A theoretical study on the elimination reaction of acrylonitrile from 2′-O-cyanoethylated nucleosides by Bu4NF. Issue 1 (3rd January 2019)

• Record Type: Journal Article
• Authors: Ando, Kaori; Saneyoshi, Hisao; Seio, Kohji; Sekine, Mitsuo
• Is Part Of: Tetrahedron. Volume 75:Issue 1(2019)
• Page Start: 1
• Page End: 9
• Publication Date: 2019-01-03
• Subjects: Elimination reaction -- Computational study -- Syn-periplanar -- F− -- Atomic charges -- 2′-protecting group of RNA derivatives; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2018.11.042
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The elimination reaction of acrylonitrile from 2′- O -cyanoethylated nucleosides by Bu4 NF was studied computationally. The transition structures for the reaction of 3-methoxypropionitrile with Me4 NF were located at the MP2, B3LYP, and B3LYP-SCRF(Dipole) levels with 6-31 + G* basis set. The α-hydrogen of the cyano group was removed via a proton transfer from the α-carbon to the oxygen with a syn -periplanar arrangement rather than the deprotonation reaction with F − . In the presence of an excess amount of Me4 NF, the activation energy decreased by the coordination of Me4 N + to the cyano group. The reaction of 3-methoxypropionitrile with Bu4 NF and 2′- O -cyanoethylated uridine with Me4 NF also occurred via a proton transfer mechanism with lower activation energies. The reactivity tendency corresponds to the amount of the negative charge on the oxygen atom and part of the reason for the faster elimination with F − rather than with DBU concerns entropy. The experimental results are well explained by these calculations. Graphical abstract: