The stereochemistry of allenic enol tautomerism - Independent generation and reactivity of the enolates

Article abstract of DOI:10.1002/ejoc.200600220

A priori, allenic enolates as reaction intermediates may be protonated to afford (Z)- or (E)-α,β-unsaturated carbonyl products. The allenic enolates are tautomeric with α-vinyl-carbanions. The literature on the behavior of these species on protonation is highly varied both in stereochemical outcome and in mechanistic interpretation. The current study has provided an independent mode of generation of the allenic enolates and has investigated the reaction stereochemistry of protonation to afford the stereoisomeric α,β-unsaturated carbonyl products. Under kinetic conditions, these highly reactive species are protonated in the α,β-π plane with preference (E) to the larger β group. Under thermodynamic conditions, addition/elimination equilibrates the two product stereoisomers. The kinetic protonation stereochemistry is a function of solvent, proton donor, and donor concentration. Computations serve to clarify the reaction mechanism. It was found that the stereochemistry of ketonization of allenic enolates follows the reaction course suggested as possible some decades earlier and common to less unique enolates. Additionally, the linear versus the bent enolate structure proves to depend on the countercation. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200600220

FULL PAPER
DOI: 10.1002/ejoc.200600220
The Stereochemistry of Allenic Enol Tautomerism – Independent Generation
and Reactivity of the Enolates[‡]
Howard E. Zimmerman*[a] and Alexei Pushechnikov[a]
Keywords: Stereochemistry / Kinetic protonation / Allenolates
A priori, allenic enolates as reaction intermediates may be
protonated to afford (Z)- or (E)-α,β-unsaturated carbonyl
products. The allenic enolates are tautomeric with α-vinyl-
carbanions. The literature on the behavior of these species
on protonation is highly varied both in stereochemical out-
come and in mechanistic interpretation. The current study
has provided an independent mode of generation of the all-
enic enolates and has investigated the reaction stereochemis-
try of protonation to afford the stereoisomeric α,β-unsatu-
rated carbonyl products. Under kinetic conditions, these
highly reactive species are protonated in the α,β-π plane with
preference (E) to the larger β group. Under thermodynamic
conditions, addition/elimination equilibrates the two product
stereoisomers. The kinetic protonation stereochemistry is a
function of solvent, proton donor, and donor concentration.
Computations serve to clarify the reaction mechanism. It was
found that the stereochemistry of ketonization of allenic enol-
ates follows the reaction course suggested as possible some
decades earlier and common to less unique enolates. Ad-
ditionally, the linear versus the bent enolate structure proves
to depend on the countercation.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Introduction
Our interest in the mechanism of protonation of meso-
meric anions began decades earlier.[2] One unique system
that had not received our experimental attention was the
behavior of allenic enols and enolates. Nevertheless, at the
time it was suggested that these are intermediates in the
Michael addition to acetylenic ketones and esters.[2] It was
noted that the allenic enolate species have two orthogonal
π systems, and it was proposed that under kinetic condi-
tions, the preferred protonation would be in the α,β plane,
which leads to the thermodynamically less stable α,β-unsat-
urated carbonyl product.
Scheme 1. Two alternative stereochemistries of kinetic protonation
of allenic enolates (L = larger group, S = smaller group).
Thus, our original 1955 suggestion[2] considered that the
transition state for protonation of the allenic enolate had
an α-carbon atom that should be close to sp-hybridized as
a result of the considerable exothermicity of the reaction.
The proposal further suggested that protonation would oc-
cur from the less-hindered face, having group S, with the
consequence that the higher-energy product would pre-
dominate (see Scheme 1).
Since that time a large amount of research has involved
reactions that must proceed either by way of the allenic
enolates or via their tautomeric vinyl carbanions in which
an α,β-enone has lost its α-hydrogen atom.
