Remote stereocontrol by the sulfinyl group: Mukaiyama aldol reactions of (S)-2-[2-(p-tolylsulfinyl)phenyl]acetaldehyde in the asymmetric synthesis of β-hydroxyacids and 1,3-diols

Article abstract of DOI:10.1016/j.tet.2006.10.010

(S)-2-[2-(p-Tolylsulfinyl)phenyl]acetaldehyde reacts with different O-silylated ketenethioacetals in the presence of Yb(OTf)₃ yielding β-hydroxythioesters in high yields and diastereoselectivities. The obtained compounds were readily transformed into β-hydroxyacids and their corresponding diols. These Mukaiyama aldol reactions are a direct evidence of the ability of the sulfinyl group to control 1,5- and 1,6-asymmetric induction processes.

Full text of DOI:10.1016/j.tet.2006.10.010

Tetrahedron 62 (2006) 12297–12305
Remote stereocontrol by the sulfinyl group: Mukaiyama aldol
reactions of (S)-2-[2-(p-tolylsulfinyl)phenyl]acetaldehyde in
the asymmetric synthesis of b-hydroxyacids and 1,3-diols
ꢀ
Jose L. Garcıa Ruano, M. Angeles Fernandez-Iban˜ez and M. Carmen Maestro
*
*
´
ꢀ
ꢀ
ꢀ
´
Departamento de Quımica Orgaꢀnica, Universidad Autoꢀnoma de Madrid, Cantoblanco, 28049-Madrid, Spain
Received 27 June 2006; revised 26 September 2006; accepted 5 October 2006
Available online 31 October 2006
Abstract—(S)-2-[2-(p-Tolylsulfinyl)phenyl]acetaldehyde reacts with different O-silylated ketenethioacetals in the presence of Yb(OTf)3
yielding b-hydroxythioesters in high yields and diastereoselectivities. The obtained compounds were readily transformed into b-hydroxyacids
and their corresponding diols. These Mukaiyama aldol reactions are a direct evidence of the ability of the sulfinyl group to control 1,5- and
1,6-asymmetric induction processes.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
achieved with aromatic aldehydes containing an ortho-sulfi-
nyl group,13–15 which include Mukaiyama reactions.13b,c,16
The aldol reaction is a powerful method of forming carbon–
carbon bonds in organic synthesis.1 The control of the abso-
lute configuration at the new stereogenic centers generated
in the reaction is an important task and hundreds of papers
and a number of excellent comprehensive reviews have ap-
peared covering this topic.2 Among these processes, the Mu-
kaiyama reaction3 has enjoyed a noteworthy development in
recent years, and it has become the reaction of choice to
attain high stereoselectivity, due to the possibility of using
chiral enolates,4 chiral substrates,5 and especially chiral
catalysts.6 The ability of the sulfinyl group to control the
face-selectivity in many different reactions is well-known.7
Concerning aldol reactions, the role of the sulfinyl group
has been investigated in reactions where this chiral auxiliary
is present at the nucleophilic enolate8–11 as well as at the
electrophile.12 The results obtained from all these studies re-
veal the efficiency of the sulfinyl group in the stereoselectiv-
ity control when it is separated by only one or two bonds
from the reaction center (1,2- and 1,3-asymmetric induction
processes). Less work has been done in the field of aldol
reactions involving remote stereofunctionalization (1,n-
asymmetric induction processes with n>3) controlled by
sulfoxides. The most important contributions have been
Some years ago we initiated a program to investigate the ef-
ficiency of the sulfinyl group to control the stereoselectivity
of reactions taking place at remote positions. We have
mainly studied 1,4-asymmetric induction processes con-
trolled by the sulfinyl group at the nucleophilic moiety,17
that proceed with an almost complete control of the stereo-
selectivity. On the other hand, we have reported the hydro-
cyanation of g-sulfinyl aromatic aldehydes, with the sulfur
function being at the electrophile.18 In this context, we
have also studied the first 1,5-asymmetric induction pro-
cesses controlled by the sulfinyl group starting from (S)-
ortho-(p-tolylsulfinyl)benzyl alkyl (and aryl) ketones and
their corresponding aldehydes,17e which involve reduction19a
and hydrocyanation19b reactions with aluminum reagents.
These reactions occurred with excellent stereoselectivities
and afforded diastereomerically enriched carbinols and cya-
nohydrins respectively, when they were performed in the
presence of Yb(OTf)3. We present herein the first results
on the stereoselective Mukaiyama reaction of (S)-2-[2-(p-
tolylsulfinyl)phenyl]acetaldehyde (1) with thioester O-silyl
enolates. They would allow to expand the scope of the 1,5-
asymmetric induction reactions controlled by the sulfinyl
group and would provide interesting synthetic intermediates
with a b-hydroxy carbonylic structure.
Keywords: Stereoselective Mukaiyama aldol reaction; 1,5- and 1,6-Asym-
metric induction; Chiral sulfoxide; Asymmetric synthesis of 3-hydroxy-
acids.
