Metalation of 2-Heterosubstituted Naphthalenes at the 1- or 3-Position: Factors That May Determine the Regiochemistry
Upon metalation and subsequent electrophilic trapping, 2-fluoronaphthalene inevitably gives rise to regioisomeric mixtures in varying proportions, whereas 2-(trifluoromethyl) naphthalene undergoes deprotonation either at the 1- or the 3-position, depending on the choice of the reagent. On the other hand, 2-(trifluoromethoxy) naphthalene and 2-methoxynaphthalene react exclusively at the 3-position when, respectively, sec-butyllithium and superbasic reagents are employed. Steric repulsion by the peri hydrogen in combination with crowding due to coordination of the lithium atom with the methoxy group disfavors attack at the 1-position.
WOS:000276909600019
2010
9
1531
1535
REVIEWED
EPFL