methyllithium in diethylether. The DFT data suggest that this
pollutant is likely to seize most of the 10 mol% 3APLi in
solution. To thwart this problem, the ‘‘native’’ LiCl in MeLi
4 M. Ye, S. Logaraij, L. M. Jackman, K. Hillegass, K. A. Hirsh,
A. M. Bolliger and A. L. Grosz, Tetrahedron, 1994, 50, 6109–6116.
5
F. Pate
C. Fressigne
J. Org. Chem., 2007, 72, 6982–6991.
6 E. Hevia and R. E. Mulvey, Angew. Chem., Int. Ed., 2011, 50,
448–6450.
For recent results obtained by lithium NMR, see:
a) K. J. Kolonko, M. M. Biddle, I. A. Guzei and H. J. Reich,
´
,
N. Duguet, H. Oulyadi, A. Harrison-Marchand,
´
, J.-Y. Valnot, M.-C. Lasne and J. Maddaluno,
1
2
was first titrated by silvermetry, then trapped by three
equivalents of (S)-PhCH(CH )OLi. The resulting ‘‘cleansed’’
3
6
MeLi solution was used to repeat the experiment with 0.1
equivalent of the chiral ligand and this time, a rewarding 70%
ee was measured (entry 8). This reproducible value remains
below the 80% measured when 0.33 equiv. of a ligand is used,
probably because the fine-tuning and handling of low amounts
of water and air-sensitive aggregates is delicate at the 1–5 mmol
bench scale.
7
(
J. Am. Chem. Soc., 2009, 131, 11525–11534; (b) G. Carbone,
P. O’Brien and G. Hilmersson, J. Am. Chem. Soc., 2010, 132,
1
5445–15450; (c) J. M. Gruver, S. P. West, D. B. Collum and
R. Sarpong, J. Am. Chem. Soc., 2010, 132, 13212–13213;
d) V. Capriati and S. Florio, Chem.–Eur. J., 2010, 16,
(
4152–4162; (e) G. Kagan, W. Li, R. Hopson and P. G. Williard,
Org. Lett., 2010, 12, 520–523; (f) G. Kagan, W. Li, C. Sun,
R. Hopson and P. G. Williard, J. Org. Chem., 2011, 76, 65–70.
(a) J. F. Mc Garrity and C. A. Ogle, J. Am. Chem. Soc., 1985, 107,
1805–1810; (b) J. F. Mc Garrity, C. A. Ogle, Z. Brich and
H.-R. Loosli, J. Am. Chem. Soc., 1985, 107, 1810–1815;
In conclusion, the data presented in this communication
show that LiCl can be an ally in the enantioselective nucleo-
philic 1,2-addition of organolithium reactants to aldehydes. In
its absence, our DFT values suggest that the chiral lithium
amide used here as a chiral ‘‘ligand’’ is selectively trapped by
the alkoxide produced by the reaction, progressively hampering
its enantioselectivity. The same calculations hint at a higher
affinity between ROLi and LiCl, and explain that this salt can
act as a scavenger provided it is added at the proper time to
keep the lithium alkoxide apart from the catalytic cycle. These
matches helped us to improve a catalytic stoichiometric enantio-
selective nucleophilic 1,2-addition of an alkyllithium onto an
aldehyde and even transform it into the first sub-stoichiometric
version with marginal alteration of the ee. Obviously, the levels
of asymmetric induction now remain to be optimized and this
work is extended to other electrophiles and organolithium
reactants or additives to check if the phenomenon observed
here can be general. However, we think that the actual
procedure provides hints to fine-tune other enantioselective
processes. Otherwise, it is worth underlining that reaching
8
(
1
c) S. V. Frye, E. L. Eliel and R. Cloux, J. Am. Chem. Soc.,
987, 109, 1862–1863; (d) S. H. Bertz, C. M. Carlin,
D. A. Deadwyler, M. D. Murphy, C.A. Ogle and P. H. Seagle,
J. Am. Chem. Soc., 2002, 124, 13650–13651; (e) A. C. Jones,
A. W. Sanders, M. J. Bevan and H. J. Reich, J. Am. Chem. Soc.,
2
007, 129, 3492–3493; (f) A. C. Jones, A. W. Sanders,
W. H. Sikorski, K. L. Jansen and H. J. Reich, J. Am. Chem.
Soc., 2008, 130, 6060–6061; (g) S. E. Denmark, B. J. Williams,
B. M. Eklov, S. M. Pham and G. L. Beutner, J. Org. Chem., 2010,
7
See inter alia: (a) J. Maddaluno, A. Corruble, V. Leroux, G. Ple
5, 5558–5572.
