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Is the Elimination of Lithium Alkoxide Easier from a Vinyllithium or from an Alkyllithium? A DFT Study of the Aromatization of 3‐Vinylidene‐2,3‐dihydrobenzofurans to Benzofurans
Author(s) -
Fressigné Catherine,
Girard AnneLise,
Durandetti Muriel,
Maddaluno Jacques
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200800828
Subject(s) - chemistry , alkoxide , deprotonation , lithium (medication) , methoxide , propargyl , medicinal chemistry , structural isomer , triple bond , isomerization , computational chemistry , ether , stereochemistry , photochemistry , methanol , double bond , organic chemistry , catalysis , medicine , ion , endocrinology
A possible mechanism for the last step of a cascade transformation in which lithiated propargyl ether 2 is converted into 3‐vinylbenzofuran 7 is described. Starting from the lithiated E olefin 3A , our DFT computations show that the final departure of lithium alkoxide is not easy unless an excess of n BuLi, the importance of which has been noted experimentally, prompts a second deprotonation. This theoretical evidence was further supported by a complementary experiment involving dihydrobenzofuran 10 . The deprotonation of this latter compound by n BuLi elicits a spontaneous syn elimination, probably through monolithiated intermediates 10Li and 6 , regioisomers of 3A . The activation barriers calculated for these various transformations indicate that the elimination of lithium methoxide from β‐lithiated acetals requires around 10 times more energy when the precursor is a vinyllithium rather than an alkyllithium. A route passing through a sigmatropic rearrangement was also considered. This triggers the elimination of a molecule of methanol, which acts as a shuttle to transfer a proton from the heterocycle to the vinyl position. However, with the set of reaction coordinates considered, this mechanism passes through high‐lying activation barriers unless the conformation of the exocyclic double bond in 3 is Z (isomer 3B ).(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)