1,3-Li/H shift of 1-Aryl-1,2-alkadienyl reagents: An experimental and theoretical study

Article abstract of DOI:10.1002/chem.200801849

A mechanism involving the exchange of equilibrated protons initiated by a catalytic amount of a proton donor, the most effective of which appears to be di-isopropylamine was proposed. The thermodynamic potential of the rearrangement was first examined com

Full text of DOI:10.1002/chem.200801849

COMMUNICATION
DOI: 10.1002/chem.200801849
1,3-Li/H Shift of 1-Aryl-1,2-alkadienyl Reagents: An Experimental and
Theoretical Study
Nacira Alouane,[a] Kamel Bentayeb,[a] Emmanuel Vrancken,*[b] Hꢀlꢁne Gꢀrard,*[c] and
Pierre Mangeney*[a]
The possibility of a metallotropic equilibrium in organo-
lithium compounds derived from propargylic compounds
complicates the structural determination[1] and potential re-
action products of these reagents. Their versatility is of great
interest, especially for the lithiated 1-aryl-1-alkynes 1 for
which an additional rearrangement (Scheme 1) has been ob-
have reported this transposition to be highly non-reproduci-
ble, the only experimentally reproducible conditions are the
use of lithium diisopropylamine (LDA) as a base at room
temperature.[4a,b] We faced this troublesome non-reproduci-
bility during the course of our experimental studies on allen-
yl metals[6] with 1-phenyl-1-butyne 1a (Scheme 1) in non-
LDA conditions. In line with our theoretical examinations
of organolithium compound structures,[7] we decided to elu-
cidate the origin and mechanism of this shift to master its
versatility.
The thermodynamic potential of the rearrangement was
first examined computationally, since reversion of the stabil-
ity of the two isomers (1-Li vs. 2-Li, Scheme 1) as a function
of chelation or solvation is the more straightforward explan-
ation for the non-reproducibility. The energetics of the 1,3-
shift was thus studied by comparing the relative stabilities of
1a-Li and 2a-Li allenic species (Scheme 1), which are sug-
gested to be preferred to the propargylic one from experi-
mental data.[1] Allenic species 2a-Li was found to be the
most stable isomer, when considering either an uncoordinat-
ed anion (3.1 kcalmolÀ1), or for lithiated species with a
naked Li (3.5 kcalmolÀ1), for solvated systems (continuum:
2.0 kcalmolÀ1; three discrete OMe2: 2.9 kcalmolÀ1), or even
for Li coordinated to ethylenediamine (6.4 kcalmolÀ1).
These computational results were supported by the fol-
lowing experimental findings: treatment of 3 (afforded from
hydrolysis of 1a-Li) by sBuLi followed by deuteration coun-
ter-intuitively yields only deuteration at the methylated po-
sition to give a mixture of 4a and 4b in a 1/0.7 ratio
(Scheme 2). Similar regioselectivities were previously re-
ported for the deprotonation of phenylallene or 3 by
nBuli.[4d,5]
Scheme 1.
served.[2] Despite its discovery by Klein 40 years ago[2,3] and
its clever applications to allene synthesis,[4] the mechanism
of this reaction is still unclear. Pathways involving either
1,3-H or 1,3-Li/H shifts have been implicated by Klein and
Maercker,[2,3,5] without systematic confirmation. Ma et al.
[a] Dr. N. Alouane, K. Bentayeb, Dr. P. Mangeney
Laboratoire de Chimie Organique, UMR CNRS 7611
Institut de Chimie Molꢀculaire, FR 2769
case 43, 4 Place Jussieu 75262 Paris Cedex 05 (France)
[b] Dr. E. Vrancken
Institut Charles Gerhardt Montpellier
ENSCM, 8, rue de l’ꢀcole Normale, 34296 Montpellier (France)
Fax : (+33)4-67-14-43-22
E-mail: emmanuel.vrancken@enscm.fr
[c] Dr. H. Gꢀrard
Laboratoire de Chimie Thꢀorique, UMR 7616
UPMC - Univ. Paris 06, CNRS
case 137, 4 Place Jussieu 75262 Paris Cedex 05 (France)
Scheme 2.
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45