2. Results and discussion
* Corresponding authors. Tel.: +34 91 497 4701; fax: +34 91 497 3966;
e-mail addresses: joseluis.garcia.ruano@uam.es; carmen.maestro@
uam.es
Initially, we studied the reaction of the aldehyde 117e with
the O-silylated ketenethioacetal 2a20 at ꢀ78 ꢁC in the
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.10.010

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12298
presence of different Lewis acids (1.2 equiv). Mixtures of
the two possible diastereoisomeric adducts, epimers at the
hydroxylic carbon, were obtained in all cases (Table 1,
entries 1–4 and 6). Diastereoselectivity was low with
BF3$OEt2, TiCl4, AlCl3, and ZnI2 (Table 1, entries 1–4).
These reactions did not reach completion and a variable
amount of starting material was always recovered. No reac-
tion happened under MgCl2 catalysis, even at higher temper-
atures and longer reaction times (Table 1, entry 5). The best
stereoselectivity was achieved under Yb(OTf)3 catalysis
(Table 1, entry 6), as it had been also the case in the reactions
of other nucleophiles.19
trimethylsilyloxy ethylene, 2c, were not able to react with
1 in the presence of catalysts, even at room temperature.
Analogously, the reaction with ketene acetal 2d23 (Scheme
1) did not evolve, which was not unexpected because of
the low reactivity of this compound toward 2-(arylsulfinyl)-
naphthaldehydes, as had been reported by Toru.13b
OTBDMS
StBu
OTMS
H
OTMS
OEt
2b
2c
2d
Scheme 1.
Next, we tried to improve the conversion and stereoselectiv-
ity of the reactions performed under Yb(OTf)3 catalysis, by
changing the temperature, the solvent, the number of equiv-
alents of the reagents, and the reaction time. The best results
were obtained by lowering the temperature (Table 1, entries
6–8) and using acetonitrile21 as the solvent (entries 11–13),
which in its turn, also increased the reactivity. The use of
THF as the solvent (Table 1, entries 9 and 10) had no positive
influence. Under substoichiometric amounts of Yb(OTf)3
a significant decrease in both the reaction rate and the stereo-
selectivity, was observed, whereas an increase in the amount
of the Lewis acid (2 equiv) scarcely modified the reaction
rate. Under the optimum conditions, which were those of en-
try 12 (3 equiv of 2a, 1.2 equiv of Yb(OTf)3 in acetonitrile at
ꢀ40 ꢁC), a 94:6 mixture of diastereoisomers 3 and 4 could
be isolated in 86% yield. They were easily separated by
flash-column chromatography and the major compound 3
(de >98%) could be isolated in 79% yield.
Then, we studied the reactions of aldehyde 1 with the
substituted O-silylated ketenethioacetals (Z)-2e and (E)-2f,
which would allow the simultaneous formation of two ster-
eogenic centers in one step, providing information about the
influence of the remote sulfinyl group in determining the
configuration of both centers (1,5- and 1,6-asymmetric in-
duction processes). The reactions were performed under
the best conditions of Table 1, acetonitrile being used as
the solvent and Yb(OTf)3 as the catalyst. The results are col-
lected in Table 2.
All these reactions afforded only two out of the four possible
diastereoisomers. The reactions of sulfinylaldehyde 1 with
2e24 in the presence of 1.2 equiv of Yb(OTf)3, were per-
formed at different temperatures (Table 2, entries 1–3),
yielding mixtures of anti and syn a-methyl-b-hydroxy-
thioesters (5 and 6), the anti isomer 5 being the major one.
As expected, the selectivity slightly increased when the tem-
perature became lower and the reaction rate was also dimin-
ished. An increase in the number of equivalents of the
electrophile had some influence on the reaction rate (shorter
reaction times were needed) but not on the stereoselectivity
(Table 2, entries 3–5). The use of dichloromethane as the
An increase in the size of the silyloxy group had no sig-
nificant influence on the reactivity or on the selectivity of
these reactions. Thus, tert-butyldimethylsilyl derivative
2b22 (Scheme 1) gave almost identical results to 2a under
similar conditions. Less nucleophilic species, such as
Table 1. Reactions of aldehyde 1 with 2a catalyzed by Lewis acids
OTMS
Tol
StBu
2a (1.2 equiv)
S
SOTol
SOTol
O
O
OH
O
HO
H
H
+
Lewis acid (1.2 equiv)
StBu
StBu
1
3
4
H
O
Entry
Solvent
Lewis acid
Temperature (ꢁC)
Time
Conversion (%)a
3:4 Ratioa
b
1
2
3
4
5
6
7
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
BF3$OEt2
TiCl4
AlCl3
ZnI2
MgCl2
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
ꢀ78
ꢀ78
ꢀ78
ꢀ78
rt
ꢀ78
ꢀ40
0
2 h
2 h
2 h
2 h
5 days
2 h
2 h
84
87
34
72
—
60
83
86
98
98
85
100
100
55:45
61:39
66:34
72:28
—
88:12
73:27
61:39
82:18
77:23
94:6
2 h
9c
10
11
12c
13
ꢀ40
62 h
16 h
2 h
1.5 h
2 h
THF
rt
CH3CN
CH3CN
CH3CN
ꢀ40
ꢀ40
Reflux
94:6d
83:17
Determined by 1H NMR spectroscopy.