Background
In literature studies the stereochemical conclusions in the
case of the Michael addition to ethynylcarbonyl compounds
have been remarkably varied. The literature falls into two
categories: (a) the addition of anionic nucleophiles lacking
copper,[3] and (b) the addition of cuprates to the β-carbon
atom of the ethynyl system.[4]
In the basic reaction both vinyl carbanions and allenic
enolates have been considered as intermediates. In the
Michael addition to ethynyl esters and ethynyl ketones, var-
ied stereochemistries have been observed.[3a] The alkynones
were reported reasonably consistently to afford the (Z) ad-
ducts while the alkynyl esters largely afforded (E) adducts.
Nevertheless, product equilibration was noted to be a fac-
tor. In another investigation,[3b] the esters were reported to
lead to (Z) products while with acetamidomalonate as the
[‡] Part 280 of our General Papers. Part 279: Ref.[1]
[a] Department of Chemistry, University of Wisconsin – Madison,
Madison, Wisconsin 53706, USA
E-mail: zimmerman@chem.wisc.edu
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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nucleophile, Michael addition to tert-butyl propargylate, dence on the relative stability of the linear allenic enolate
the (E) stereoisomeric product was reported.[3c]
vs. the vinyl carbanion as a function of the counter cation.
Very early in the investigations of cuprate addition to
ethynyl systems were the pioneering studies by Corey,[4a]
Siddall,[4b] and Klein.[4c,4d] The Corey study assumed stereo-
specific formation of a vinylcopper intermediate at low
temperatures which isomerized to the (E) counterpart at
higher temperatures. Siddall considered two alternative re-
action intermediates, the vinylcopper and the copper allen-
olate, without a preference; however, at low temperature (Z)
addition was again observed. The most definitive mechan-
istic studies were by Klein who provided evidence for a
vinylcopper intermediate using infrared spectroscopy at low
temperatures. The formation and reaction of the vinylcop-
per species was shown to be stereospecific. But at higher
temperatures, the initial (Z)-vinylcopper species isomerized
to the (E) species. Additionally, Klein considered the copper
allenolate as the intermediate permitting the isomerization.
Interestingly, treatment of the vinylcopper species with
methyllithium led to a new species assumed to be the allen-
olate. This gave a varied stereochemistry which was ration-
alized utilizing our less-hindered protonation mechanism.[2]
Much more recently Krause[4e] utilized NMR analysis and
concluded that two copper allenolates are the species re-
sulting from Michael addition with the copper coordinating
differently but intramolecularly with the allenic system.
Subsequently, Ullenius and Krause[4f] have suggested that
both vinylcopper and copper allenolates are accessible de-
pending on the reagents used. It was suggested that proton-
ation of allenolates proceeded unselectively in the cases
studied. Finally, a theoretical study by Nakamura and
Morokuma has indicated that the vinylcopper species is of
lower energy than the allenolate which is involved only as
an intermediate permitting equilibration between (Z) and
(E) stereoisomers.[4g]
Results
Syntheses of Reactants
At the outset, it was the intention of the present research
to prepare an isolable precursor to a typical allenic enolate,
generate the enolate under controlled conditions, and deter-
mine the stereochemistry of the protonation reaction. For
this purpose the allenyl ether 4 was chosen.
A series of allenyl silyl ethers has been reported in an
elegant study by Reich[5] which made use of the Brook re-
arrangement.[6] Additionally, allenyl silyl ethers have been
obtained by a variety of approaches.[7]
Our synthesis, as outlined in Scheme 2, proved particu-
larly suitable for the system of interest. This began with
phenyl(phenylethynyl)methanol (1). On silylation with the
tert-butyldimethylsilyl chloride/imidazole combination, the
silyl ether 2 was obtained. With trial and error variation of
the reaction conditions, using n-butyllithium in hexane it
proved possible to generate anion 3. This anion was proton-
ated with imidazole to give the desired allenyl silyl ether 4.
During the imidazole protonation the lithium imidazole
salt precipitated and could readily be removed. The struc-
ture of allenyl silyl ether 4 was confirmed by H and 13C
1
NMR spectroscopy and its high-resolution mass spectrum.