9
´
and P. Duhamel, Tetrahedron: Asymmetry, 1992, 3, 1239–1242;
(b) A. Corruble, J.-Y. Valnot, J. Maddaluno, Y. Prigent,
D. Davoust and P. Duhamel, J. Am. Chem. Soc., 1997, 119,
10042–10048; (c) A. Corruble, D. Davoust, S. Desjardins,
C. Fressigne C. Giessner-Prettre, A. Harrison-Marchand,
´
H. Houte, M.-C. Lasne, J. Maddaluno, H. Oulyadi and
,
J.-Y. Valnot, J. Am. Chem. Soc., 2002, 124, 15267–15279;
(
d) A. Harrison-Marchand, J.-Y. Valnot, A. Corruble,
N. Duguet, H. Oulyadi, S. Desjardins, C. Fressigne and
J. Maddaluno, Pure Appl. Chem., 2006, 78, 321–331.
10 All calculations were performed with the B3P86 hybrid functional
as implemented in the Jaguar 4.1 (Schrodinger Inc. Portland,
OR-2000) software. The 6-31G** basis set, which behaved satis-
factorily in closely related situations (see for instance C. Fressigne
´
7
1
0% ee with extremely reactive reactants using no more than
1
5
0% of a cheap catalyst is groundbreaking in this field.
We thank the ‘‘Ministere de la Recherche et de la Technologie’’
¨
`
´
for B.L.’s PhD grant. The Agence Nationale pour la
Recherche supported this work (grant ANR-07-BLAN-0294-01).
Calculations have been performed at the CRIHAN
and J. Maddaluno, J. Org. Chem., 2010, 75, 1427–1436 and
references therein), was retained. The complexes relative stabilities
were calculated as the difference between the energy of the com-
plexes and the sum of the energies of their components plus the
THFs: dE = E(ALi–BLi–3THF) À E(ALi) À E(BLi) À 3E(THF).
11 For the importance of explicit microsolvation, see: (a) L. M. Pratt,
THEOCHEM, 2007, 811, 191–196; (b) L. M. Pratt, D. Jones,
A. Sease, D. Busch, E. Faluade, S. C. Nguyen and B. T. Thanh,
Int. J. Quantum Chem., 2009, 109, 34–42. For the superimposed
contribution of a continuum solvation model to the resulting
super-molecule that was not taken into account here, even if its
effect can be significant, see: ; (c) L. M. Pratt, B. Ramachandran,
J. D. Xidos, C. J. Cramer and D. G. Truhlar, J. Org. Chem., 2002,
67, 7607–7612; (d) H. K. Khartabil, P. C. Gros, Y. Fort and
(St Etienne-du-Rouvray, France). Dr N. Duguet is acknowledged
for providing (S)-PhCH(CH )OLi. We also thank Dr Peter
3
Rittmeyer (Chemetall GmbH) for discussions. This work is
dedicated to Prof. Henri Kagan on the occasion of his 80th
birthday.
Notes and references
1
(a) A. Yanagisawa, T. Kikuchi and H. Yamamoto, Synlett, 1998,
74–176; (b) G. Asensio, P. A. Aleman, J. Gil, L. R. Domingo and
M. Medio-Simon, J. Org. Chem., 1998, 63, 9342–9347;
c) L. Duhamel, P. Duhamel and J.-C. Plaquevent,
1
M. F. Ruiz-Lopez, J. Org. Chem., 2008, 73, 9393–9402;
´
(e) N. Deora and P. R. Carlier, J. Org. Chem., 2010, 75, 1061–1069.
12 B. Lecachey, H. Oulyadi, P. Lameiras, A. Harrison-Marchand,
´
(
Tetrahedron: Asymmetry, 2004, 15, 3653–3691.
(a) B. J. Bunn and N. S. Simpkins, J. Org. Chem., 1993, 58,
H. Ge
Methyllithium completely devoid of LiCl can only be prepared
from extremely toxic Hg(Me)
´
rard and J. Maddaluno, J. Org. Chem., 2010, 75, 5976–5983.
2
533–534; (b) M. Toriyama, K. Sugasawa, M. Shindo, N. Tokutake
2
.
and K. Koga, Tetrahedron Lett., 1997, 38, 567–570; (c) P. O’Brien,
J. Chem. Soc., Perkin Trans. 1, 1998, 1439–1457; (d) D. Simoni,
M. Roberti, R. Rondanin and A. P. Kozikowski, Tetrahedron
Lett., 1999, 40, 4425–4428; (e) J. M. Laumer, D. D. Kim and
P. Beak, J. Org. Chem., 2002, 67, 6797–6804; (f) B. Butler,
T. Schultz and N. S. Simpkins, Chem. Commun., 2006,
13 A stable 1 : 1 mixed aggregate lithium enolate-LDA has been
evidenced recently by Y. Ma, A. C. Hoepker, L. Gupta,
M. F. Faggin and D. B. Collum, J. Am. Chem. Soc., 2010, 132,
15610–15623.
14 A. H. Alberts and H. Wynberg, J. Am. Chem. Soc., 1989, 111,
7265–7266.
3
634–3636; (g) N. S. Simpkins and M. D. Weller, Top. Stereochem.,
010, 26, 1–52.
15 Very recently, the first catalytic enantioselective 1,2-addition of
alkynyllithiums onto ketones was published: K. Tanaka,
K. Kukita, T. Ichibakase, S. Kotani and M. Nakajima, Chem.
Commun., 2011, 47, 5614–5616.
2
E. Juaristi, A. K. Beck, J. Hansen, T. Matt, T. Mukhopadhyay,
M. Simson and D. Seebach, Synthesis, 1993, 1271–1290.
3
This journal is c The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 9915–9917 9917