2 equiv was used.
3 equiv of 2a.
a
b
c
d
A 77:23 ratio of 3 and 4 was observed by using 0.5 equiv of Yb(OTf)3.

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Table 2. Reactions of 1 with O-silylated ketenethioacetals 2e and 2f
R1 OTBDMS
Tol
SOTol
SOTol
StBu
2e,f
S
O
R2
O
HO
H
HO
H
O
+
StBu
StBu
Yb(OTf)3 (1.2 equiv)
CH3CN
Me
H
H Me
1
H
O
6
5
2e (R1=H; R2=Me)
2f (R1=Me; R2=H)
Entry
Enolate (equiv)
Temperature (ꢁC)
Time (h)
Conversiona (%)
5:6a
1
2
3
4
2e (3)
2e (3)
2e (3)
2e (1.5)
2e (1.5)
2e (1.5)
2e (1.5)
2f (3)
ꢀ40
ꢀ10
0
0
0
0
rt
0
0
ꢀ40
62
15
3
3
6
3
3
3
7
120
55
98
78:22
74:26
72:28
72:28
72:28
46:49e
67:33
83:17
83:17
83:17
100b
52
5
93
—
6c
7
d
62
100f
80
8
9
10
2f (1.5)
2f (3)
73
Determined by 1H NMR spectroscopy.
Combined yield: 71%.
CH2Cl2 as the solvent.
Non-evaluated.
A third isomer (5%) was detected.
Combined yield: 73%.
a
b
c
d
e
f
solvent decreased the stereoselectivity, because it afforded
nearly equimolar mixtures of anti-5 and syn-6 isomers,
along with a third isomer that could be detected by H
NMR (Table 2, entry 6). The best reaction conditions found
for 2e (Table 2, entries 3 and 5) were also explored with 2f.24
In this case the major isomer also was anti-5, but the stereo-
selectivity was slightly higher, 83(5):17(6) at 0 ꢁC (Table 2,
entries 8 and 9). When the temperature was lower, the reac-
tion time increased significantly and no change in the stereo-
selectivity was observed.
experience was not conclusive because the composition
of the resulting mixture (ca. 1:1) was not identical to that
of the starting one (ca. 1:2), thus suggesting partial epi-
merization of the a-carbon to the thioester group under
the reaction conditions. Despite this result, we assumed
that both isomers exhibit the same configuration at the
hydroxylic carbon because 2e and 2f must attack at the
same face of the carbonyl group at compound 1, chelated
with Yb(OTf)3, as it was the case of compound 2a, with
a stereoselectivity presumably higher in the former cases
due to the bulkier size of the nucleophilic carbon at 2e
and 2f.
1
Diastereoisomeric mixtures obtained in these reactions
could not be separated by column chromatography. How-
ever, the major diastereomer 5 could be obtained as a pure
compound by crystallization in 40% yield from 2e and
51% yield from 2e (Table 2, entries 3 and 8, respectively).
All the attempts at ꢀ40 ꢁC in THF, in the presence of
TBAF as a fluoride source, with the aim of obtaining the
syn adduct 6 as the major one,24,25 were unsuccessful.
(4) The absolute configuration of the major anti-5 isomer
was unequivocally established as [2R,3R,(S)S] by X-ray
diffraction studies.26 Therefore, according to the above
considerations we assign the [2S,3R,(S)S] configuration
to the minor syn-6.
Once the configurational assignment of the adducts in the
Mukaiyama reactions was unequivocally established, we
can conclude that the stereocontrol was very high (from
2a) or complete (from 2e and 2f) at the benzylic carbon
(1,5-asymmetric induction process) but only moderate at
the a-carbon to the ester group (1,6-asymmetric induction
process).
Configurational assignment of compounds 3–6 was carried
out as follows:
(1) The configuration of 3 was unequivocally established as
[3R,(S)S] by chemical correlation with alcohol 10 (see
later). It allowed us to assign the [3S,(S)S] configuration
for compound 4.
(2) The oxidation with m-CPBA of the 33(5):67(6) mixture
gave two diastereoisomeric sulfones with the same dia-
stereoisomeric ratio as the starting sulfoxides. This
result indicated that hydroxysulfoxides 5 and 6 only
differed in the configuration of one of the two chiral
carbons.
