New stabilising groups for lateral lithiation of ortho-cresol derivatives من كتب علمية

New stabilising groups for lateral lithiation of orthocresol derivatives من كتب علمية 
James A. Wilkinson

New stabilising groups for lateral lithiation of ortho-cresol derivatives
and a new route to 2-substituted chromans
James A. Wilkinson *, Eun-Ang Raiber, Sylvie Ducki
Centre for Molecular Drug Design, Biosciences Research Institute, Cockcroft Building, University of Salford, Salford M5 4WT, UK
a r t i c l e i n f o
Article history:
Received 30 January 2008
Received in revised form 4 April 2008
Accepted 24 April 2008
Available online 29 April 2008
Keywords:
Lateral lithiation
Alkylation
ortho-Cresol
Chromans
a b s t r a c t
2-(2-Methoxyethoxy)-toluene and 2-(2-dimethylaminoethoxy)-toluene have been lithiated using sec-
BuLi under a variety of conditions and the laterally lithiated species trapped with electrophiles, including
but-1-ene oxide, leading to a new synthesis of 2-ethylchroman.
 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Lateral lithiation is an important methodology in organic synthesis.
1 Lateral lithiation of benzenoid aromatics requires a stabilising
group capable of either delocalising negative charge or
stabilising an organolithium by coordination.2 Oxygen-based stabilising
groups placed in the ortho-position have been used for
a number of lateral lithiations but are problematic in the case of
simple ortho-cresol derivatives. The methoxy group requires
superbase conditions to effect deprotonation and the methoxymethyl
group gives exclusive ortho-lithiation (Scheme 1).3
In a previous work on diarylmethane derivatives we have used
the methoxyethoxy group in efficient lateral lithiations.4 This led us
to investigate the use of the same group as a potentially more
efficient stabiliser for lateral lithiation of ortho-cresol derivatives.
We have recently reported lateral lithiation reactions of orthocresol
derivatives using both the methoxyethoxy and dimethylaminoethoxy
stabilising groups.5 Here, we report in full the results
of these investigations