TY - JOUR
T1 - Electrostatic Switching between S N 1 and S N 2 Pathways
AU - Yu, Li Juan
AU - Coote, Michelle L.
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2019/1/17
Y1 - 2019/1/17
N2 - A test set 264 nucleophilic substitution reactions was studied via accurate quantum chemical reactions to establish the relative preferences for S N 1 versus S N 2 mechanisms. In low polar solvents, reactions involving anionic nucleophiles and leaving groups favored S N 2 pathways. In contrast, S N 1 is preferred for those reactions involving neutral nucleophiles and leaving groups except where the carbocation intermediates are exceptionally unstable. For neutral nucleophiles and anionic leaving groups, S N 2 is generally preferred over S N 1 except for exceptionally stable carbocation intermediates. On the basis of these studies, candidate reactions for which distinct S N 1 or S N 2 preferences could be reversed by electric fields were selected. As proof of concept, the S N 1/S N 2 preferences for the reaction of tBu-triflate with pyridine (S N 2 to S N 1) and with piperidine (S N 1 to S N 2) were switched by both charged functional groups and point charges (i.e., electric fields) along the reaction axis, with a positive charge on the nucleophile side favoring S N 1 and a negative charge favoring S N 2 for these reactions.
AB - A test set 264 nucleophilic substitution reactions was studied via accurate quantum chemical reactions to establish the relative preferences for S N 1 versus S N 2 mechanisms. In low polar solvents, reactions involving anionic nucleophiles and leaving groups favored S N 2 pathways. In contrast, S N 1 is preferred for those reactions involving neutral nucleophiles and leaving groups except where the carbocation intermediates are exceptionally unstable. For neutral nucleophiles and anionic leaving groups, S N 2 is generally preferred over S N 1 except for exceptionally stable carbocation intermediates. On the basis of these studies, candidate reactions for which distinct S N 1 or S N 2 preferences could be reversed by electric fields were selected. As proof of concept, the S N 1/S N 2 preferences for the reaction of tBu-triflate with pyridine (S N 2 to S N 1) and with piperidine (S N 1 to S N 2) were switched by both charged functional groups and point charges (i.e., electric fields) along the reaction axis, with a positive charge on the nucleophile side favoring S N 1 and a negative charge favoring S N 2 for these reactions.
UR - http://www.scopus.com/inward/record.url?scp=85059621616&partnerID=8YFLogxK
U2 - 10.1021/acs.jpca.8b11579
DO - 10.1021/acs.jpca.8b11579
M3 - Article
SN - 1089-5639
VL - 123
SP - 582
EP - 589
JO - Journal of Physical Chemistry A
JF - Journal of Physical Chemistry A
IS - 2
ER -