Mechanistic twist of the [8+2] cycloadditions of dienylisobenzofurans and dimethyl acetylenedicarboxylate: stepwise [8+2] versus [4+2]/[1,5]-vinyl shift mechanisms revealed through a theoretical and experimental study.
Recently, it was reported that both dienylfurans and dienylisobenzofurans could react with dimethyl acetylenedicarboxylate (DMAD) to give [8+2] cycloadducts. Understanding these [8+2] reactions will aid the design of additional [8+2] reactions, which have the potential for the synthesis of 10-membered and larger carbocycles. The present Article is aimed to understand the detailed mechanisms of the originally reported [8+2] cycloaddition reaction between dienylisobenzofurans and alkynes at the molecular level through the joint forces of computation and experiment. Density functional theory calculations at the (U)B3LYP/6-31+G(d) level suggest that the concerted [8+2] pathway between dienylisobenzofurans and alkynes is not favored. A stepwise reaction pathway involving formation of a zwitterionic intermediate for the [8+2] reactions between dienylisobenzofurans that contain electron-donating methoxy groups present in their diene moieties and DMAD has been predicted computationally. This pathway is in competition with a Diels-Alder [4+2] reaction between the furan moieties of dienylisobenzofurans and DMAD. When there is no electron-donating group present in the diene moieties of dienylisobenzofurans, the [8+2] reaction occurs through an alternative mechanism involving a [4+2] reaction between the furan moiety of the tetraene and DMAD, followed by a [1,5]-vinyl shift. This computationally predicted novel mechanism was supported experimentally.
Chen
Yuanyuan
Y
Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, College of Chemistry, Peking University, Beijing 100871, People's Republic of China.
Ye
Siyu
S
Jiao
Lei
L
Liang
Yong
Y
Sinha-Mahapatra
Dilip K
DK
Herndon
James W
JW
Yu
Zhi-Xiang
ZX
D000480:Alkynes / Q000737:chemistry*; D001572:Benzofurans / Q000737:chemistry*; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D013816:Thermodynamics; D014753:Vinyl Compounds / Q000737:chemistry*
D000480:Alkynes; D001572:Benzofurans; D014753:Vinyl Compounds; C022918:acetylenedicarboxylic acid dimethyl ester