The greater stability of 2À or 2-Li with respect to the 1À
analogues strongly suggests that the 1,3-shift should be ob-
served under all conditions and that its non-reproducibility
has to be linked to kinetic factors. To determine the exact
role of lithium within this shift, the reaction was experimen-
tally undertaken in the presence and absence of Li chelators
(hexamethylphosphoramide (HMPA) and tetramethyl-1,2-
ethanediamine (TMEDA)). Lithiation of 1a by sBuLi was
initially carried out at À808C. The reaction mixture was
then slowly allowed to reach room temperature and transpo-
sition was monitored by deuteration of aliquots sampled at
increasing temperature. Rearrangement occurs under three
conditions: at 08C in the absence of chelator, at À208C in
the presence of TMEDA, and at À408C with HMPA. Re-
producibility remained poor in all cases. These results could
indicate a mechanism that involves separated ion pairs, the
rearrangement taking place in an anionic species free of
counter-ion coordination.
volving a dimeric aggregate
transfer from one entity to the other, via a dilithiated inter-
mediate ACTHNURTGENNG(U 7-Li)2 was envisioned. When the mechanism of the
ACHTUNGERTN(NUNG 1a-Li)2 (Scheme 3). Hydrogen
Scheme 3.
non-substituted lithiated (with two OMe2 on each Li) system
is considered, the corresponding dilithiated intermediate is
located 18.6 kcalmolÀ1 above the reactant, and the activa-
tion energy for this reaction is 26.1 kcalmolÀ1. These values
remain much too high to be consistent with a reaction
taking place within a few minutes at 08C.
An intramolecular 1,3-shift within such an anion was thus
theoretically examined. Despite our attempts, no direct shift
could be found, and a two-step pathway was determined,
which involved transposition of the H from C1 to C2 in a
As reproducible conditions involve the use of LDA as a
base, a possible mixed aggregate between LDA and 1a-Li
has been envisioned, because such species sometimes exhibit
modified basicity with respect to the separated partners.[8]
This hypothesis was experimentally revoked since no trans-
position occurred when a stoichiometric amount of LDA
was added to the pre-formed 1a-Li and the reaction was al-
lowed to reach room temperature. This last experiment indi-
cates that the role of LDA as a deprotonating agent that
allows transposition has to be sought within its conjugate
acid, formed after deprotonation of 1a, and not in the LDA
reactant itself. This was verified by adding a catalytic
amount of diisopropylamine to the pre-formed 1a-Li. Under
these conditions, transposition occurs cleanly at À208C. The
role of the secondary amine as the key reagent to allow
transposition was checked by the following reaction se-
quence, which thereafter was used as a standard protocol: i)
sBuLi was added to the propargyl 1a to pre-form 1a-Li at
À808C; ii) the reaction mixture was warmed up to room
temperature (RT); iii) the absence of 2a-Li was checked by
deuteration of an aliquot; iv) the reaction mixture was
cooled down to À808C and a catalytic amount (5 mol%) of
diisopropylamine was added; v) the reaction mixture was
warmed to À208C where the rearrangement began and then
allowed to reach room temperature. A total rearrangement
was observed after one hour at 208C. The following reaction
sequence is proposed as a mechanism for the transposition:
1a-Li (obtained from 1a by deprotonation either by using
an organolithium reagent or by using LDA) reacts with the
diisopropylamine (respectively introduced as a catalyst or
formed as the conjugate base) to form the allene and LDA
(Scheme 4). Deprotonation can then take place on the most
first step through transition state (TS) TS
ACHTUNGTRENNUNG
6À, and then a second migration through TS
AHCTUNGTRENNUNG
C2 to C3 (Figure 1). This mechanism is found to be utterly
Figure 1. Electronic energies (E) and sum of electronic and thermal free
energies (G) in kcalmolÀ1 for intramolecular 1,3-shift.
unrealistic since the intermediate 6À is about 60 kcalmolÀ1
above that of the reactant and the activation energy is
larger than 70 kcalmolÀ1! Attempts at stabilizing intermedi-
ate 6À by using another conformational arrangement of the
Me and Ph groups have failed, as the conformational iso-
mers of 6À found are all more than 55 kcalmolÀ1 above 1À.
Coordination of the anion to Li+ does not lead to much
lower barriers, as 6-Li was found to be 52.6 kcalmolÀ1 above
1a-Li, and the two TS were 65.8 and 70.2 kcalmolÀ1 above
1a-Li, respectively. Similar results were obtained when the
mechanism for a fully unsubstituted model was studied (re-
action intermediate 59.1 kcalmolÀ1 above the reactant, and
activation energy equal to 80.3 kcalmolÀ1), which will be
used for further mechanistic studies.
Thus, no intramolecular transposition could be found the-
oretically and we turned our attention to a mechanism in-
Scheme 4.
46
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Chem. Eur. J. 2009, 15, 45 – 48