Our general approach was inspired by reports[5,8] of anions
such as 3 reacting on silylation to afford allenyl silyl ethers.
However, those reported modes of generation and proton-
ation, applied to our anion 3, were unsuccessful.
Kinetic Protonation Studies
Hence, we were left with a rather confusing situation rel-
ative to the matter of protonation of allenolates. The pres-
Allenyl ether 4 proved stable at room temperature and
ent study primarily addresses the stereochemistry of the all- began to dimerize only after several days. The allenolate 5
enic enolate when it is clearly present. The relative stability was generated by an addition of a soluble fluoride salt to a
of the linear allenic enolate and the vinyl carbanion tauto- solution of the siloxyallene 4 and the corresponding proton
mer is also considered. Computational results provide evi- donor; see Scheme 3. In all cases these runs were monitored
Scheme 2. Synthesis of tert-butyldimethylsilyl ether 4.
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The Stereochemistry of Allenic Enol Tautomerism
FULL PAPER
vs. time to assure kinetic control of the stereoselectivity. The
results of the protonation with different donors, solvents
and concentrations are summarized in Tables 1, 2 and 3. It
is seen that there is a general preference for the formation
of the (Z) stereoisomer 7. The maximum stereoselectivity
observed was with diisopropylammonium as the proton do-
nor in dichloromethane. A plausible rationale is an increas-
ing intervention by aggregate donors, somewhat analogous
to the acetic acid effect noted in Table 3 and discussed be-
low.
The high stereoselectivity with diisopropylammonium as
the proton donor led us to consider the effect of its concen-
tration (Scheme 4). Table 2 summarizes our findings which
revealed that the stereoselectivity increased with the con-
centration of the amine hydrochloride. With 0.15  hydro-
Scheme 4. Preferred protonation (E) to the larger β substituent (L);
L is the larger and S is the smaller β substituent.
A particularly puzzling aspect of the literature reports
chloride the selectivity reached 85%. In the case of acetic was the variation in stereoselectivity encountered in the
acid as the proton donor, a similar increase in selectivity various studies involving Michael addition of nucleophiles
was encountered as the acetic acid concentration was in- to propargyl reactants. This led us to check the behavior of
creased. This reached 84% as noted in Table 3.
(Z)-chalcone in the presence of nucleophiles. The sodium
Scheme 3. Generation and kinetic protonation of 1,3-diphenylallenolate 5.
Table 1. Stereoselectivity with a variety of proton donors.
Proton source
(Z)/(E) ratio [normalized to (E) isomer]
THF (TBAF)
CH2Cl2 (TBAF)
MeOH (TBAF)
MeOH (KF)
iPrOH (TBAF)
None added
AcOH
PivOH
0.07
2.5
2.5
2.7
–
–
2.3
–
2.8
–
1.7
1.88
–
2.0
–
1.85
2.6
2.5
2.15
3.2
3.2
2.3
2.8
2.8
–
o-tBu-phenol[a]
Tetramethyl-piperidinium[b]
iPr2NH2Cl
[c]
–
[c]
–
4.2
2.7
2.7
[a] 2,6-Di-tert-butyl-4-methylphenol. [b] 2,2,6,6-Tetramethyl-4-propoxypiperidinium chloride. [c] Proton donor insufficiently soluble.
Table 2. Results of the protonation of allenolate 5 by diisopropylammonium chloride in iPrOH with increasing concentrations of the
proton donor.
Proton donor concentration []
Relative donor concentration
(Z)/(E) ratio [normalized to (E) isomer]
0.03
0.05
0.15
0.15
2
4
8
2.9
3.2
4.6
5.5
16
Table 3. Protonation of allenolate 5 in THF with increasing acetic acid concentrations.
