Remote stereocontrol mediated by the sulfinyl group: Hydrocyanation of 2-p-tolylsulfinyl benzaldehyde

Article abstract of DOI:10.1016/j.tetasy.2005.04.031

Enantiomerically pure cyanohydrins derived from 2-p-tolylsulfinyl benzaldehyde can be obtained by reaction with different hydrocyanating reagents in the presence of Yb(OTf)₃ or Y(OTf)₃.

Full text of DOI:10.1016/j.tetasy.2005.04.031

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1963–1968
Remote stereocontrol mediated by the sulfinyl group:
hydrocyanation of 2-p-tolylsulfinyl benzaldehyde
*
Jose Luis Garcıa Ruano, Ana M. Martın-Castro, Francisco Tato and Diego J. Cardenas
*
´
´
´
´
´ ´ ´
Departamento de Quımica Organica, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
Received 7 March 2005; accepted 27 April 2005
Abstract—Enantiomerically pure cyanohydrins derived from 2-p-tolylsulfinyl benzaldehyde can be obtained by reaction with differ-
ent hydrocyanating reagents in the presence of Yb(OTf)3 or Y(OTf)3.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
ral auxiliary. In this field, from the excellent results ob-
tained in reactions of 2-p-tolylsulfinyl substituted benzyl
carbanions with different electrophiles,9 it can be in-
ferred that the sulfinyl group is also efficient at control-
ling the stereoselectivity at nucleophilic centers
separated by three bonds from the stereogenic sulfur
(1,4-asymmetric induction). Other research groups have
proven that this efficiency can also be maintained for
electrophilic centers located at similar positions. Thus,
Solladie et al. reported the stereoselective reduction of
c-ketosulfoxides10 and Toru and co-workers published
noteworthy results concerning the reactions of 2-formyl-
1-sulfinylnaphthalenes with Grignard reagents.11 How-
ever, when the latter reactions were studied on 2-sulfinyl-
benzaldehydes, the stereocontrol was not efficient unless
2,4,6-triisopropylphenyl sulfoxides were used as the chi-
ral auxiliaries,12 which decreased the synthetic interest of
these reactions due to the drawbacks derived from the
non-trivial preparation of the starting materials. Despite
the poor results obtained by Toru from 2-p-tolylsulfinyl
benzaldehyde, we decided to explore its behavior of such
a chiral auxiliary in the hydrocyanation reactions of this
substrate, because these nucleophilic additions on b-
ketosulfoxides13 had exhibited better stereoselectivity
control than the corresponding alkylation reactions.
Regardless of the obtained results, our goal was quat-
ernization of the benzyl carbon at the resulting cyanohy-
drins by taking advantage of the ability shown by the
ortho-sulfinyl group in controlling the stereoselectivity
at such a carbon.9 Thus, we report herein the results
of the reaction of (S)-2-p-tolylsulfinylbenzaldehyde 1
with different hydrocyanating reagents and propose a
reasonable stereochemical model supported by theoreti-
cal calculations (Scheme 1).
As has been extensively documented, enantiomerically
pure cyanohydrins are attractive building blocks as syn-
thetic intermediates in the preparation of a-hydroxy
acids,1 which are frequently involved in the synthesis
of peptides, a-hydroxy ketones,2 a-halonitriles,3 and a
number of natural products.4 As a consequence, much
effort has been focused on their asymmetric synthesis.5
However, the successful results achieved in reactions
with aldehydes5 contrast with the much lower number
of efficient methods to obtain cyanohydrins derived
from ketones.6 This suggests that the search for methods
allowing the stereocontrolled quaternization of the
hydroxylic carbon at the cyanohydrins derived from
aldehydes could be a new strategy to obtain cyanohy-
drins derived from ketones and therefore would signifi-
cantly widen the access to these compounds.
