Stereochemistry of the tetrabutylammonium cyanide-catalyzed cyanosylilation of cyclic α,β-epoxyketones - Dependence of the diastereoselectivity on the ring size

Article abstract of DOI:10.1002/ejoc.200600239

The diastereoselective Bu₄NCN-catalyzed addition of TMSCN to cyclic α,β-epoxyketones has been considered. Good diastereoselectivities were found, depending on the ring size of the starting material. Computational studies account for the observed diastereoselectivities. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200600239

FULL PAPER
DOI: 10.1002/ejoc.200600239
Stereochemistry of the Tetrabutylammonium Cyanide-Catalyzed
Cyanosylilation of Cyclic α,β-Epoxyketones – Dependence of the
Diastereoselectivity on the Ring Size
Ana Aljarilla,[a] Rubén Córdoba,[a] Aurelio G. Csaky,[a] Israel Fernández,[a][‡]
Fernando López Ortiz,[b] Joaquín Plumet,*[a] and Gloria Ruiz Gómez[b]
Dedicated to the memory of Prof. Marcial Moreno Mañas
Keywords: Ab initio calculations / Diastereoselectivity / Cyanohydrins / Epoxyketones / Trimethylsilyl cyanide / Tetrabu-
tylammonium cyanide
The diastereoselective Bu4NCN-catalyzed addition of
TMSCN to cyclic α,β-epoxyketones has been considered.
Good diastereoselectivities were found, depending on the
ring size of the starting material. Computational studies ac-
count for the observed diastereoselectivities.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
able from safety standpoints.[5] With few exceptions,[6] this
reagent is only effective in the transfer of the CN group to
the carbonyl moiety of aldehydes or ketones under the ac-
tion of activators, which are mainly organometallic Lewis
acids.[1] However, from the point of view of their environ-
mentally benign nature, their ease of handling, and the cost
of the reaction process, metal-free organocatalysts have re-
cently attracted the attention of organic chemists. In this
context, the use of different organocatalysts for the cyanosi-
lylation of aldehydes and ketones has been reported.[7] Re-
cently, we communicated the use of phosphonium[8] and
ammonium[9] salts as a convenient catalytic reagent for the
cyanosilylation of aldehydes and ketones. In this report, we
wish to account for the application of tetrabutylammonium
cyanide as the catalytic agent for the diastereoselective cya-
nosilylation of α,β-epoxyketones. As a matter of fact, an
unprecedented dependence of the diastereoselectivity on the
ring size in the case of cyclic epoxyketones has been ob-
served. This behavior may be explained through appropri-
ate theoretical calculations.
Introduction
Cyanohydrins constitute versatile starting materials use-
ful as intermediates for the synthesis of a variety of relevant
targets such as α-hydroxyacids, β-amino alcohols, and their
derivatives.[1] In particular, ketone cyanohydrins are of spe-
cial interest as starting materials for the preparation of
compounds with stereogenic quaternary centers.[2] The vari-
ety of synthetically useful transformations of the cyanohyd-
rin moiety combined with those of other reactive functional
groups in close proximity may give rise to new chemistry
with no analogy in monofunctional systems. Considering
that epoxides are important reactive intermediates,[3] we
have envisaged the combination of an epoxide and a ketone
cyanohydrin in the same molecule, focusing our attention
on α,β-epoxycyanohydrins derived from α,β-epoxyketones.
To the best of our knowledge, the stereocontrolled synthesis
of these types of compounds has not been considered in
previous literature.[4]
Among the various reagents available for the cyanosi-
lylation of ketones,[2] the use of TMSCN has proven valu-
[a] Universidad Complutense, Facultad de Química, De-
partamento de Química Orgánica, Ciudad Universitaria,
28040 Madrid, Spain
Results and Discussion
E-mail: plumety@quim.ucm.es
[b] Universidad de Almería, Área de Química Orgánica, Carretera
de Sacramento,
For the synthesis of α,β-epoxy-O-TMS cyanohydrins,
two different strategies can be envisioned (Scheme 1): epox-
idation of the cyanohydrins of α,β-unsaturated ketones
(strategy a) or cyanohydrin formation from α,β-epoxy-
ketones (strategy b).
04120 Almería, Spain
[‡] Author to whom the questions related to the computational
calculations should be addressed.