Proton donor concentration []
Relative donor concentration
(Z)/(E) ratio [normalized to (E) isomer]
0.04
0.08
0.12
0.20
0.22
0.39
2
4
8
12
16
32
0.67
2.5
4.2
4.5
5.1
5.1
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H. E. Zimmerman, A. Pushechnikov
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conjugate base of diethyl malonate was typically used as the For the initial geometry optimizations RHF/3-21g* was
base in the Michael addition of diethyl malonate to ethynyl used, followed by density functional B3LYP/3-21g* and
phenyl ketones.
then B3LYP/6-31g*. Frequency computations revealed one
In the present study with 0.09  sodium malonate and imaginary eigenvalue for the transition structure (TS) ob-
(Z)-chalcone in ethanol at room temperature, an 80% (Z) tained. Our selection of computational methodology was
Ǟ (E) conversion resulted in 2 h. A similar isomerization based on practicality in order to give quantitatively mean-
was observed with diethylamine in diethyl ether. In 3 h at ingful but approximate results. Thus, the approach is ap-
room temperature a 1:1 (Z)/(E) mixture resulted and the proximate in not utilizing explicit solvent but simulation of
conversion approached 80% in 20 h [note Equation (1)].
a dielectric medium. In the QST3/B3LYP/6-31g* transition
state the hydrogen atom was found to be 1.086 Å from the
nitrogen atom and 1.865 Å from the allenic α-carbon atom.
Scheme 5 gives the density functional B3LYP/6-31g* ener-
gies obtained for the reaction. These, are “pseudo gas
phase” ones and too large for a solution process. They do,
however, illustrate semiquantitatively the reaction ener-
getics. Computational details are given in the Supporting
Information.
(1)
Discussion of Results and Conclusions
The first general conclusion is that on kinetic proton-
ation the typical allenic enolate studied does so by preferen-
tial attack from the less hindered side of the nearly linear
enolate moiety as suggested in our first publication on enol-
ate chemistry.[2] Thus, protonation occurs (E) to the large
β-phenyl group under most conditions. This then leads to
the thermodynamically less stable stereoisomer, namely (Z)-
chalcone (7).
Scheme 5. B3LYP computations (energies in parentheses are in
Hartrees).
Inspection of Table 1 reveals relatively little variation in
stereoselectivity with proton donors differing in steric bulk.
2,6-Di-tert-butyl-4-methylphenol does not show an en-
hanced selectivity compared with the smaller acetic and piv-
alic acid proton donors (note Table 1) in agreement with an
early transition state. Additionally, it is clear that there are
two modes of protonation – directly by the proton donor
utilized and indirectly by the solvent. At lower proton do-
nor concentrations the selectivity diminishes as solvent pro-
tonation becomes dominant (note, for example, Table 1).
With methanol as a solvent, the selectivity is low and one
may conclude that it is methanol which delivers the proton.
Table 3 also reveals another point of interest, namely the
increasing (Z)/(E) stereoselectivity as a function of increas-
ing acetic acid concentration in THF, a solvent which alone
cannot serve as a proton donor. This suggests that proton-
ation here is more than unimolecular, perhaps by the more
acidic acetic acid dimer. A similar effect has been seen in
our previous protonation studies (see ref.[1] and papers cited
therein).
Additionally, the geometries of the initial enolates as a
function of the counter cation were studied with the same
B3LYP/6-31G* methodology. Geometry optimization of
the enolates with sodium, lithium and copper as the counter
cations was carried out. In all the cases a high dielectric
medium was used to simulate solvent and the R groups
were simulated by hydrogen (see the Supporting Infor-
mation for computational details). The energies and angu-
larities are listed in Table 4. Interestingly, with sodium and
lithium as the counter cations, an essentially linear allenic
enolate was preferred (Table 4, Entries 2–4). In the lithium
case (Entry 4), the lithium–oxygen pair distance (1.72 Å)
was longer than expected for covalency. With sodium as the
counter cation (Entries 2 and 3), the geometry again was
linear and independent of the distance between the sodium
cation and the negative oxygen atom. But for lithium by
searching, there was found a local minimum of higher
energy and with a bent, vinyl structure (Entry 5). With cop-
per the (bent) vinyl carbanion structure resulted as a global
minimum on geometry optimization (Table 4, Entries 6 and
8). However, again, a local minimum of higher energy, now
Computational Aspects
A complementary computational approach seemed of with a linear structure was found computationally (En-
interest. In this, ammonia replaced an amine. Using QST2 tries 7 and 9).