1,3-Li/H Shift of 1-Aryl-1,2-alkadienyl Reagents
COMMUNICATION
favorable site, on the methylated carbon, resulting in the
formation of 2a-Li.
Experimental Section
Diisopropylamine-mediated 1,3-Li shift: A freshly titrated solution of
sBuLi (2.2 mmol, 1.1 equiv) was slowly added to a solution of 1-phenyl-1-
butyne (0.284 mL, 2 mmol) in THF (15 mL) at À808C under argon. The
temperature of the mixture was allowed to reach À408C in one hour and
the reaction mixture was cooled to À808C. Diisopropylamine [0.042 mL,
0.3 mmol (excess of sBuLi + 5% of 1-phenyl-1-butyne)] was then added,
and the temperature of the mixture was slowly allowed to reach room
temperature. The 1,3-Li shift was monitored by 1H NMR analyses of ali-
quots obtained after the deuteration reaction, under anhydrous condi-
tions, with MeOD and found to be complete after one hour at room tem-
perature.
Ma and co-workers recently reported deuterium-labeling
experiments of 1-deuterated-1-phenylocta-1,2-diene. A loss
of D was observed when LDA was used, whereas a total re-
tention was seen with nBuLi, which was attributed by the
authors to isotopic effects.[4d] Nevertheless, according to the
difference of pKa of the two metallation sites of the allene,
such a result can be fully explained by a mechanism based
on equilibrated proton exchange between bases and conju-
gate acids, which is impossible with the use of nBuLi under
anhydrous conditions. Such a reaction sequence can only be
performed if LDA and 1-Li have pKa values of the same
order. Thus to replace diisopropylamine as the catalytic
proton transfer agent requires the participation of an acid
whose conjugate base is of similar strength to that of 1a-Li.
The obvious choice was to add the allene 3 in catalytic
amounts (Scheme 5) under the standard experimental proto-
Computational Methods
Full geometry optimizations were systematically conducted with no sym-
metry restraints using the Gaussian 03 program[10] within the framework
of density functional theory (DFT) using the hybrid B3LYP exchange-
correlation functional[11] and the 6–31+G** basis set for all atoms. Im-
plicit solvation was added when mentioned using the PCM model, and
the dielectric constant was implemented for THF (eR =7.58).[12] Frequen-
cies were evaluated within the harmonic approximation. The nature of
the transition states was ensured by confirming the presence of a single
imaginary frequency. The connection between transition states and
minima was ensured by carrying out small displacements of all atoms in
the two directions along the imaginary frequency mode and carrying out
geometry optimization using these geometries as starting points.
Scheme 5.
col. The rearrangement, which started at À208C, afforded a
mixture of 2a-Li and 1a-Li in a 3/1 ratio after one hour at
208C. Theoretically, proton exchange between 3 and the
monomeric disolvated 1a-Li exhibits an activation energy of
17.3 kcalmolÀ1, which is fully consistent with the experimen-
tal conditions. Similar experimental results were obtained by
using a catalytic amount of 1a. In this case, the transposition
was found to be slower (1/1 ratio after 1 h at 208C).
In conclusion, based on our experimental and theoretical
studies, we propose a mechanism involving the exchange of
equilibrated protons initiated by a catalytic amount of a
proton donor, the most effective of which appears to be di-
Acknowledgements
The authors thank CCR (Univ. Paris VI, Paris, France), CINES (Mont-
pellier, France), IDRIS (Orsay, France), and CRIHAN (Rouen, France)
for computing facilities, and Clariant and the programme franco-algꢀrien
de formation supꢀrieure for financial support.
Keywords: allenes · allenyl lithium · density functional
calculations · reaction mechanisms
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Received: September 8, 2008
Published online: November 26, 2008
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Chem. Eur. J. 2009, 15, 45 – 48