Over the last few decades, the sulfinyl group has been
extensively used as a chiral auxiliary due to its high ver-
satility, as well as its easy incorporation into organic
substrates and its ready removal from the target mole-
cules. Several years ago, our research group reported
the efficiency of the sulfinyl group to control the stereo-
selectivity of different nucleophilic additions to b-keto-
sulfoxides.7 In particular, excellent results were obtained
in their hydrocyanation reactions with Et2AlCN, giving
rise to diastereomerically pure sulfinylcyanohydrins.8
More recently we initiated a program focused on the
evaluation of the sulfinyl groupÕs ability as a remote chi-
*
Corresponding authors. E-mail: joseluis.garcia.ruano@uam.es
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.04.031

´
J. L. Garcıa Ruano et al. / Tetrahedron: Asymmetry 16 (2005) 1963–1968
1964
O
NC
O
O
S
OH
H
HO
O
CN
H
S
CN-
Et2AlCN
H
Tol
H
Tol
H
+
Solvent
T (ºC)
S
S
S
NC OH
O
O
Tol
Tol
Tol
O
4b
1
4a
Scheme 1.
Scheme 3.
2. Results and discussion
Enantiomerically pure (S)-2-p-tolylsulfinylbenzaldehyde
1 was prepared in high overall yield over a two-step
sequence starting from commercially available 2-bromo-
benzaldehyde diethyl acetal. Sulfinylation and subse-
quent hydrolysis of the acetal function of 3 afforded
our target molecule 1 (Scheme 2).14
tions. However, none of these changes was synthetically
significant.
Next we considered the influence of different Lewis acids
on the course of the reaction. The hydrocyanation did
not work in the presence of some of them [Sc(OTf)3,
Sn(OTf)2]. However, the results were highly satisfactory
in the presence of Yb(OTf)3 (entries 11–13) and Y(OTf)3
(entry 14), yielding 4a as the major or exclusive (at
ꢀ78 ꢁC) diastereoisomer.
Initially we studied the reactions of compound 1 with
Et2AlCN under different conditions (solvent, tempera-
ture, addition mode—direct or inverse, amount of re-
agent, see Scheme 3).
Configurational assignment for 4a was unequivocally
established by chemical correlation with the commer-
cially available (R)-mandelamide 5 (Kowa Fine Chemi-
cals). Such a correlation was performed by hydrolysis of
the cyano group at 4a followed by desulfinylation of the
crude mixture without further purification (Scheme 4). It
is noteworthy that the hydrolysis took place under very
mild conditions (HBF4/NaI at rt), contrasting with the
usually strong conditions required to transform nitriles
into amides,15 and evolved with simultaneous reduction
of the sulfinyl into a sulfenyl group. It suggests that the
reaction proceeds with anchimeric assistance of the sul-
finyl group, as demonstrated in other sulfinyl nitriles.16
Significant results concerning yields and diastereomeric
ratios are indicated in Table 1. In the absence of Lewis
acids, reactions in THF both at ꢀ20 ꢁC and ꢀ78 ꢁC pro-
vided diastereomeric mixtures of cyanohydrins 4a and b
with low deÕs. The composition of these mixtures re-
mained unaltered with the reaction times, which exerted
only little influence on the conversion degree (entries 1–
4). Similar results were obtained in CH2Cl2 (entries 5
and 6). When toluene was used as the solvent some
changes in the composition of the reaction mixtures
were observed (entries 7–10), which suggests that an
equilibrium between 4a and b occurs under these condi-
OEt
OEt
OEt
O
PyOTs
1) BuLi, -78 °C
OEt
H
Acetone/H2O
2) (S)-TolS(O)-OMent
S
Br
S
2
3
Tol
1
O
O
Tol
Scheme 2.
Table 1. Reaction of 1 with Et2AlCN under different conditions (Scheme 3)
Entry
Solvent
T (ꢁC)
Time
Lewis acid
Conversion (%)
Ratio 4a:4ba (Yield, %)
1
THF
THF
ꢀ20
ꢀ20
ꢀ78
ꢀ78
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ78
ꢀ78
1 min
2 h
—
—
100
100
83
70:30
70:30
56:44
2
3
THF
THF
5 min
2 h
—
—
4
100
75
56:44
50:50
5
CH2Cl2
CH2Cl2
Toluene
Toluene
Toluene
Toluene
THF
5 min
2 h
—
—
6
100
60
50:50
35:65
7
5 min
15 min
30 min
2 h
—
—
8
60
50
26:74
62:38
9
—
—
10
11
12
13
14
20
75
65:35
75:25
5 min
30 min
2 h
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Y(OTf)3
THF
THF
THF
100
100
100
75:25
>98(92):<2
96(82):4
2 h
a Determined by integration of well-separated signals in the 1H NMR spectra of the crude mixture.

