Configurational Stability of Lithiated Aryloxiranes
FULL PAPER
action times (less than 30 s, Table 2, Schemes 11 and 12) proved to be re-
producible within the error limits of 5%.
mization occurs only slowly”, in the words of Haeffner
et al.,[5c] could also be accomplished in the case of lithiated
styrene oxides by carrying out their deprotonation reactions
under certain experimental conditions (e.g., THF/TMEDA)
and by modulating the temperature. This may also be of in-
terest for establishing fruitful and efficient dynamic resolu-
tions starting from racemic epoxides. This issue is currently
being investigated in our laboratory.
Lithiation/deuteration of optically active epoxides—general procedure:
Standard solutions (0.05m) of the respective optically active epoxide
(0.1 mmol in 2 mL of dry solvent) and TMEDA (when required;
0.1 mmol) were cooled to the fixed temperature and treated with sBuLi
(0.15 mmol, 1.3m solution in cyclohexane) under N2. After stirring the re-
sulting mixture for the given time (see the main text and Supporting In-
formation), MeOD (10 mmol) was added. The cooling bath was removed
and the reaction mixture was allowed to warm to room temperature,
then diluted with brine (5 mL) and extracted with Et2O (3ꢃ5 mL). The
combined organic phases were dried over Na2SO4 and concentrated in
vacuo. The crude product was analyzed without further purification to
determine the enantiomeric ratio as described above.
Experimental Section
General: Tetrahydrofuran (THF), pentane, and hexane were freshly dis-
tilled under nitrogen, THF over sodium/benzophenone ketyl, and pen-
tane and hexane over calcium hydride. For the 1H and 13C NMR spectra
(1H NMR: 600 MHz; 13C NMR: 150 MHz, Bruker Avance 600), CDCl3
was used as solvent. GC-MS analyses were performed on a HP 5890 gas
chromatograph (dimethylsilicon capillary column, 30 m, 0.25 mm i.d.)
equipped with a mass selective detector operating at 70 eV (EI). Optical
rotations were measured with a Perkin-Elmer 341 polarimeter using a
cell of 1 dm pathlength at 258C; the concentration (c) is expressed in g/
100 mL. Analytical thin-layer chromatography (TLC) was carried out on
precoated 0.25 mm thick plates of Kieselgel 60 F254; visualization was
accomplished by using UV light (254 nm) or by spraying with a solution
Acknowledgements
This work was carried out under the framework of the National Project
“Stereoselezione in Sintesi Organica. Metodologie ed Applicazioni” and
financially supported by the University of Bari and by the Interuniversity
Consortium C.I.N.M.P.I.S. The authors would like to acknowledge Dr.
Valentina Mallardo for her contribution to the Experimental Section.
of 5% (w/v) ammonium molybdate and 0.2% (w/v) ceriumACTHNUTRGNE(NUG III) sulfate in
Chemistry of Organolithium Compounds, Vol. 2 (Eds.: Z. Rappo-
port, I. Marek), Wiley, New York, 2004, Chapter 13; d) V. Capriati,
f) J. L. Stymiest, V. Bagutski, R. M. French, V. K. Aggarwal, Nature
[2] The dichotomous reactivity of lithiated styrene oxide has been re-
cently investigated by NMR and DFT calculations: V. Capriati, S.
Florio, F. M. Perna, A. Salomone, A. Abbotto, M. Amedjkouh, S. O.
[3] R. E. Gawley in Topics in Stereochemistry, Vol. 26: Stereochemical
Aspects of Organolithium Compounds (Eds.: R. E. Gawley, J.
Siegel), Wiley-VCH, Weinheim, 2010, Chapter 3.
[4] a) J. Clayden, Tetrahedron Organic Chemistry Series, Vol 26: Orga-
nolithiums: Selectivity for Synthesis (Eds.: J. E. Baldwin, R. M. Wil-
liams) Pergamon, Amsterdam, 2002; b) P. Beak, T. A. Johnson,
D. D. Kim, S. H. Lim in Topics in Organometallic Chemistry, Vol. 5:
Organolithiums in Enantioselective Synthesis (Ed.: D. M. Hodgson),
Springer, Heidelberg, 2003, pp. 139–176; c) D. Hoppe, F. Marr, M.