The observed stereoselectivity can be explained by assum-
ing the formation of an eight-membered chelated species be-
tween the Yb(OTf)3 and the carbonyl and sulfinyl oxygens at
the substrate, as it had been postulated to explain the results
obtained in the reduction19a and hydrocyanation19b of this
type of ketosulfoxides. Two conformations can be proposed
for this chelated species, B (Fig. 1) as the most stable one,
because conformation A must be strongly unestabilized by
steric interactions between the ring and the ligands of the
metal. The approach of nucleophile 2a or 2b at the pro-R
face of the carbonyl group in its most stable conformation
(3) The oxidation with PCC of the above mixture of 5 and 6
afforded two diastereoisomeric ketones, which initially
suggested that the starting sulfoxides were epimers at
the a-carbon to the thioester group. However, this

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12300
Tol
S
Tol
S
H
SOTol
H
O
H
2a or 2b
H
Yb
O
Yb
t
OH
CH2
O
1-A
H
O
SBu
t
H
SBu
O
Si O
TS-1
3
Tol
S
Tol
S
Yb
O
O
H
Yb
O
1-B
SOTol
H
O
H
H
O
H
CH2
OH
t
2a or 2b
SBu
H
t
SBu
TS-2
Figure 1. Favored approach of 2a and 2b in Mukaiyama aldol reaction of chelated aldehyde 1.
Si = TMS or TBDMS
Si O
4
would yield compound 3 through TS-1, whereas the attack at
the pro-S face would afford 4 through TS-2. From Figure 1,
it is evident the lower stability of TS-2, which would explain
the formation of 3 as the major diastereoisomer.
olefinic carbon, present in TS-4, thus explaining the ob-
served predominance of the anti-compounds. From Figure 2
it is easily understood that the E or Z configuration of the
enolates scarcely affects the stereochemical results.24,27
From the above figure it can also be inferred that TS-2 would
be too unstable for substituted enolates, such as 2e or 2f,
which should evolve in a completely stereoselective manner
by attack at the pro-R face of the chelated carbonyl through
transition states similar to TS-1. This fact is in agreement
with the complete control of the diastereoselectivity at the
hydroxylic center observed for these reactions (Table 2).
Different TS can be postulated (Fig. 2) differing in the rela-
tive arrangement of the C¼C and C¼O groups. TS-3 and
TS-5 must be highly unstable due to the strong steric inter-
actions between the ring at 1 and the substituents at 2e and
2f adopting an antiperiplanar arrangement with respect to
the C¼O group. Therefore, the favored transition states are
TS-4 and TS-40, both orientating the H in such an arrange-
ment. As these transition states differ only in the nucleophile
face that attacks at the carbonyl group, the obtained products
will have the opposite configuration at the attacking nucleo-
philic carbon. The fact that anti-5 is obtained as the major
isomer suggest that the steric interaction of the methylene
at the aldehyde with the tetrahedral CH3 group at the nucleo-
phile, present in TS-40, is stronger than that with the flat
As the last step of this research we studied the removal of the
chiral auxiliary. The reaction of a mixture of 3 and 4 with
Raney nickel afforded 4-phenyl-1,3-butanediol (7), indicat-
ing that the reagent had produced hydrogenolysis of the C–S
bond as well as the reduction of the thioester group.24,28 Re-
action of diastereoisomerically pure 3 with Raney nickel un-
der hydrogen atmosphere, yielded compound 7 (60% yield)
exhibiting a [a]D value of +19.0. The protection of the OH
group at 3 as a TIPS derivative and further reduction with
Raney nickel and desilylation (Scheme 2) also provided
compound 7, but in this case with an [a]D value of +21.0.
This fact suggests that the direct reduction of 3 had taken
place with a slight epimerization at the hydroxylic center,
as it had been previously reported for other sulfinyl alco-
hols.29 Compound 7, obtained by the indirect way, was trans-
formed into 1030 (Scheme 2). The 1H NMR studies on
Mosher’s esters31 of compound 10 allowed us to establish
the R configuration at its hydroxylic carbon as well as its
high optical purity (ee >98%). The same configuration
must be assigned to its precursor 7. Therefore, the absolute
configuration of 3 was indirectly assigned as [3R,(S)S],
whereas that of [3S,(S)S] must be assigned to epimer 4.
Tol
Tol
SOTol
S
S
t
Y
COSBu
SOTol
OTIPS
COS Bu
SOTol
OH
H
H
H
Y'
Yb
TIPSOTf,
O
Yb
O
H
O
OH
H
t
H
O
H3C
O
Y
2,6-lutidine,
CH3
H
t
S Bu
CH2Cl2, rt
CH3
TS-4
H
H
Y'
anti-5
8
3
90%
Raney Ni / H2
EtOH, rt
91%
Raney Ni / H2
EtOH, rt
60%
TS-3
Tol
Tol
SOTol
TBAF,
CH2Cl2, rt
77%
OH
OH
S
S
OTIPS
H
H
Y
CH3
Yb
CH3
OH
CH3
Yb
OH
H
H
O
H
H
O
Y'
7
9
H
O
O
t
H
COSBu
syn-6
Y
Y'
H
Ref. 30
OH
H
H
TS-5
TS-4'
Mosher´s esters
t
2e (Y'=SBu , Y=OTBDMS)
2f (Y=SBu , Y'=OTBDMS)
t
OTBDMS
(R)-10 (>98% ee)
Figure 2. Favored approach of 2e and 2f in Mukaiyama aldol reaction of
chelated aldehyde 1.