´
J. L. Garcıa Ruano et al. / Tetrahedron: Asymmetry 16 (2005) 1963–1968
OH OH
CN CONH2
1965
O
1) Yb(OTf)3, THF
2) Et2AlCN
1) HBF4, NaI
H
2) Ra-Ni, EtOH
S(O)Tol
S(O)Tol
5
1
4a
de > 98%
chemical correlation
Ra-Ni, EtOH
HBF4, NaI
OH
OH
NH
CONH2
STol
O
S
Tol
I
Scheme 4.
The almost complete stereoselectivity observed for reac-
tions conducted under Yb(OTf)3 or Y(OTf)3 catalysis
suggests that the metal must be able to form a stable se-
ven-membered chelated species with both the sulfinyl
and carbonyl oxygens, which have only one face acces-
sible to attack by the hydrocyanating reagent. In the ab-
sence of the catalyst, Et2AlCN apparently is unable to
form similar seven-membered chelates, despite it being
efficient in forming six-membered ones with b-keto-
sulfoxides.8 As a consequence, the association of the
aluminum only to the sulfinyl oxygen followed by a
barely stereoselective intramolecular transfer of the cya-
nide to the carbonyl group would account for the low
observed stereoselectivity in the absence of Yb(OTf)3
or Y(OTf)3.
silyl cyanides in the presence of Yb(OTf)3 in order to ob-
tain protected and, therefore, more stable, silylated
cyanohydrins. The reactions with TMSCN and
In order to support this stereochemical proposal we
performed DFT calculations on yttrium complexes A
derived from Y(OTf)3. Since the reactions performed
well in CH2Cl2, which is a non-coordinating solvent,
the model complexes included the bidentate organic
ligand along with three bidentate triflates, to give
coordination number eight. Several starting geometries
differing in the conformation of the seven member
chelate were fully optimized using the B3LYP hybrid
functional. The optimized complexes show a distorted
square anti-prism arrangement around Y. The carbonyl
and the sulfoxide ligands can occupy two coordination
sites corresponding either to the same or different faces
of the anti-prism. The most stable complexes show the
chelate within the same face. For this type of geometry,
several arrangements of the triflate ions were conside-
red. The resulting complexes lie within a range of
0.7 kcal molꢀ1, and show a very similar conformation
for the seven member ring. The carbonyl group is copla-
nar with the aromatic ring, and exhibits a very different
steric hindrance for both faces (see Figs. 1–3). The
nucleophilic attack on the less hindered face is fully con-
sistent with the observed stereoselectivity. When the
sulfoxide and the carbonyl join different faces of the
anti-prism, less stable complexes (ca. 5 kcal molꢀ1) are
obtained, although they support the same stereochemi-
cal outcome.
Figure 1.
Figure 2.
According to this model, the stereoselectivity is only
dependent on the catalyst and therefore the role of the
hydrocyanating reagent must be irrelevant. In this sense,
we performed the hydrocyanation with different trialkyl-
Figure 3.

´
J. L. Garcıa Ruano et al. / Tetrahedron: Asymmetry 16 (2005) 1963–1968
1966
OTMS
CN
TMSCN, CH2Cl2
TBAF, AcOH
THF
Yb(OTf)3, -20 ºC, 1 d
OH
CN
S(O)Tol
6 (95%), de>98%
S(O)Tol
4a
OTBDMS
CN
O
TBDMSCN, CH2Cl2
TBAF, AcOH
THF
TBAF,
AcOH
H
Yb(OTf)3, 0 ºC, 4 d
S(O)Tol
S(O)Tol
THF
OTiPS
1
7 (92%), de=96%
CN
OTiPS
S(O)Tol
CN
chromatographic
separation
8a
TiPSCN, CH2Cl2
Yb(OTf)3, rt, 5 d
OH
CN
OTiPS
CN
S(O)Tol
TBAF,
AcOH
8 (95%), de=40%
THF
S(O)Tol
4b
S(O)Tol
8b
Scheme 5.