and QST3 in the Gaussian03 group of programs,[9] the reac-
In comparing the lithium and copper equilibria of the
tion course depicted in Equation (2) resulted. The QST2 global minima with the higher energy local minima, it is
method required prior geometry optimizations of the reac- seen that the preferred linear lithium species is lower in en-
tant R (an ammonium enolate) and the product P (chalcone ergy than the vinyl one by 7.5 kcal/mol [Equation (3)] while,
plus an ammonia molecule). This was followed by the se- in contrast, the vinylcopper minimum is lower in energy
arch for the reaction transition state (TS). Once a transition than the linear counterpart by 13.8 kcal/mol [note Equa-
state was obtained, this was used for a QST3 computation. tion (4)].
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The Stereochemistry of Allenic Enol Tautomerism
FULL PAPER
Table 4. Computational results on linearity vs. environment.
Entry
Enolate
Angle 2–3–4 [°]
M–O bond length [Å]
Energy [Hartrees]
Comments
1
2
3
4
5
6
7
8
9
gas phase
Na
137.764
179.593
179.467
179.137
115.806
121.165
178.521
116.736
179.382
n. a.
2.09
4.12
1.72
1.24
1.89
1.178
1.87
1.08
–461.67390
–624.02296
–624.02299
–469.27035
–469.25869
–2103.14748
–2103.11993
–2110.16989
–2110.14836
no cation, minimum
Na–O not fixed, minimum
Na–O fixed at 4.12 Å, minimum
global minimum
Na
Li
Li
Cu
local minimum
single copper
local minimum
global minimum
CuR2
CuRLi(1)
CuRLi(2)
local minimum
Thus, much of the literature discrepancies now become form covalent bonds to the α-carbon atom and the prefer-
understandable. The copper species, indeed, is a vinyl spe- ence for a high electron density at the oxygen atom. The
cies with a nonlinear enone structure as originally proposed result is the formation of the linear allenic enolate studied
by Klein. However, a local minimum of linear structure and experimentally in this investigation.
higher energy was found computationally (note Entries 6
and 8). We can surmise that this linear copper enolate is
the intermediate permitting (Z)- and (E)-vinyl carbanions
to equilibrate at higher temperatures.
Conclusions
The role of the cation is seen to be considerable. With no
It is seen that the original 1955 speculation,[2] and that
cation or solvent present, the preferred gas-phase species is of some subsequent literature (vide supra), of allenic enols
the (bent) vinyl carbanion (note Entry 1 in Table 4). The with their two orthogonal π systems protonating to give
general preference of linearity with the lithium and sodium the less stable of two α,β-unsaturated carbonyl products is
counter cations may be ascribed to the inability of these to confirmed experimentally and computationally. However,
Eur. J. Org. Chem. 2006, 3491–3497
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General Procedure for Kinetic Protonation of 1-(tert-Butyldimethyl-
siloxy)-1,3-diphenylpropa-1,2-diene (4) with Acetic Acid in THF To
Afford Chalcone Isomers 6 and 7: To a stirred solution of siloxyal-
lene 4 (0.20 g, 0.64 mol) in10 mL of THF 1.3 mL of a 2.0  THF