Scheme 2.

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12301
Desulfinylation and reduction of the thioester moiety with
3. Experimental
3.1. General methods
Raney nickel in hydrogen atmosphere were also performed
on diastereoisomerically pure 5, yielding a 83:17 diastereo-
isomeric mixture of diols 11 and 12 as the result of the partial
racemization of the hydroxylic center (Scheme 3). The anti
stereochemistry of diol 11 was established by comparison of
its 1H NMR data with those previously reported for this com-
pound.32 It can be obtained in its diastereoisomeric pure
form by an initial protection of 5 as triisopropylsilyl deriva-
tive 13, reduction with Raney nickel into 14 and final desily-
lation, as it is indicated in Scheme 3.
NMR spectra were obtained in CDCl3 solutions at 300 and
1
75 MHz for H and 13C NMR, respectively (J values are
given in hertz). Melting points were measured in open cap-
illary tubes. Mass spectra (MS) were obtained by FAB+, ES+
(MeOH+0.1% formic acid) or EI+ with ionizing voltage of
70 eV. The des were evaluated by integration of well-sepa-
rated signals of the 1H NMR spectra. All reactions were car-
ried out under an argon atmosphere in anhydrous solvents.
THF was distilled from sodium-benzophenone under argon.
CH2Cl2 was distilled from P2O5. Flash-column chromato-
graphy was performed using silica gel (230–400 mesh).
The silyl thioenolates were synthesized according to the
described procedures.
Another interesting transformation of hydroxythioester 5
into the corresponding desulfinylated a-methyl-b-hydroxy-
acid, has been performed (Scheme 4). Hydrolysis of the thio-
ester was readily achieved with lithium hydroxide in THF/
H2O.33 However, the reaction of the obtained acid 15 with
Raney nickel, in order to remove the sulfinyl group, was un-
successful and the resulting product was unrecoverable. We
then protected the sulfinylhydroxyacid 15 as its triisopropyl-
silyl derivative 16, which reacted satisfactorily with Raney
nickel in very high yield and afforded compound 17, without
apparent racemization at hydroxylic carbon. Desilylation of
17 with HF/pyridine34 at room temperature afforded the
expected hydroxyacid 18 (Scheme 4).
3.2. Mukaiyama aldol reaction. General procedure
A solution of aldehyde 1 (0.39 mmol) and Yb(OTf)3
(0.46 mmol) in CH3CN (3.4 mL) was stirred at room temper-
ature for 30 min under an argon atmosphere. Then, this solu-
tion was cooled to the temperature indicated in each case
and the corresponding silyl enol thioester (1.17 mmol) was
added. The solution was stirred at the same temperature for
the indicated time and then, quenched with an aqueous 1 M
solution of HCl. The organic layer was separated and the
aqueous phase extracted with CH2Cl2 (3.3 mL). The com-
bined organic extracts were dried (Na2SO4) and concentrated
in vacuo. The residue was purified by flash-column chroma-
tography using the eluent specified for each case.
As a conclusion, we have demonstrated that the stereo-
selectivity of Mukaiyama aldol reactions of aldehydes and
O-silylated ketenethioacetals can be efficiently controlled
by a remote sulfinyl group. The essential role of Yb(OTf)3
as a Lewis catalyst for achieving high level of diastereo-
selectivity has also been established for these 1,5-asym-
metric induction processes. Desulfinylation and further
transformation of the resulting isomers provided a new
access to interesting carbinols and b-hydroxyacids.
3.2.1. S-tert-Butyl [3R,(S)S]-3-hydroxy-4-[2-(p-tolylsulfi-
nyl)phenyl]butanethioate (3). Compound 3 was obtained
SOTol
OH
O
OH
Raney Ni / H2
OH
+
EtOH, rt
65%
t
OH
OH
OH
S Bu
5
12 (17)
11 (83)
TIPSOTf, CH2Cl2
2,6-lutidine, rt
95%
TBAF, rt
76%
SOTol
OTIPS
O
Raney Ni / H2
OTIPS
t
EtOH, rt
91%
S Bu
13
14
Scheme 3.
SOTol
OH
SOTol
OTIPS
COOTIPS
SOTol
OH
O
TIPSOTf (3 equiv.);
LiOH, rt
THF / H2O
98%
O
2,6-lutidine (4 equiv.);
t
S Bu
OH
CH2Cl2; rt
5
15
16
73%
Raney Ni
EtOH, rt
94%
HF / Py;
THF; rt
68%
OH
O
OTIPS
COOTIPS
OH
18
17
Scheme 4.

