Optional ortho and lateral lithiations of4,4-dimethyl-2-(o-tolyl)oxazolines من كتب علمية

Optional ortho and lateral lithiations of4,4dimethyl2(otolyl)oxazolines من كتب علمية 

Optional ortho and lateral lithiations of
4,4-dimethyl-2-(o-tolyl)oxazolines
Naruki Tahara, Tsutomu Fukuda and Masatomo Iwao*
Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1 -14 Bunkyo-machi, Nagasaki 852 -8521, Japan
Received 5 September 2002; revised 9 October 2002; accepted 11 October 2002
Abstract—4,4-Dimethyl-2-(o-tolyl)oxazolines 1 undergo normal lateral lithiation at the benzylic position by treatment with
sec-BuLi in diethyl ether at −78°C. In contrast, metalation of 1 with sec-BuLi/TMEDA in diethyl ether at the same temperature
leads to ortho-lithiation at the 6
-position. Rationalization for the unusual ortho-lithiation of 1 is proposed. © 2002 Elsevier
Science Ltd. All rights reserved.
Directed lithiation has been recognized as an excellent
method for the synthesis of regiospecifically substituted
aromatic compounds.1 The lithiation of benzene derivatives
occurs selectively at the ortho-position to a directing
group (ortho-lithiation). However, if a methyl group
exists at the ortho-position to the directing group,
deprotonation proceeds at the adjacent-benzylic position
preferentially due to intrinsic high acidity of the
benzylic protons (lateral lithiation).2 The lateral lithiation
is especially facile for o-toluic acid and derivatives,
such as esters, amides, nitriles, and 2-oxazolines.2 This
may be rationalized by the additional stabilization of
the benzylic anion by its extended delocalization to the
carbonyl (or its equivalent) moiety. The lateral lithiation
of 4,4-dimethyl-2-(o-tolyl)oxazoline (1a) has been
reported by Gschwend and Hamden.3 We have reinvestigated
this reaction and discovered very unusual ortholithiation
of 1a (Scheme 1).4 Herein, we report this
interesting finding.