TBDMSCN proceeded at low temperatures affording
the O-silylated cyanohydrins 6 and 7, respectively, in
high yields with excellent levels of diastereoselectivity
(Scheme 5). These results are particularly interesting in
the case of exploiting of the so obtained enantiomeri-
cally pure cyanohydrins as chiral synthons for further
synthetic transformations, which frequently use O-pro-
tected derivatives as starting materials. Conversely, reac-
tions with TIPSCN17 did not evolve completely
stereoselectively due to the higher temperature required
to reach completion (Scheme 5).
brid functional.19 The standard 3-21G basis set was used
for C, H, O, F, and S, while the LANL2DZ relativistic
pseudopotential was used for Y. Harmonic frequencies
were calculated at the same level of theory to character-
ize the stationary points and to determine the zero-point
energies (ZPE).20
4.2. General methods
NMR spectra were obtained in a Bruker spectrometer
(300 and 75 MHz for 1H and 13C, respectively) in CDCl3
solutions. Melting points were measured using a Gal-
lemkamp apparatus in open capillary tubes. Mass spec-
tra (MS) were determined at FAB+. Specific rotations
were measured in a Perkin–Elmer 241 MC polarimeter.
All reactions were carried out in anhydrous solvents and
under an argon atmosphere. THF and Et2O were dis-
tilled from sodium-benzophenone under argon. CH2Cl2
was distilled from P2O5. Flash column chromatography
was performed using silica gel Merk-60 (230–400 mesh).
Enantiomeric excesses were determined by HPLC using
a column CHIRALPAK AD as a chiral stationary
phase. Aldehyde 1,3 acetal 33 and TIPSCN17 were pre-
pared following previously reported procedures.
Diastereomerically pure O-silylated cyanohydrins 6 and
7 can be readily correlated with 4b (thus confirming their
configurational assignment) by treatment with TBAF/
AcOH (Scheme 4). This correlation reinforces our
hypothesis, which postulates the scarce role of the
hydrocyanating reagent on the stereochemical course
of these reactions catalyzed by Yb(OTf)3.
3. Conclusions
From the above results we can conclude that the hydro-
cyanation of (S)-2-p-tolylsulfinylbenzaldehyde with
Et2AlCN and R3SiCN is highly stereoselective in the
presence of some Lewis acids such as Yb(OTf)3 or
Y(OTf)3 as a consequence of the cyanide attack on a che-
late involving aldehyde and sulfoxide coordination with
the metal, as proven by the calculation at a DFT level.
4.3. General procedure for hydrocyanation
4.3.1. With Et2AlCN. A solution of 244.3 mg (1 mmol)
of (S)-2-(p-tolylsulfinyl)benzaldehyde 1 in 5 mL of THF
was added dropwise into
a solution of 2.5 mL
(2.5 mmol) of Et2AlCN 1 M in toluene diluted in
10 mL of THF at ꢀ78 ꢁC. The mixture was stirred at
ꢀ78 ꢁC for 2 h. The reaction mixture was transferred
by cannula (by applying a positive argon pressure to
the reaction flask) into a mixture of 2.5 mL of methanol
and 2.5 mL of concentrated HCl, cooled at ꢀ78 ꢁC. The
resulting mixture was vigorously stirred at ꢀ78 ꢁC for
1 h, poured into a mixture of 1.5 mL of concentrated
HCl and 1.5 mL of ice-water, and extracted with
4. Experimental
4.1. Computational methods
The calculations were performed with the GAUSSIAN
98 series of programs.18 The geometries of all complexes
were optimized at the DFT level using the B3LYP hy-

´
J. L. Garcıa Ruano et al. / Tetrahedron: Asymmetry 16 (2005) 1963–1968
1967
CH2Cl2 (3 · 5 mL). The extracts were washed with
water (10 mL), dried over Na2SO4, and the solvent evap-
orated at a reduced pressure.
