication Date:
2022
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