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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The inspection of these data puts forward that, for the
epoxyketones 2–6, good diastereoselectivities were obtained
in all cases (Table 1, entries 1–5). However, the diastereo-
selectivity (i.e. the prevalence of isomer a or b) depended
on the ring size of the starting cyclic epoxyketone. Thus,
while the five-membered compounds 2 and 6 (Table 1, en-
tries 1 and 5) afforded cyanohydrins a (arising from the
anti-oxirane attack of the nucleophile on the carbonyl
group) as major diastereomers, the six-, seven-, and eight-
membered compounds 3, 4, and 5 (Table 1, entries 2, 3, and
4) afforded cyanohydrins b (arising from the syn-oxirane
attack of the nucleophile on the carbonyl group) as major
diastereomers.
Scheme 1.
The configurational assignment[11] was based on 1D
1
gNOESY spectra. The H NMR spectra of compounds 7–
At first, strategy a looks more appealing, because strat-
egy b may suffer from competitive ring opening of the oxir-
ane moiety under these reaction conditions.
Therefore, at the onset of our study, we considered the
Bu4NCN-catalyzed addition of TMSCN to ketone 1b with
subsequent epoxidation (mCPBA, CH2Cl2, Scheme 2) by
using strategy a. The reaction took place only with low
yield (10%, 2 h, room temperature), and diastereomers 8a
and 8b were obtained in a 1:1 ratio.
11 consisted of a series of complex multiplets, except for the
methine protons of the oxirane ring and the methyl protons
of the TMS group. The methylene protons adjacent to the
CH group could be identified through 1D gCOSY and 1D
gTOCSY experiments. Stereochemical assignments were
mainly based on the observations of NOE effects between
the methine protons of the oxirane moiety and the methyl
protons of the TMS group in the b isomers (Table 1 and
Figure 1).
Discouraged by both low diastereoselectivity and
yield,[10] we switched over to strategy b and considered the
The stereochemical outcome of the reaction (i.e. the de-
Bu4NCN-catalyzed addition of TMSCN to the α,β-epoxy- pendence of the diastereomeric ratio on the ring size of the
ketone 3 (Scheme 3), obtained in turn by the epoxidation starting material) is an intriguing question. In order to get
of the related α,β-unsaturated ketone 1b. We observed that, more insight into the factors responsible for the observed
in this case, diastereomers 8a and 8b were obtained in a 1:3 diastereoselectivity, computations were carried out on the
ratio and 90% isolated yield.
cyclic systems 2–6. Under kinetic control (see Table 2),[12]
In light of this result, we undertook the study of the the observed diastereoselectivity may be explained in terms
Bu4NCN-catalyzed addition of TMSCN to the cyclic α,β- of free activation energy differences (∆∆G‡298) of the syn or
epoxyketones 2–6. The results of these reactions are gath- anti addition of the nucleophile to the corresponding ep-
ered in Table 1.
oxyketone. The picture of the reaction path for this cata-
Scheme 2.
Scheme 3.
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Diastereoselectivity of Cyclic α,β-Epoxyketone Cyanosylilation Depends on Ring Size
Table 1. Bu4NCN-catalyzed cyanosilylation of epoxyketones 2–6.
FULL PAPER
1
[a] Diastereomeric ratios were determined by the integration of the corresponding signals in the H NMR spectra (CDCl3, 300 MHz) of
the crude reaction mixtures. [b] Yield of the pure compound, isolated as a diastereomeric mixture.
Table 2. Relative energies [∆E][a] of the syn and anti isomers of com-
pounds 7–10.
Figure 1. Representation of the NOE effects observed only in the
b isomers.
lyzed addition is not a simple matter. The catalytic role of
the ammonium salt may be explained by assuming a hyper-
valent silicon intermediate, thus increasing the efficiency of
the cyanide ion transfer.[13] There is no doubt that, by anal-
ogy with many other reactions involving activated silicon
species,[14] the mechanism of the process should involve an
initial and a reversible attack of the nucleophilic catalyst to
give a pentacoordinate silicon intermediate (Scheme 4). The have been calculated at the B3LYP/6-31++G**+∆ZPVE level.
[a] ∆E values in kcal/mol, computed as ∆E = Eanti – Esyn. All values
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question is whether this first intermediate behaves as a
source of “naked” reactive cyanide ion or undergoes coor-
dination with the carbonyl group of the epoxyketone to give
a hexacoordinate intermediate (or transition state), which
evolves to the products by intramolecular transfer of the
cyanide ion.[15] In these cases, however, all attempts to lo-
calize the transition state derived from a pentacoordinate
silicon nucleophilic attack on an epoxyketone to give a
hexacoordinate silicon intermediate met with no success.