solution of glacial acetic acid was added followed by 1.3 mL of a
1.0  THF solution of tetrabutylammonium fluoride. The reaction
mixture was stirred at room temperature and samples of the reac-
tion solution were taken to monitor the process by HPLC. After
2 h of stirring, the reaction mixture was partitioned between water
(100 mL) and hexane (30 mL), the organic phase dried with magne-
sium sulfate and concentrated in vacuo at room temperature. The
residual mixture contained (Z)- and (E)-chalcone in a ratio of 2.4:1
as measured by 1H NMR analysis; the corresponding characteristic
peaks of (Z)- and (E)-chalcone were identified by comparison with
pure isomers. After column separation (SiO2//hexane/dichloro-
methane, 4:1) three major fractions were collected. (a): 5.0 mg of a
monosilated dimer of the reactant allene 8. 1H NMR (300 MHz,
CDCl3): δ = –0.19 (s, 3 H), 0.48 (s, 3 H), 0.79 (s, 9 H), 4.76 (dd, J
= 9.6, J = 2.7 Hz, 1 H), 4.87 (d, J = 9.6 Hz, 1 H), 6.39 (d, J =
2.1 Hz, 1 H), 6.79 (m, 2 H), 7.02 (m, 3 H), 7.09 (m, 3 H), 7.16–
7.26 (m, 5 H), 7.4 (dq, J = 8.4 Hz, 2 H), 7.55 (tt, J = 7.8 Hz, 2 H),
7.64 (tt, J = 7.2 Hz, 1 H), 8.12 (dt, J = 7.2 Hz, 2 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = –3.8, –1.3, 18.5, 26.1, 49.3, 52.9, 86.1,
126.3, 127.1, 127.2, 127.4, 127.6, 127.9, 128.1, 128.4, 128.9, 129.2,
129.6, 133.5, 134.9, 137.4, 138.0, 141.3, 143.8, 195.9 ppm. EI-
HRMS: calcd. for C32H29O2Si· 473.1937 [M–tBu]·+, found
473.1923. (b): (Z)-Chalcone 7, 49 mg. 1H NMR (300 MHz,
CDCl3): δ = 6.62 (d, J = 12.9 Hz, 1 H), 7.02 (d, J = 12.9 Hz, 1 H),
7.20–7.26 (m, 3 H), 7.37–7.43 (m, 4 H), 7.52 (tt, J = 7.2, J = 1.4 Hz,
1 H), 7.97 (dm, J = 7.2 Hz, 2 H) ppm. (c): (E)-Chalcone 6, 22 mg.
1H NMR (300 MHz, CDCl3): δ = 7.39–7.44 (m, 3 H), 7.47–7.68
(m, 6 H), 7.82 (J = 15.6 Hz, 1 H), 8.03 (dm, J = 7.0 Hz, 2 H) ppm.
This gives a (Z)/(E) ratio of 2.23:1, slightly different from the one
measured by NMR spectroscopy, apparently due to isomerization
on silica gel.
the preference for the linear allenolate extends only for po-
lar media and with alkali metal cations. In contrast, ab ini-
tio computations find a preference for the vinyl carbanion
geometry along with a higher energy local minimum with
linearity in the absence of solvent and in the case of copper.
Experimental Section
General Procedures: Nuclear magnetic resonance spectra (1H and
13C, 300 MHz and 75 MHz, respectively) were obtained in CDCl3
with TMS as an internal standard. Isomer ratios were determined
1
by H NMR spectral integrals. These were collected with a relax-
ation delay of 17.0 s. Melting points were determined in open capil-
laries and a heating block. Column chromatography (CC) was per-
formed on a column slurry-packed with 60–200 mesh silica gel. All
solvents were freshly distilled from appropriate drying agents under
nitrogen before use.
Synthesis of 1,3-Diphenylprop-2-yn-1-ol (1): The method employed
by Spee et al.[10] afforded a yield of 9.7 g (91%), b.p. 127–129 °C/
1
1 Torr. H NMR (300 MHz, CDCl3): δ = 2.61 (d, J = 6.25 Hz, 1
H), 5.67 (d, J = 6.25 Hz, 1 H), 7.22–7.49 (m, 8 H), 7.56 (m, 2 H)
ppm.
