J . Org. Chem. 1998, 63, 3295-3301
3295
1,2- vs 1,4-Regioselectivity of Lith ia ted P h en yla ceton itr ile tow a r d
r,â-Un sa tu r a ted Ca r bon yl Com p ou n d s. 2. Rela tion betw een th e
Regioselectivity a n d th e Str u ctu r e of th e Sp ecies in Solu tion
Tekla Strzalko, J acqueline Seyden-Penne, and Lya Wartski*
Institut de Chimie Mole´culaire d’Orsay, URA CNRS 478, 91405 Orsay, France
J acques Corset,* Martine Castella-Ventura, and Franc¸oise Froment
LASIR, CNRS, UPR 2631, B.P. 28, 94320 Thiais, France
Received J uly 30, 1996 (Revised Manuscript Received August 6, 1997)
In THF and THF-toluene media, the reaction of lithiated phenylacetonitrile (1) with benzylide-
neacetone (5), at low temperature, led to the same ratio of 1,2- and 1,4-adducts after 5 or 30 min
of reaction time. The concentrations of the monomeric bridged ion pair 2 preferentially formed in
THF and of the dimer of ion pairs 4 predominating in media that favor association such as THF-
toluene solvent mixtures were measured from the IR-integrated intensities of the ν (CtN) bands.
These concentrations were quantitatively related to the concentrations of the 1,2- and 1,4-adducts,
respectively. All these results evidence the kinetic control of this reaction. Intermediate complexes
that take into account the peculiar geometries of the monomer 2 and the dimer 4 are proposed to
interpret the different regioselectivities observed with 5. This study is extended to cyclic R-enones
and cinnamaldehyde. Similar trends hold for the former, while cinnamaldehyde always leads to
1,2-addition. The formation of intermediate complexes allows us to rationalize the cinnamaldehyde
behavior but is insufficient to explain the 1,4-addition with cyclic R-enones lying in an s-trans
conformation.
Sch em e 1
In tr od u ction
Carbanions R to nitriles are useful reagents for C-C
bond formation in organic synthesis. The study of the
regioselectivity of the reaction of these carbanions toward
R-enones was extensively studied by our group and
others.1,2 It was shown that different parameters such
as structures of the anionic species and R-enone, medium,
temperature, concentration, and added salts play an
important role in the 1,2- vs 1,4-addition. Lithiated
phenylacetonitrile (1) afforded 1,2- or 1,4-addition de-
pending on the experimental conditions.2 Such was also
the case for lithiated cyanohydrin ethers,3 cyanosilyl
ethers4 and phosphonitriles.5 On the other hand, lithi-
ated 3-pyridylacetonitrile2a and (N,N-dimethylamino)phe-
nylacetonitrile6 gave 1,4-addition essentially.
For a better understanding of the structural param-
eters of the anionic species that may control the 1,2- vs
1,4-regioselectivity, we have performed IR, NIR FT-
Raman, and 13C NMR spectroscopic studies of lithiated
phenylacetonitrile (1) in THF, THF-hexane, and THF-
(1) (a) Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds; Pergamon Press: London, 1991; Vol. 4. (b) Arseniyadis, S.; Kyler,
K. S.; Watt, D. S. Org. React. 1984, 31, 1-364.
toluene. We have shown that only two species are in
equilibrium in these media: a monomeric lithium-bridged
ion pair 2 and a dimeric lithium ion pair 47 (Scheme 1).
In THF, monomeric species predominates at C ) 0.25
M while dimeric species increases as the amount of
hexane or toluene in THF solution increases. Our
preliminary results have shown2a a change of the 1,2/1,4
ratio, from 95/5 in THF down to 8/92 in THF-hexane
(50/50 v/v) in the case of the reaction of 1 with benzylide-
neacetone 5 at C ) 0.25 M at -80 to -90 °C.
(2) (a) Croizat, D.; Seyden-Penne, J .; Strzalko, T.; Wartski, L.;
Corset, J .; Froment, F. J . Org. Chem. 1992, 57, 6435. (b) Strzalko, T.;
Seyden-Penne, J .; Wartski, L.; Froment, F.; Corset, J . Tetrahedron Lett.
1994, 35, 3935. (c) Sauveˆtre, R.; Roux-Schmitt, M. C.; Seyden-Penne,
J . Tetrahedron 1978, 34, 2135. (d) Roux, M. C.; Wartski, L.; Seyden-
Penne, J . Tetrahedron 1981, 37, 1927. (e) Hatzigrigoriou, E.; Wartski,
L.; Seyden-Penne, J .; Toromanoff, E. Tetrahedron 1985, 41, 5045.
(3) (a) Stork, G.; Ozorio, A. A.; Leong, A. Y. W. Tetrahedron 1978,
5175. (b) Roux, M. C. Seuron, N.; Seyden-Penne, J . Synthesis 1983,
494.
(4) Hunig, S.; Wehner, G. Chem. Ber. 1980, 113, 302.
(5) Deschamps, B. Tetrahedron 1978, 34, 2009.
(6) (a) Zervos, M.; Wartski, L.; Seyden-Penne, J . Tetrahedron 1986,
42, 4963. (b) Enders, D.; Kirchoff, J .; Mannes, D.; Raabe, G. Synthesis
1995, 659. (c) Roux, M. C.; Wartski, L.; Nierlich, M.; Lance, M.
Tetrahedron 1994, 50, 8445.
(7) Strzalko, T.; Seyden-Penne, J .; Wartski, L.; Corset, J .; Castella-
Ventura, M.; Froment, F. J . Org. Chem. 1998, 63, 3287-3294.
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Published on Web 05/15/1998