4.7. (2R,(S)S)-2-[2-(p-Tolylsulfinyl)phenyl]-2-(trimethyl-
silyloxy)acetonitrile 6
The reaction was stirred at ꢀ20 ꢁC for 24 h and the pro-
4.3.2. With Et2AlCN/X(OTf)3 (X = Yb, Y). A solution
of 244.3 mg (1 mmol) of (S)-2-(p-tolylsulfinyl)benzalde-
hyde 1 and 1 mmol of Yb(OTf)3 or Y(OTf)3 in 5 mL
of THF was stirred for 30 min at room temperature
and then added dropwise into a solution of 2.5 mL
(2.5 mmol) of Et2AlCN 1 M in toluene diluted in
10 mL of THF at ꢀ78 ꢁC. The resulting mixture was
vigorously stirred at ꢀ78 ꢁC for 1 h and then worked
up as in method A.
tected cyanohydrin purified by flash column chromato-
graphy (AcOEt–hexane 1:3). Yield: 95%; white solid;
20
D
mp: 142–143.2 ꢁC; ½aꢁ = ꢀ67.8 (c 1, CHCl3); IR
(KBr): 2401, 1215, 756 cmꢀ1
;
1H NMR: d 7.88–7.85
(m, 1H), 7.82–7.79 (m, 1H), 7.62–7.58 (m, 2H), 7.48
and 7.30 (AA0BB0 system, 4H), 6.21 (s, 1H), 2.40 (s,
3H), 0.23 (s, 9H); 13C NMR: d 142.9, 141.6, 141.2,
135.2, 131.9, 130.5, 130.0, 128.4, 127.2, 125.4, 118.0,
59.5, 21.1, ꢀ0.3.
4.4. (2R,(S)S)-2-Hydroxy-2-[2-(p-tolylsulfinyl)phen-
yl]acetonitrile 4a
4.8. (2R,(S)S)-2-(tert-Butyldimethylsilyloxy)-2-[2-(p-tol-
ylsulfinyl)phenyl]acetonitrile 7
The product was purified by crystallization from hex-
ane–ethyl ether. Yield: 92%; mp: 134–136 ꢁC; white
The reaction was stirred at 0 ꢁC for 4 days and the pro-
tected cyanohydrin was isolated by flash column chro-
20
solid; ½aꢁ = ꢀ58.4 (c 1, CHCl3); IR (KBr): 3176,
matography (AcOEt–hexane 1:6). Yield: 92%; colorless
D
20
D
2401, 1060, 1009 cmꢀ1
;
1H NMR: d 7.83 (dd, J 1.6
oil; ½aꢁ = ꢀ111.2 (c 1, CHCl3); IR (film): 2401, 1216,
and 7.7 Hz, 1H), 7.76 (dd, J 1.6 and 7.7 Hz, 1H), 7.62
(td, J 1.6 and 7.7 Hz, 1H), 7.55 (td, J 1.59 and 7.7 Hz,
1H), 7.39 and 7.29 (AA0BB0 system, 4H), 5.83 (s, 1H),
4.78 (br s, OH), 2.39 (s, 3H); 13C NMR: d 142.1,
142.0, 138.9, 136.4, 133.1, 130.5, 130.4, 130.1, 129.6,
124.7, 117.5, 60.9, 21.4; MS (FAB+) m/z 272 [M+1]+;
HRMS [M+1]+: calcd for C15H13NO2S: 271.0667.
Found: 272.07452.
755 cmꢀ1
;
1H NMR: d 7.91–7.87 (m, 1H), 7.81–7.78
(m, 1H), 7.66–7.58 (m, 2H), 7.49 and 7.32 (AA0BB0 sys-
tem, 4H), 7.32 (d, J 7.8 Hz, 2H), 6.17 (s, 1H), 2.42 (s,
3H), 0.92 (s, 9H), 0.23 (s, 3H), 0.07 (s, 3H); 13C
NMR: d 141.9, 141.8, 140.8, 135.7, 131.9, 130.1, 128.4,
127.0, 125.5, 118.1, 59.0, 23.4, 21.2, 17.9, ꢀ3.1, ꢀ3.2.
Anal. Calcd for C21H27NO2SSi: C, 65.41; H, 7.06; N,
3.63; S, 8.32. Found: C, 64.91; H, 7.14; N, 3.59; S, 8.02.