Thus, at least in these cases, the stereochemical result arises
from the nucleophilic attack of an activated cyanide nucleo-
phile on the carbonyl group. The intermediacy of this
“hard” nucleophile can also explain the regioselectivity (i.e.
attack only on the carbonyl group) of the reaction of some
Figure 2. Ball and stick representations of transition states for the
nucleophilic addition of the cyanide ion to compounds 2–5. All
structures correspond to fully optimized B3LYP/6-31++G(d,p) ge-
ometries. Bond lengths are given in Å and angles in degrees. Unless
otherwise stated, white (small), white (big), gray, and black colors
denote hydrogen, carbon, oxygen, and nitrogen atoms, respectively.
Scheme 4.
Scheme 5.
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Diastereoselectivity of Cyclic α,β-Epoxyketone Cyanosylilation Depends on Ring Size
FULL PAPER
spiroepoxycyclohexadienones with TMSCN in the presence ized orbital to the σ*3,5 orbital and from the σ3,4 orbital to
of Bu4NCN.[9b,16] σ*2,6 orbital. We found the highest values of the stabilizing
Thus, the observed diastereoselectivity may be explained perturbation energy [∆E(2)] in the TS-2syn and TS-6syn
in terms of free activation energy differences (∆∆G‡298) of transition states (7.1 kcal/mol and 3.7 kcal/mol, respec-
the syn or anti addition of the cyanide ion (which is rapidly tively, for TS-6syn and 6.9 kcal/mol and 3.4 kcal/mol,
formed from the hypervalent silicon species) to the corre- respectively, for TS-2syn). These large stabilizing energies
sponding epoxyketones (Scheme 5).
override the steric interactions associated with these transi-
As readily seen in Figure 2, in the reactive approximation tion states. On the other hand, in the transition states de-
the nucleophile follows a typical nonperpendicular Bürgi–
Dunitz trajectory[17] with angles ca. 110–111º and
Table 3. Calculated ∆∆G‡298 (syn–anti) vaules for cyanide addition
NϵC···C(=O) distances ranging from 1.9–2.2 Å. In general,
to epoxyketones 2–6.
the latter geometrical feature is always shorter in the syn
transition states than that in the corresponding anti ana-
logues.
The calculated ∆∆G‡298 values measured as ∆G‡298(TS-
syn) – ∆G‡298(TS-anti) are compiled in Table 3. It is clear
that for small ring sizes (i.e. five-membered epoxyketone 2
and its aromatic analogue 6), the free activation energies of
the syn addition are smaller. In sharp contrast, the corre-
sponding transition states for the anti addition in six- to
eight-membered epoxyketones 3–5 are more stable than the
syn attack transition states, and therefore, the reactions in-
volving compounds 3–5 lead to anti products predomi-
nantly. In consequence, the diastereoselectivity of this pro-
cess strongly depends on the ring size. These results are in
good agreement with the experimental findings.
The stereochemical outcome of the process may be ex-
plained in terms of Felkin–Anh’s model,[18] which means
that cyanide addition takes place preferentially from the less
hindered side of the carbonyl group to afford the observed
anti isomer for epoxyketones 3–5. However, the epoxy-
ketones 2 and 6 (five-membered ring compounds) do not
follow this trend based on steric considerations. Thus, elec-
tronic factors should play an important role in these cases,
and the stereochemical result must be the consequence of a
delicate balance between both contributions.[19] Second-or-
der perturbation theory reveals the origins of this stereo-
[a] Relative free activation energy difference [∆∆G‡298 (syn–anti)]
control. In both transition states TS-2syn and TS-6syn
(Figure 3), there are two two-electron donations that stabi-
lize both species, and therefore, render the syn addition
more favorable than the anti addition. As readily seen in
values in kcal/mol computed as ∆∆G‡298 = ∆G‡298(syn) – ∆G‡298(anti).
All values have been calculated at the B3LYP/6-31++G(d,p) level.
[b] Experimental diastereomeric ratio determined by integration of
1
the appropriate signals in the H NMR (CDCl3, 250 MHz) spectra
Figure 3, the electronic donations occur from the σ1,2 local- of the crude reaction mixtures.
Figure 3. Two-electron interactions and associated second-order perturbation energies, ∆E(2), in transition state TS-6syn.
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J. Plumet et al.
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bond orbitals having ʦφ and ʦφ*energies, respectively; nφ stands
for the occupation number of the filled orbital.
rived from epoxyketones 3–5, the stabilization associated
with these two-electron donations is much smaller than the
corresponding ∆E(2) values for the TS-2syn and TS-6syn
transition states. For instance, the ∆E(2) values for TS-5syn
are 3.9 kcal/mol and 0.7 kcal/mol, respectively. Therefore,
compounds 3–5 follow the general trend and produce the
anti isomer.
