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Conclusions
We have demonstrated that a lithiocarbanion generated
by deprotonation between phenyl and alkenyl groups has a
configurational stability that is sufficiently strong to be
trapped without racemization by a proton source or a car-
bon electrophile at –50 °C with the aid of a carbamoyloxy
group and that the stereochemical outcomes are affected
by changing the electrophile and solvent. The result can
be understood in terms of the existence of an equilibrium
involving a solvent-separated ion pair and three different
kinds of contact ion pairs in which the ligand coordinated
to the lithium atom differs.
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[7] The absolute configuration of 8 was determined by conversion
into a known compound (see the Supporting Information for
details).
Experimental Section
General Procedure for Electrophilic Substitution. Reaction of (S)-6
with BnBr in N-Methylmorpholine: To a cooled (–50 °C) solution
of (S)-6 (99:1 er, 50.7 mg, 0.184 mmol) in N-methylmorpholine
(1.84 mL), was added a solution of nBuLi (2.32 m in hexane,
159 μL, 0.368 mmol). The reaction mixture was stirred at the same
temperature for 5 min, then a solution of benzyl bromide in N-
methylmorpholine (2.0 m, 460 μL, 0.920 mmol) was added drop-
wise. After stirring for 10 min, the reaction mixture was quenched
with saturated aqueous NH4Cl (2 mL). The resulting mixture was
extracted with Et2O (2ϫ 5 mL), and the combined organic phases
were washed with saturated brine (3 mL), dried, and concentrated.
The residual oil was subjected to column chromatography (silica
gel 10 g; hexane/AcOEt = 9:1) to give a mixture of 7 and 8 in a
ratio of 1:0.36 (59.1 mg, 87%).
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, spectroscopic data, and copies of 1H
and 13C NMR spectra for all new compounds.
[8] The benzylation reactions of the corresponding O-methyl de-
rivative resulted in much lower conversion (10–37%) and al-
most complete racemization in all solvents.
[9] M. Seppi, R. Kalkofen, J. Reupohl, R. Fröhlich, D. Hoppe,
Angew. Chem. 2004, 116, 1447–1451; Angew. Chem. Int. Ed.
2004, 43, 1423–1424.
[10] Addition of nBuLi to a solution of (S)-6a and BnBr (5 equiv.)
at –50 °C resulted in complete recovery of (S)-6a, suggesting
that the rate of reaction of nBuLi with BnBr is much faster
than that of deprotonation of (S)-6a under the conditions.
Consequently, the possibility that deprotonation still occurs af-
ter addition of BnBr can be ruled out by the fact that (S)-6a
is not recovered from the reaction.
Acknowledgments
This research was partially supported by the Ministry of Educa-
tion, Culture, Sports, Science and Technology (MEXT) through a
Grant-in-Aid for Scientific Research (B) 22390001 (K. T.), a Grant-
in-Aid for Young Scientists (B) 22790011 (M. S.), and Grant-in-
Aid for Young Scientists (start-up) 21890151 (to H. I.). We thank
the Natural Science Center for Basic Research and Development
(N-BARD), Hiroshima University for the permission to use the
facilities.
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Tomooka, E. Gras, Organolithiums in Enantioselective Synthe-
[11] Quenching with CH3CO2D afforded the corresponding deuter-
ated product in ca. 90% D/H ratio.
[12] R. Hof, R. M. Kellogg, J. Chem. Soc. Perkin Trans. 1 1996,
2051–2060.
Received: July 4, 2011
Published Online: September 19, 2011
Eur. J. Org. Chem. 2011, 6553–6557
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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