4.5. (2R)-Mandelamide 5
4.9. (2R,(S)S)- and (2S,(S)S)-2-[2-(p-Tolylsulfinyl)phen-
yl]-2-(triisopropylsilyloxy)acetonitrile 8a and 8b
A solution of 271.4 mg (1 mmol) of cyanohydrin
(2R,(S)S)-4a in 10 mL of anhydrous CH2Cl2 at 0 ꢁC,
0.6 mL (9 mmol) of fluoroboric acid was added. The
mixture was stirred for 4 h at rt. Then 1.5 g (10 mmol)
of NaI was added and the resulting mixture stirred at
rt. After 15 h, the mixture was treated with 5 mL of
water, and extracted with CH2Cl2 (3 · 5 mL). The ex-
tracts were washed with aqueous NaHSO3, dried over
Na2SO4, and concentrated at a reduced pressure. The
residue was dissolved in THF and added onto a suspen-
sion of Ra–Ni in THF at rt. After 24 h, the reaction mix-
ture was filtered over Celite and the solvent evaporated.
The reaction was stirred at rt for 5 d and both diastereo-
isomers isolated by flash column chromatography
(AcOEt–hexane 1:8). Diastereoisomer (2R,(S)S)-8a:
20
yield: 65%; white solid; mp: 72–74 ꢁC; ½aꢁ = ꢀ89.4
D
(c 1.0, CHCl3); IR (KBr): 2401, 1215, 756 cmꢀ1
;
1H
NMR: d 7.99–7.94 (m, 1H), 7.85–7.82 (m, 1H), 7.63–
7.60 (m, 2H), 7.50 and 7.32 (AA0BB0 system, 4H), 6.15
(s, 1H), 2.42 (s, 3H), 1.21–1.11 (m, 3H), 1.08 (d, J
6.1 Hz, 9H), 0.99 (d, J 6.1 Hz, 9H); 13C NMR: d
142.3, 141.2, 140.6, 136.0, 131.0, 130.3, 129.9, 128.1,
126.9, 125.9, 118.1, 58.8, 21.4, 17.7, 17.6, 11.8. Anal.
Calcd for C25H35NO2SSi: C, 67.40; H, 7.78; N, 3.28;
S, 7.50. Found: C, 67.10; H, 7.60; N, 3.26; S, 7.38. Dia-
The product was purified by flash column chromatogra-
20
D
0.32, acetone) (from a 70:30 enantiomeric mixture of
phy (AcOEt–hexane 2:1). Yield: 55%. ½aꢁ = ꢀ7.8 (c
stereoisomer (2S,(S)S)-8b: yield: 20%; white solid; mp:
20
4a) {lit.21 [a]D = +73.0 (c 1.20, acetone)}.
78–79 ꢁC; ½aꢁ = ꢀ46.1 (c 1.0, CHCl3); IR (KBr):
D
1
2401, 1216, 756 cmꢀ1; H NMR: d 7.97–7.92 (m, 1H),
7.91–7.87 (m, 1H), 7.68–7.66 (m, 2H), 7.52 and 7.32
(AA0BB0 system, 4H), 6.13 (s, 1H), 2.41 (s, 3H), 1.25–
1.15 (m, 3H), 1.13 (d, J 5.8 Hz, 9H), 1.05 (d, J 6.2 Hz,
9H); 13C NMR: d 142.2, 141.9, 140.6, 135.7, 132.1,
130.5, 130.3, 127.6, 125.6, 125.5, 118.3, 59.2, 21.4,
17.7, 17.6, 11.8. Anal. Calcd for C25H35NO2SSi: C,
67.40; H, 7.78; N, 3.28; S, 7.50. Found: C, 67.18; H,
7.76; N, 3.24; S, 7.41.
4.6. General procedures for silylcyanation
A solution of 244.3 mg (1 mmol) of aldehyde 1 and
62.5 mg (1 mmol) Yb(OTf)3 in 5 mL of CH2Cl2 was stir-
red for 30 min at rt and then the corresponding silylcy-
anide (5 mmol) was added. The temperature and
reaction time are indicated in each case. In reactions
with TMSCN, the crude mixture was evaporated at a re-
duced pressure without additional work up. For the rest
of R3SiCN reagents, the resulting mixture was quenched
with a saturated aqueous NH4Cl and extracted with
CH2Cl2 (3 · 5 mL). The extracts were dried over
Na2SO4 and the solvent evaporated at a reduced pres-
sure. The residue was purified as indicated in each case.