Cyanosilylation of Epoxyketones
Starting Materials: The experimental procedures for the synthesis
of starting epoxyketones 2–6 obtained by epoxidation reactions of
the related α,β-unsaturated ketones 1a–e are described in the Sup-
porting Information.
General Procedure: To a solution of the epoxyketone (100 mg,
1.02 mmol) in dry CH2Cl2 (5 mL) was added, under argon and at
room temperature, TMSCN (0.25 mL, 2.04 mmol) followed by a
solution of Bu4NCN (27 mg, 0.10 mmol) in dry CH2Cl2 (5 mL).
The mixture was stirred at room temperature for 1 h. The solvent
was evaporated under vacuum. The crude reaction mixture was di-
luted with Et2O (10 mL) and washed with H2O (2×10 mL). Drying
of the organic phase with MgSO4 was followed by evaporation of
the solvent under vacuum. The product was purified by chromatog-
raphy on silica gel (ethyl acetate/hexane, 1:5).
Conclusions
In conclusion, we have described the chemo- and dia-
stereoselective formation of cyanohydrins derived from cy-
clic α,β-epoxyketones using TMSCN as the cyanide source
and Bu4NCN as the catalyst. Under these reactions condi-
tions, good diastereoselectivities were obtained. In the case
of the cyanohydrins derived from five-membered cyclic ep-
oxyketones, the reaction leads mainly to the syn dia-
stereomer arising from the anti-epoxide attack of the in-
coming nucleophile, whereas in the case of cyanohydrins
derived from six-, seven-, and eight-membered cyclic
ketones, the anti diastereoisomer (syn nucleophilic attack
with respect to the epoxide moiety) was the major one.
These results may be explained by considering the stereoe-
lectronic effects associated with both competitive transition
states, which can be accurately reproduced by computa-
tional experiments.
2-[(Trimethylsilyl)oxy]-6-oxabicyclo[3.1.0]hexane-2-carbonitrile (7):
Colorless oil (195 mg, 0.99 mmol). Yield: 98%. Diastereomeric
1
mixture (7a/7b = 4:1). 7a: H NMR (CDCl3, 500 MHz): δ = 0.29
(s, 9 H), 1.75 (dd, J = 11.7, 8.5 Hz, 1 H), 1.83 (dd, J = 11.7, 9.0 Hz,
1 H), 2.12 (dd, J = 13.3, 9.0 Hz, 1 H), 2.21 (dd, J = 13.3, 8.5 Hz,
1 H), 3.56 (d, J = 2.6 Hz, 1 H), 3.66 (d, J = 2.6 Hz, 1 H) ppm. 13C
NMR (CDCl3, 50 MHz): δ = 24.91, 32.62, 55.17, 59.64, 74.91,
119.61 ppm. MS (70 eV): m/z (%) = 182 (49) [M – CH3]+, 155 (34)
[M – CH3 – HCN]+, 127 (81), 84 (28), 81 (33), 75 (55) [(CH3)2-
SiOH]+, 73 (100) [(CH3)3Si]+, 45 (44), 43 (22), 41 (75). 7b: 1H NMR
([D6]DMSO, 500 MHz): δ = 0.22 (s, 9 H), 1.50–2.10 (m, 4 H), 3.73
(d, J = 2.5 Hz, 1 H), 3.82 (d, J = 2.5 Hz, 1 H). MS (70 eV): m/z
(%) = 182 (21) [M – CH3]+, 155 (69) [M – CH3 – HCN]+, 126 (12),
113 (14), 101 (13), 84 (16), 81 (35), 75 (28) [(CH3)2SiOH]+, 73 (100)
[(CH3)3Si]+, 47 (13), 45 (35), 43 (16). C9H15NO2Si (197.31): calcd.
C 54.79, H 7.66, N 7.10; found C 54.95, H 7.80, N 7.00.
It should be pointed out that, from the synthetic point
of view, the combination of functional groups present in
these molecules may promote their use as building blocks
for the synthesis of more complicated scaffolds.