Synthesis of 1-(tert-Butyldimethylsiloxy)-1,3-diphenylprop-2-yne (2):
To a stirred solution of 1,3-diphenylprop-2-yn-1-ol (1, 3.5 g,
16.8 mmol) and imidazole (1.3 g, 18.5 mmol) in 30 mL of dichloro-
methane a solution of tBuMe2SiCl (2.8 g, 18.5 mmol) in 20 mL of
dichloromethane was added at once. The reaction mixture was
stirred at room temp. for 24 h. Then the solution was washed with
water and with aqueous Na2CO3 (10%). The organic phase was
dried with sodium sulfate and concentrated in vacuo. The residue
was flash-filtered with hexane through a short silica gel column.
Concentration in vacuo afforded the product as a colorless oil,
which became yellow after exposure to air and light. Yield 5.34 g
General Procedure for Kinetic Protonation of 1-(tert-Butyldimethyl-
siloxy)-1,3-diphenylpropa-1,2-diene (4) with Varying Solvents and
1
(98%). H NMR (300 MHz, CDCl3): δ = 0.23 (s, 3 H), 0.26 (s, 3
H), 0.99 (s, 9 H), 5.77 (s, 1 H), 7.3–7.47 (m, 8 H), 7.58–7.62 (m, 2
H) ppm. 13C NMR (75 MHz, CDCl3): δ = –4.8, –4.3, 18.4, 25.9,
65.3, 85.7, 90.1, 126.2, 127.7, 128.2, 128.3, 131.6, 141.7 ppm. EI-
HRMS: calcd. for C17H17OSi· 265.1049 [M–tBu]·+, found
265.1047.
Proton Donors: To
a stirred solution of allene 4 (0.050 g,
0.16 mmol) in 10 mL of the selected solvent (THF, MeOH,
CH2Cl2, or iPrOH) a calculated amount of a studied proton donor
was added followed by crystalline tetrabutylammonium fluoride
(0.11 g, 0.32 mmol). The reaction mixture was stirred at room tem-
perature for 2 h. Then the reaction mixture was partitioned be-
tween water (100 mL) and hexane (30 mL), the organic phase was
dried with magnesium sulfate and concentrated in vacuo at room
temperature. The ratio of (Z)/(E) isomers in the residual mixture
Proton Transfer in 1-(tert-Butyldimethylsiloxy)-1,3-diphenylprop-2-
yne (2) to Afford 1-(tert-Butyldimethylsiloxy)-1,3-diphenylpropa-1,2-
diene (4): To a stirred solution of 1-(tert-butyldimethylsiloxy)-1,3-
diphenylprop-2-yne (2, 1.0 g, 3.1 mmol) in hexane/THF (10 mL/
5 mL) a solution of nBuLi (1.53 mL, 2.48  in hexane) at –78 °C
was slowly added. The mixture turned dark red. The reaction mix-
ture was stirred at –78 °C for 30 min and then a solution of imid-
azole (0.26 g, 3.8 mmol) in THF (5.0 mL) was added in one portion
to the vigorously stirred solution at –78 °C. The color changed to
pale orange and a lithium imidazole salt precipitated. After further
stirring at –78 °C for 20 min, the solution was diluted with 30 mL
of dry hexane and stirred until room temp. was reached, followed
by filtration and concentration in vacuo of the filtrate. The residue
was partitioned between 25 mL of dry acetonitrile and 75 mL of
hexane. The hexane layer was filtered and concentrated in vacuo
1
was determined by H NMR analysis.
General Procedure for Kinetic Protonation of 1-(tert-Butyldimethyl-
siloxy)-1,3-diphenylpropa-1,2-diene (4) in Methanol with KF: To a
stirred solution of allene 4 (50 mg, 0.16 mmol) in 10 mL of MeOH
a calculated amount of the selected proton donor was added fol-
lowed by 0.32 mL of a 1.0  MeOH solution of potassium fluoride.
The solution was stirred at room temperature for 2 h. Then the
reaction mixture was partitioned between water (100 mL) and hex-
ane (30 mL), the organic phase was dried with magnesium sulfate
and concentrated in vacuo at room temperature. The ratio of (Z)/
(E) isomers in the residual mixture was measured by 1H NMR
analysis.