4.10. General procedures for the deprotection of
silylcyanohydrins
To a solution of silylcyanohydrin (1 mmol) and AcOH
(5 mmol) in 5 mL of THF, TBAF (5 mmol) was added

´
J. L. Garcıa Ruano et al. / Tetrahedron: Asymmetry 16 (2005) 1963–1968
1968
´
8. Garcıa Ruano, J. L.; Martın Castro, A. M.; Rodrıguez, J.
H. Tetrahedron Lett. 1991, 32, 3195; Garcıa Ruano, J. L.;
´
´
portionwise and the reaction stirred at rt for 16 h. The
mixture was diluted with 5 mL of water and extracted
with Et2O (3 · 5 mL). The organic layer was washed
with brine (5 mL), dried over Na2SO4, and the solvent
evaporated under a reduced pressure.
´
´
Martın Castro, A. M.; Rodrıguez, J. H. J. Org. Chem.
1992, 57, 7235; Escribano, A.; Garcıa Ruano, J. L.;
´
´
´
Martın Castro, A. M.; Rodrıguez, J. H. Tetrahedron 1994,
50, 7567; Cifuentes Garcıa, M. M.; Garcıa Ruano, J. L.;
´
´
´
´
Martın Castro, A. M.; Rodrıguez Ramos, J. H.; Fernan-
dez, I. Tetrahedron: Asymmetry 1998, 9, 859.
´
´
Acknowledgements
´
9. Garcıa Ruano, J. L.; Carren˜o, M. C.; Toledo, M. A.;
Aguirre, J. M.; Aranda, M. T.; Fischer, J. Angew. Chem.,
We thank CAICYT (Grant BQU2003-04012) and MEC
(CTQ2004-02040/BQU) for financial support. One of us
(F.T.) thanks Comunidad Autonoma de Madrid for a
´
Int. Ed. 2000, 39, 2736; Garcıa Ruano, J. L.; Aleman, J.;
Soriano, J. F. Org. Lett. 2003, 5, 677; Garcıa Ruano, J. L.;
´
´
´
´
Aleman, J. Org. Lett. 2003, 5, 4513; Garcıa Ruano, J. L.;
Aranda, M. T.; Aguirre, J. M. Tetrahedron. 2004, 60,
5383.
´
´
predoctoral fellowship. Centro de Computacion Cientı-
fica (UAM) is gratefully acknowledged for computation
time.
10. Solladie, G.; Colobert, F.; Somny, F. Tetrahedron Lett.
1999, 40, 1227.
11. Nakamura, S.; Yasuda, H.; Watanabe, Y.; Toru, T.
Tetrahedron Lett. 2000, 41, 4157; Nakamura, S.; Yasuda,
H.; Watanabe, Y.; Toru, T. J. Org. Chem. 2000, 65,
8640.
References
12. Nakamura, S.; Oda, M.; Yasuda, H.; Toru, T. Tetrahedon
2001, 57, 8469.
1. Schwindt, M. A.; Belmont, D. T.; Carlson, M.; Franklin,
L. C.; Hendrickson, V. S.; Karrick, G. L.; Poe, R. W.;
Sobieray, D. M.; Van de Vusse, J. J. Org. Chem. 1996, 61,
9564.
2. Pirrung, M. C.; Shuey, S. W. J. Org. Chem. 1994, 59, 3890;
Ohta, S.; Yamashita, M.; Arita, K.; Kajiura, T.; Kawa-
saki, I.; Noda, K.; Izumi, M. Chem. Pharm. Bull. 1995, 43,
1294.
´
´
´
13. Garcıa Ruano, J. L.; Martın Castro, A. M.; Rodrıguez
Ramos, J. H. Rec. Res. Develop. Org. Chem. 2000, 4, 261.
14. Lai, C.-Y.; Mak, W.-L.; Chan, E. Y. Y.; Sau, Y.-K.;
Zhang, Q.-F.; Lo, S. M. F.; Williams, I. D.; Leung, W.-H.
Inorg. Chem. 2003, 42, 5863–5870.
15. Sarel, S.; Newman, M. S. J. Am. Chem. Soc. 1956, 78,
5416; Tsai, L.; Miwa, T.; Newman, M. S. J. Am. Chem.
Soc. 1957, 79, 2530; Becke, F.; Fleig, H.; Pa¨ssler, P.