2-[(Trimethylsilyl)oxy]-7-oxabicyclo[4.1.0]heptane-2-carbonitrile (8):
Experimental Section
Orange oil (255 mg, 1.21 mmol). Yield: 90%. Diastereomeric mix-
1
ture (8a/8b = 1:3). 8a: H NMR (CDCl3, 500 MHz): δ = 0.32 (s, 9
Computational Details: All the calculations reported in this paper
were obtained with the GAUSSIAN 03 suite of programs.[20] Elec-
tron correlation has been partially taken into account by using the
hybrid functional usually denoted as B3LYP,[21] and the standard
6-31++G(d,p) basis set[22] was selected in order to obtain accurate
energies. Zero point vibrational energy (ZPVE) corrections have
been computed at the B3LYP/6-31++G(d,p) level and have not
been corrected. Stationary points were characterized by frequency
calculations[23] and have positive defined Hessian matrices. Transi-
tion structures (TSs) show only one negative eigenvalue in their
diagonalized force constant matrices, and their associated eigenvec-
tors were confirmed to correspond to the motion along the reaction
coordinate under consideration by using the Intrinsic Reaction Co-
ordinate (IRC)[24] method. Donor–acceptor interactions have been
computed with the Natural Bond Order (NBO)[25] method. The
energies associated with these two-electron interactions have been
computed according to the following Equation (1):
H), 1.40–2.10 (m, 6 H), 3.20 (d, J = 3.5 Hz, 1 H), 3.34 (t, J =
3.5 Hz, 1 H) ppm. 8b: H NMR (CDCl3, 500 MHz): δ = 0.30 (s, 9
H), 1.40–2.10 (m, 6 H), 3.38 (t, J = 4.0 Hz, 1 H), 3.40 (d, J =
4.0 Hz, 1 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 18.82, 21.16,
32.03, 55.09, 56.71, 70.65, 119.72 ppm. C10H17NO2Si (211.33):
calcd. C 56.83, H 8.11, N 6.63; found C 56.60, H 8.20, N 6.41.
1
2-[(Trimethylsilyl)oxy]-8-oxabicyclo[5.1.0]octane-2-carbonitrile (9):
Colorless oil (40 mg, 0.20 mmol). Yield: 85%. Diastereomeric mix-
1
ture (9a/9b = 1:8). 9a: H NMR (CDCl3, 300 MHz): δ = 0.28 (s, 9
H), 1.30–2.20 (m, 8 H), 3.14–3.24 (m, 1 H), 3.35 (d, J = 4.4 Hz, 1
H) ppm. MS (70 eV): m/z (%) = 210 (27) [M – CH3]+, 183 (66)
[M – CH3 – HCN]+, 180 (42), 181 (6), 168 (31), 155 (29), 154(24),
129 (23), 92 (27), 84 (23), 81 (46), 75 (100) [(CH3)2SiOH]+, 73 (76)
[(CH3)3Si]+, 67 (22), 55 (21). 9b: 1H NMR (CDCl3, 300 MHz): δ =
0.30 (s, 9 H), 1.30–1.70 (m, 4 H), 1.80–2.00 (m, 2 H, CH2), 2.02–
2.20(m, 2 H), 3.18 (m, 1 H), 3.27 (d, J = 4.4 Hz, 1 H) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 23.20, 23.53, 28.11, 38.94, 56.90,
61.16, 73.69, 121.26 ppm. MS (70 eV): m/z (%) = 210 (6) [M –
CH3]+, 184 (7), 183 (53) [M – CH3 – HCN]+, 182 (8), 181 (6), 174
(9), 173 (18), 172 (100), 168 (6), 155 (9), 129 (9), 109 (6), 81 (20),
75 (5) [(CH3)2SiOH]+, 73 (8) [(CH3)3Si]+, 67 (6). C11H19NO2Si
(225.36): calcd. C 58.63, H 8.50, N 6.22; found C 58.47, H 8.29, N
6.31.
(1)
where Fblabla is the density functional theory (DFT) equivalent of
the Fock operator and φ and φء are two filled and unfilled natural
2-[(Trimethylsilyl)oxy]-9-oxabicyclo[6.1.0]nonane-2-carbonitrile
(10): Yellow oil (40 mg, 0.29 mmol). Yield: 98%. Diastereomeric
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Diastereoselectivity of Cyclic α,β-Epoxyketone Cyanosylilation Depends on Ring Size
FULL PAPER
1
[6]
[7]
For instance: a) D. A. Evans, L. K. Truesdale, G. L. Caroll, J.