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12302
from 2a as a 94:6 mixture of 3 and 4 following the above
general procedure at ꢀ40 ꢁC for 90 min. Combined yield:
86%. Diastereomerically pure 3 was separated by flash-col-
umn chromatography (ethyl acetate–hexane 1:2) as a color-
less oil. Yield: 79%; [a]2D0 ꢀ60.4 (c 0.2, CHCl3); IR (film):
7.47 and 7.25 (AA0BB0 system, 4H), 7.46–7.39 (m, 2H),
7.30 (m, 1H), 4.14 (ddt, J 7.3, 6.9, and 5.3 Hz, 1H), 2.95
(dd, J 14.1 and 6.9 Hz, 1H), 2.89 (dd, J 14.1 and 5.7 Hz,
1H), 2.57 (dd, J 15.6 and 4.8 Hz, 1H), 2.52 (dd, J 15.6 and
7.3 Hz, 1H), 2.37 (s, 3H), 1.45 (s, 9H). 13C NMR: d 199.9,
143.6, 141.8, 141.1, 136.4, 131.5, 131.2, 130.1, 127.8,
126.1, 125.9, 68.5, 50.0, 48.6, 38.1, 29.7, 21.4; MS (FAB+)
m/z 391 (100) [M+1]+, 373 (12) [M+–H2O], 307 (23), 91
(20), 89 (20); HRMS [M+1]+: Calcd for C21H27O3S2:
391.1401; found, 391.1408.
0.59 mmol) was added to a solution of monoprotected diol
9 (0.12 mmol) in dichloromethane (1 mL) under an argon
atmosphere. The reaction mixture was stirred for 18 h
and then, quenched with an aqueous 1 M solution of HCl and
extracted with dichloromethane (3ꢂ3 mL). The organic
extracts were washed with brine, dried (Na2SO4), and the
solvent was evaporated. The residue was purified by flash-
column chromatography (ethyl acetate–hexane 1:1). Yield:
1
3386, 1597, 1216, 704 cmꢀ1; H NMR: d 7.82 (m, 1H),
1
77%, colorless oil; [a]2D0 +21.0 (c 0.6, CHCl3); H NMR:
d 7.35–7.20 (m, 5H), 4.09 (m, 1H), 3.92–3.78 (m, 2H),
2.82 (dd, J 13.3 and 5.2 Hz, 1H), 2.76 (dd, J 13.3 and
7.7 Hz, 1H), 2.38 (br s, 2H), 1.80–1.72 (m, 2H); 13C
NMR: d 137.9, 129.4, 128.6, 126.6, 73.0, 61.7, 44.3, 37.7.
3.2.6. S-tert-Butyl [3R,(S)S]-4-[2-(p-tolylsulfinyl)phenyl]-
3-(triisopropylsilyloxy)butanethioate (8). Triisopropylsilyl
trifluoromethanesulfonate (72.9 mL, 0.27 mmol) was added
to a solution of 3 (0.18 mmol) in anhydrous dichloromethane
(3 mL) and 2,6-lutidine (41.6 mL, 0.36 mmol) under an
argon atmosphere, and the mixture was stirred at room tem-
perature for 16 h. The reaction mixture was quenched with
water, extracted with CH2Cl2 (3ꢂ3 mL), dried (Na2SO4),
and the solvent was evaporated. The residue was purified
by flash-column chromatography (ethyl acetate–hexane
1:4) affording pure 8 as a colorless oil. Yield: 90%; [a]D20
ꢀ94.0 (c 3.9, CHCl3); IR (film): 2961, 2866, 1680,
3.2.2. S-tert-Butyl [3S,(S)S]-3-hydroxy-4-[2-(p-tolylsulfi-
nyl)phenyl]butanethioate (4). Compound 4 was obtained
as the minor adduct, following the above general procedure,
from 2a at different experimental conditions (see Table 1). It
was characterized from a 61:39 mixture of 3 and 4, obtained
by flash-column chromatography (ethyl acetate–hexane
1
1:2). H NMR: (representative parameters) d 4.13 (m, 1H),
2.94 (dd, J 14.5 and 7.0 Hz, 1H), 2.85 (dd, J 14.0 and
5.4 Hz, 1H), 2.65–2.43 (m, 2H); 13C NMR: (representative
parameters) d 199.8, 69.4, 51.0.
1462 cmꢀ1 1H NMR: d 7.98 (m, 1H), 7.49 and 7.23
;
(AA0BB0 system, 4H), 7.45–7.32 (m, 3H), 4.51 (q,
J 6.0 Hz, 1H), 3.00 (dd, J 14.3 and 6.6 Hz, 1H), 2.95 (dd,
J 14.3 and 6.2 Hz, 1H), 2.48 (dd, J 14.9 and 5.6 Hz, 1H),
2.42 (dd, J 14.9 and 6.4 Hz, 1H), 2.35 (s, 3H), 1.43 (s,
9H), 0.96 (m, 21H); 13C NMR: d 197.7, 143.9, 142.0,
141.8, 136.1, 131.2, 130.7, 130.0, 127.7, 126.2, 124.7,
69.6, 51.4, 48.2, 39.1, 29.7, 21.4, 18.0, 12.5; MS (FAB+)
m/z 547 (50) [M+1]+, 503 (100) [M+ꢀCH(CH3)2]; HRMS
[M+1]+: Calcd for C30H47O3S2Si: 547.2735; found,
547.2746.