1
to give the product as a yellow oil; yield 0.87 g (87%). H NMR
(300 MHz, CDCl3): δ = 0.14 (s, 3 H), 0.20 (s, 3 H), 1.0 (s, 9 H),
6.95 (s, 1 H), 7.22–7.42 (m, 8 H), 7.54–7.57 (m, 2 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = –4.7, –4.5, 18.5, 26.1, 107.6, 125.2,
127.8, 128.0, 128.4, 128.9, 134.6, 135.3, 200.6 ppm. EI-HRMS:
calcd. for C21H26OSi 322.1753 [M]·+, found 322.1756.
Preparation of an Analytical Sample of (Z)-Chalcone (7) by UV
Irradiation of (E)-Chalcone (6): After irradiating a solution of (E)-
chalcone (6, 25 g) in acetonitrile (250 mL) with a 100-W mercury
lamp with circulated 0.2  aqueous CuSO4 as a UV filter for 12 h,
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Eur. J. Org. Chem. 2006, 3491–3497

The Stereochemistry of Allenic Enol Tautomerism
FULL PAPER
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a mixture (1:1) of the isomers was obtained. The solvent was re-
moved and the residual yellow oil was separated in portions. The
(Z)/(E) mixture (5.0 g) was chromatographed on an activated car-
bon (Barnebey-Cheney) column (25 mm×400 mm). Following elu-
tion with 500 mL of hexane, the (Z) isomer was eluted with 300 mL
of benzene. After the first 50 mL of eluent, 2.1 g of essentially pure
(Z)-chalcone (7) was eluted as a yellow oil. The oil was recrys-
tallized from methanol at –25 °C to give 1.6 g of yellow crystals of
(Z)-chalcone (7), m.p. 44–45 °C.
Susceptibility of (Z)-Chalcone (7) to Epimerization with Dieth-
ylamine: To
a stirred solution of (Z)-chalcone (7, 0.10 g,
0.48 mmol) in 5.0 mL of diethyl ether 0.050 mL of diethylamine
was added. The mixture was stirred at room temp. for 40 min and
an aliquot was concentrated in vacuo and the residue analyzed by
1H NMR spectroscopy. The mixture consisted of (Z)- and (E)-chal-
cone in a ratio of 1.4:1. No traces of signals of an amine adduct
were detected. After 3 h of reaction, the (Z)/(E) ratio was 1:1. After
20 h, the (Z)/(E) ratio was 0.17:1. After 44 h, the (Z)/(E) ratio was
less than 0.03:1.
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Epimerization of (Z)-Chalcone (7) by Sodium Diethyl Malonate: To
a stirred solution of diethyl malonate (0.015 g, 0. 09 mmol) in abso-
lute ethanol (5 mL) sodium hydride (0.004 g, 0.1 mmol, 60% dis-
persion in mineral oil) was added. The mixture was stirred for
5 min and (Z)-chalcone (7, 0.1 g, 0.48 mmol) was added. The mix-
ture was stirred at room temp. for 2 h and the first sample was
analyzed. The sample was concentrated in vacuo to dryness at
room temp. and the residue was analyzed by 1H NMR spec-
troscopy. The mixture consisted of (Z)-/(E)-chalcone in a ratio of
0.17:1 along with a corresponding amount of the Michael reaction
product.
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra and computational deatils.
Acknowledgments
Support of this research by the National Science Foundation is
gratefully acknowledged with special appreciation for its support
of basic research.
[1] a) H. E. Zimmerman, J. Cheng, J. Org. Chem. 2006, 71, 873–
882; b) see also H. E. Zimmerman, A. Pushechnikov, Org. Lett.
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Received: March 13, 2006
[2] H. E. Zimmerman, J. Org. Chem. 1955, 20, 549–557.
Published Online: May 30, 2006
Eur. J. Org. Chem. 2006, 3491–3497
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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