Liebigs Ann. Chem. 1971, 749, 198; Houser, C. R.;
Hoffenberg, D. S. J. Org. Chem. 1955, 20, 1448; Hauser,
C. P.; Eby, C. J. J. Am. Chem. Soc. 1957, 79, 725.
3. Stelzer, U.; Effenberger, F. Tetrahedron: Asymmetry 1993,
4, 161.
4. Sadyandy, R.; Fernandes, R. A.; Kumar, P. ARKIVOC
2005, 3, 36; Kamal, A.; Shaik, A. A.; Sandbhor, M.;
Malik, M. S. Tetrahedron: Asymmetry 2004, 15, 3939;
Xiaobao, Y.; Shengjun, L.; Chengwen, H.; Hongbin, Z.
Tetrahedron 2003, 59, 8551; Yus, M.; Ramon, D. J.;
Prieto, O. Eur. J. Org. Chem. 2003, 15, 2745; Ginesta, X.;
Pasto, M.; Pericas, M. A.; Riera, A. Org. Lett. 2003, 5,
3001; Cho, B. T.; Kang, S. K.; Shin, S. H. Tetrahedron:
Asymmetry 2002, 13, 1209; Saotome, C.; Ono, M.; Akita,
H. Tetrahedron: Asymmetry 2000, 11, 4137; Effenberger,
F.; Roos, J. Tetrahedron: Asymmetry 2000, 11, 1085;
Sugai, T.; Kakeya, H.; Ohta, H. J. Org. Chem. 1990, 55,
4643.
5. Brunel, J.-M.; Holmes, I. P. Angew. Chem., Int. Ed. 2004,
43, 2752; He, K.; Zhou, Z.; Wang, L.; Li, K.; Zhao, G.;
Zhou, Q.; Tang, C. Tetrahedron 2004, 60, 10505; Chang,
C.-W.; Yang, C.-T.; Hwang, C.-D.; Uang, B.-J. Chem.
Commun. 2002, 54; You, J.-S.; Gau, H.-M.; Choi, M. C.
K. Chem. Commun. 2000, 1963; Hwang, C.-D.; Hwang,
D.-R.; Uang, B.-J. J. Org. Chem. 1998, 63, 6762.
6. He, B.; Chen, F.-X.; Li, Y.; Feng, X.; Zhang, G. Eur. J.
Org. Chem. 2004, 22, 4657; Avi, M.; Fechter, M. H.;
Gruber, K.; Belaj, F.; Poechlauer, P.; Griengl, H. Tetra-
hedron 2004, 60, 10411.
´
´
´
16. Garcıa Ruano, J. L.; Martın Castro, A. M.; Rodrıguez
Ramos, J. H. Tetrahedron Lett. 1996, 37, 4569.
17. Cunico, R. F.; Kuan, C. P. J. Org. Chem. 1990, 55, 4634.
18. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G.
E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.;
Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.;
Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.;
Strain, M. C.; Farkas, O. J.; Tomasi, J.; Barone, V.; Cossi,
M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.;
Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.;
Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz,
J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko,
A.; Piskorz, P.; Komaromi, R.; Gomperts, R. L.; Martin,
D. J.; Fox, T.; Keith, M. A.; Al-Laham, C. Y.; Peng, I.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.;
Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J.
A. Gaussian 98, Revision A.9, Gaussian, Inc.: Pittsburgh,
PA, 1998.
19. Becke, A. D. Phys. Rev. A 1988, 38, 3098; Lee, C.; Yang,
W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
20. Atomic coordinates and calculated energies for the main
stationary points are available from the corresponding
author.
´
´
7. Carren˜o, C.; Garcıa Ruano, J. L.; Martın, A. M.;
Pedregal, C.; Rodrıguez, J. H.; Rubio, A.; Sanchez, J.;
´
´
Solladie, G. J. Org. Chem. 1990, 55, 2120; Bueno, A. B.;
Carren˜o, M. C.; Fischer, J.; Garcıa Ruano, J. L.; Pen˜a, B.;
´
21. Wu, S. Y. Agricult. Biol. Chem. 1989, 53, 165.
Pen˜as, L.; Rubio, A. Tetrahedron Lett. 1991, 32, 3191.