3.2.3. S-tert-Butyl [2R,3R,(S)S]-3-hydroxy-2-methyl-4-
[2-(p-tolylsulfinyl)phenyl]butanethioate (5). Compound
5 was obtained from 2e as a 83:17 mixture of 5 and 6, follow-
ing the above general procedure at 0 ꢁC for 3 h. The mixture
was purified by flash-column chromatography (ethyl ace-
tate–hexane 1:1). Combined yield: 73%. Crystallization
(ethyl acetate–hexane) afforded pure 5 as a white solid.
Yield: 51%. Mp: 108–110 ꢁC; [a]D20 ꢀ85.5 (c 2.5, CHCl3);
(m, 1H), 7.47 and 7.25 (AA0BB0 system, 4H), 7.42–7.31
(m, 3H), 3.73 (m, 1H), 3.08 (d, J 7.7 Hz, 1H), 2.98 (dd,
J 14.1 and 4.4 Hz, 1H), 2.91 (dd, J 14.1 and 8.4 Hz, 1H),
2.67 (m, 1H), 2.37 (s, 3H), 1.43 (s, 9H), 1.24 (d, J 6.9 Hz,
3H); 13C NMR: d 204.5, 143.7, 141.7, 141.1, 137.4, 131.2,
131.1, 130.0, 127.7, 126.2, 125.7, 74.2, 53.3, 48.5, 37.1,
29.7, 21.3, 15.0; MS (FAB+) m/z 405 (100) [M+1]+, 351
(19), 259 (30), 91(17), 89(9); HRMS [M+1]+: Calcd for
C22H29O3S2: 405.1558; found: 405.1572. Anal. Calcd for
C22H28O3S2: C, 65.32; H, 6.98; S, 15.85. Found: C, 65.27;
H, 6.88; S, 15.43.
1
IR (film): 3372, 2924, 1675, 1455 cmꢀ1; H NMR: d 7.75
3.2.7. (R)-4-Phenyl-3-(triisopropylsilyloxy)butan-1-ol
(9). An excess amount of Raney nickel was added, under hy-
drogen atmosphere, to a solution of silylated alcohol 8
(85 mg, 0.15 mmol) in ethanol (2 mL). The reaction mixture
was stirred at room temperature for 16 h, and then, filtered
through a Celite pad, which was washed with ethanol, and
the solvent was evaporated. Yield: 91%, colorless oil; [a]D20
ꢀ15.0 (c 0.6, CHCl3); IR (film): 3355, 3063, 2866,
1
1463 cmꢀ1; H NMR: d 7.22–7.07 (m, 5H), 4.25 (m, 1H),
3.84 (m, 1H), 3.64 (m, 1H), 2.95 (dd, J 13.2 and 4.9 Hz,
1H), 2.77 (dd, J 13.2 and 9.4 Hz, 1H), 2.48 (m, 1H, OH),
1.72 (m, 1H), 1.48 (m, 1H), 1.03 (m, 21H); 13C NMR:
138.2, 129.3, 128.4, 126.0, 73.5, 59.9, 43.2, 36.4, 18.1,
12.6; MS (FAB+) m/z 323 (27) [M+1]+, 279 (20)
[MꢀCH(CH3)2]+, 131 (100), 91 (24); HRMS [M+1]+: Calcd
for C19H35O2Si: 323.2406; found, 323.2396.
3.2.4. S-tert-Butyl [2S,3R,(S)S]-3-hydroxy-2-methyl-4-[2-
(p-tolylsulfinyl)phenyl]butanethioate (6). Compound 6
was obtained as the minor adduct from 2e, following the
above general procedure at different experimental condi-
tions (see Table 2). It was characterized from a 37:63 mix-
ture of 5 and 6 obtained by flash-column chromatography
1
(ethyl acetate–hexane 1:1). H NMR: (representative para-
3.2.8. (2R)-4-(tert-Butyldimethylsilyloxy)-1-phenyl-
butan-2-ol (10). It was obtained from diol 7, following the
reported procedure30 [a]D20 +10.6 (c 0.6, CHCl3).
meters) d 3.89 (m, 1H), 2.91–2.83 (m, 2H), 2.60 (dq, J 6.9
and 4.8 Hz, 1H), 1.45 (s, 9H), 1.23 (d, J 6.9 Hz, 3H); 13C
NMR: (representative parameters) d 204.3, 74.1, 53.4,
48.2, 36.4, 29.6, 12.7.
3.2.9. S-tert-Butyl [2R,3R,(S)S]-2-methyl-4-[2-(p-tolylsul-
finyl)phenyl]-3-(triisopropylsilyloxy)butanethioate (13).