Brꢄgemann in Topics in Organometallic Chemistry, Vol. 5: Organo-
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[5] For leading references tackling the relationship between configura-
tional stability and aggregation, see: a) H. J. Reich, M. A. Medina,
48–49; e) V. Capriati, S. Florio, R. Luisi, F. M. Perna, A. Spina, J.
100 mL of a 17.6% (w/v) aqueous solution of sulfuric acid and heating at
473 K for some time until blue spots appeared. All reactions involving
air-sensitive reagents were performed under nitrogen in oven-dried glass-
ware using the syringe/septum cap technique. Lithiation/deuteration re-
ACHTUNGTRENNUNGactions were performed in an ethanol/liquid N2 (157 K), methanol/liquid
N2 (175 K), acetone/liquid N2 (183 K), diethyl ether/dry ice (190 K), or
acetone/dry ice (195 K) cold bath. The enantiomeric ratios were deter-
mined as follows: compound (S)-16 by 1H NMR analysis (600 MHz,
CDCl3) in the presence of the Mosher acid ((R)-(+)-3,3,3-trifluoro-2-me-
thoxy-2-phenylpropanoic acid;[32] molar ratio of the Mosher acid/16, 1:1),
compounds 8–10 by HPLC analysis employing a Daicel Chiralcel OD-H
column (250ꢃ4.6 mm), compounds 1, 2, 4–6, 11, 12, and 14 by HPLC
analysis (HPLC: pump 1525, detector 996 PDA) employing a Cellulose
Lux-2 column (250ꢃ4.6 mm), and compounds 3 and 7 by GC analysis
(HP 6890) employing a Chirasil-DEX CB column (250ꢃ0.25 mm, column
head pressure 18 psi, He flow 1.5 mLminꢀ1, oven temperature 100–
1108C). Racemic oxiranes were prepared by either the Corey–Chaykov-
sky epoxidation procedure[33] starting from the corresponding benzalde-
hyde derivatives (epoxides 2, 4–8, and 12) or the methodology of Durst
and co-workers[34] (epoxides 1 and 3). The optically active epoxides 1–8
and 12 were synthesized as follows: compounds 2, 4–7, and 12 starting
from the corresponding racemic mixtures by using Jacobsen and co-work-
ersꢂ hydrolytic kinetic resolution[35] and compounds 1, 3, and 8 starting
from the corresponding a-chloro ketones[36] exploiting Noyoriꢂs asymmet-
ric reduction. a-Chloro ketones were prepared from the commercially
available acetophenone derivatives following reported procedures.[37]
Racemic and optically active oxiranes 9–11 and 14 were prepared from
racemic or optically active 4-(bromophenyl)oxiranes (12) according to
previously reported procedures.[27] The spectroscopic data of epoxides
1,[38] 2,[38] 3,[39] 4,[35] 5,[35] 6,[35] 7,[40] 8,[41] 9,[27] 10,[27] 12,[40] 14[27] and of amino
alcohol 16[27] have been reported previously. For the spectroscopic data
of compound 11 see the Supporting Information.
Kinetic studies: All the kinetic experiments were conducted in a closed
vessel immersed in the appropriate cold bath for the temperature em-
ployed (see above). The temperatures were monitored by using a cali-
brated digital thermometer. The rate constants for the racemization of
optically active oxiranylithiums were determined by plotting enantiomer-
ic ratios against time after performing a series of lithiation/deuteration
experiments on the corresponding epoxides at different temperatures and
times as reported in the main text. Each point in the plot corresponds to
a single experiment. The enantiomeric ratios determined at very short re-
[6] a) H. Ott, C. Dꢅschlein, D. Leusser, D. Schildbach, T. Seibel, D.
b) H. Ott, U. Pieper, D. Leusser, U. Flierler, J. Henn, D. Stalke,
Chem. Eur. J. 2011, 17, 8216 – 8225
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