Chem. Soc. Chem. Commun. 1973, 55; b) K. Manju, S. Trehan,
J. Chem. Soc. Perkin Trans. 1 1995, 2383.
mixture (10a/10b = 1:19). 10b: H NMR (CDCl3, 300 MHz): δ =
0.29 (s, 9 H), 1.20–1.76 (m, 6 H), 1.80–2.15 (m, 5 H), 2.27(ddd, J
= 14.6, 6.8, 2.2 Hz, 1 H), 2.87 (dt, J = 10.7, 4.2 Hz, 1 H), 3.27 (d,
J = 4.2 Hz, 1 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 19.79,
23.36, 24.59, 26.08, 41.61, 56.77, 58.65, 70.10, 122.06 ppm. MS
(70 eV): m/z (%) = 224 (18) [M – CH3]+, 206 (22), 197 (52) [M –
CH3 – HCN]+, 172 (41), 129 (26), 105 (27), 95 (100), 75 (32)
[(CH3)2SiOH]+, 73 (38) [(CH3)3Si]+, 55 (17). 10a: 1H NMR
(CDCl3, 300 MHz): δ = 0.30 (s, 9 H), 1.20–2.35 (m, 10 H), 2.92–
2.97 (m, 2 H) ppm. MS (70 eV): m/z (%) = 224 (43) [M – CH3]+,
197 (96) [M – CH3 – HCN]+, 169 (29), 155 (30), 154 (36), 129 (48),
95 (74), 84 (29), 75 (85) [(CH3)2SiOH]+, 73 (100) [(CH3)3Si]+, 55
(31). C12H21NO2Si (239.39): calcd. C 60.21, H 8.84, N 5.85; found
C 60.34, H 9.09, N 5.76.
See ref.[1] and among others: a) P. Saravanan, R. V. Anand,
V. K. Singh, Tetrahedron Lett. 1998, 39, 3823; b) R. Somana-
than, I. A. Rivero, A. Gama, A. Ochoa, G. Aguirre, Synth.
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Chem. 2000, 2, 47; f) Z. G. Wang, B. Fetterly, J. G. Verkade, J.
Organomet. Chem. 2002, 646, 16; g) J. S. Yadav, M. S. Reddy,
A. R. Prasad, Tetrahedron Lett. 2002, 43, 9703; h) N. Azizi,
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Lundgren, S. Lutsenko, C. Jonsson, C. Moberg, Org. Lett.
2003, 5, 3663; j) C. Baleizao, B. Grigante, H. Garna, A. Corma,
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2004, 92, 123; l) H. Zhou, F. X. Chen, B. Quin, X. Feng, G.
Zhang, Synlett 2004, 1077; m) L. Yan, H. Bin, F. Xiaoming,
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6-[Trimethylsilyloxy]-6,6a-dihydro-1aH-indene[1,2-b]oxirene-6-car-
bonitrile (11): Colorless oil (21 mg, 0.14 mmol). Yield: 80%. Dia-
stereomeric mixture (11a/11b = 3:1). 11a: 1H NMR (CDCl3,
300 MHz): δ = 0.27 (s, 9 H), 4.23 (d, J = 2,6 Hz, 1 H), 4.32 (d, J
= 2.6 Hz, 1 H), 7.32–7.62 (m, 4 H) ppm. 13C NMR (CDCl3,
50 MHz): δ = 56.91, 57.65, 74.17, 118.66, 125.58, 126.03, 129.80,
130.27, 138.24, 141.81 ppm. MS (70 eV): m/z (%) = 245 (18) [M+·],
230 (100) [M – CH3]+, 217 (48), 203 (47) [M – CH3 – HCN]+, 202
(28), 186 (27), 156 (27), 118 (47), 90 (27), 89 (31), 75 (24) [(CH3)2-
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Calculations of the relative stabilities of compounds 7–11 rule
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SiOH]+, 73 (95) [(CH3)3Si]+. 11b: H NMR (CDCl3, 300 MHz): δ
1
[10]
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[12]
= 0.17 (s, 9 H), 4.24 (d, J = 2.4 Hz, 1 H), 4.39 (d, J = 2.4 Hz, 1
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230 (89) [M – CH3]+, 203 (33) [M – CH3 – HCN]+, 202 (28), 186
(83), 156 (41), 146 (26), 118 (100), 101 (25), 90 (28), 89 (35), 84 (24),
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Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures for the synthesis of the starting ep-
oxyketones, stereochemical assignments of new compounds, and
Cartesian coordinates (in Å) and free energies (in a.u.) of all transi-
tion states discussed in the text.
[15]
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Acknowledgments
Ministerio de Educación, Cultura y Deporte, Project BQU2003-
04967 is gratefully thanked for financial support.
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3969–3976