3.2.5. (3R)-4-Phenylbutane-1,3-diol35 (7). A 1 M solution
of tetrabutylammonium fluoride in THF (0.59 mL,
Triisopropylsilyl
0.25 mmol) was added to a solution of 5 (0.16 mmol) in
trifluoromethanesulfonate
(66.8 mL,

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J. L. Garcıa Ruano et al. / Tetrahedron 62 (2006) 12297–12305
12303
anhydrous dichloromethane (3 mL) and 2,6-lutidine
(38.5 mL, 0.33 mmol) under an argon atmosphere, and the
mixture was stirred for 24 h at room temperature. The reac-
tion mixture was quenched with water, extracted with
CH2Cl2 (3ꢂ3 mL), dried (Na2SO4), and the solvent was
evaporated. The residue was purified by flash-column chro-
matography (ethyl acetate–hexane 1:4) affording pure 13 as
a colorless oil. Yield: 95%; [a]2D0 ꢀ110.0 (c 4.1, CHCl3); IR
(film): 2943, 2866, 1680, 1462 cmꢀ1; 1H NMR: d 7.95–7.92
(m, 1H), 7.49 and 7.34 (AA0BB0 system, 4H), 7.42–7.29 (m,
3H), 4.49 (dt, J 8.7 and 3.0 Hz, 1H), 2.85–2.29 (m, 2H), 2.76
(dd, J 14.3 and 2.6 Hz), 2.34 (s, 3H), 1.46 (s, 9H), 1.23 (d,
J 7.0 Hz, 3H), 1.04 (m, 7H), 1.89 (m, 14H); 13C NMR:
d 201.6, 144.6, 142.2, 141.4, 137.1, 130.9, 130.5, 129.9,
127.6, 125.9, 124.5, 74.5, 55.0, 48.1, 34.5, 29.8, 21.3,
18.0, 17.9, 17.6, 12.6, 12.3, 9.8. MS (ES+): 583 (32), 561
(47), 471 (100), 387 (22); HRMS [M+23]+: Calcd for
C31H48O3NaSiS2: 583.2706; found, 583.2704. [M+1]+:
Calcd for C31H49O3SiS2: 561.2886; found, 561.2914.
purified by flash-column chromatography (ethyl acetate–
hexane 1:1) affording a 83:17 mixture of 11+12. Yield:
65%, colorless oil; H NMR: (representative parameters of
12) d 4.10–4.04 (m, 1H), 2.78 (d, J 6.9 Hz, 2H), 1.95–1.87
(m, 1H), 1.04 (d, J 6.9 Hz, 3H).
1
3.2.13. [2R,3R,(S)S]-3-Hydroxy-2-methyl-4-[2-(p-tolyl-
sulfinyl)phenyl]butanoic acid (15). A solution of lithium
hydroxide (1.02 mmol) in H2O (1.5 mL) was added to a solu-
tion of 5 (0.17 mmol) in THF (1.5 mL). The reaction mixture
was stirred at room temperature for 16 h, and then it was
acidified with an aqueous 1 M solution of HCl, and extracted
with dichloromethane (3ꢂ3 mL). The organic extracts were
washed with brine, dried (Na2SO4), and the solvent evapo-
rated. Yield: 98%, colorless oil; [a]2D0 ꢀ28 (c 0.5, CHCl3);
1
IR (film): 3356, 2923, 1720, 1594 cmꢀ1; H NMR: d 7.65
(dd, J 8.0 and 1.3 Hz, 1H), 7.44 and 7.23 (AA0BB0 system,
4H), 7.41–7.30 (m, 3H), 3.82 (m, 1H), 3.07 (dd, J 14.1 and
8.5 Hz, 1H), 2.98 (dd, J 14.1 and 4.1 Hz, 1H), 2.59 (q,
J 7.0 Hz, 1H), 2.35 (s, 3H), 1.25 (d, J 7.2 Hz, 3H);
13C NMR: d 178.2, 143.1, 141.9, 139.9, 137.6, 131.4,
130.1, 127.8, 126.2, 125.9, 73.5, 44.7, 37.0, 21.4, 14.3;
MS (EI+) m/z 315 (75) [(M+1)ꢀH2O]+, 297 (15), 241 (33),
91 (71); HRMS [(M+1)ꢀH2O]+: Calcd for C18H19O3S:
315.1055; found: 315.1053.
3.2.10. (2S,3R)-2-Methyl-4-phenyl-3-(triisopropylsilyl-
oxy)butan-1-ol (14). An excess amount of Raney nickel was
added, under hydrogen atmosphere, to a solution of the sily-
lated alcohol 13 (128 mg, 0.23 mmol) in ethanol (4 mL).
The reaction mixture was stirred at room temperature for
17 h, and then filtered through a Celite pad, which was
washed with ethanol, and the solvent was evaporated. The
residue was purified by flash-column chromatography (ethyl
acetate–hexane 1:4) affording pure 14 as a colorless oil.
Yield: 91%; [a]2D0 +11 (c 6.4, CHCl3); IR (film): 3384,
3.2.14. Triisopropylsilyl [2R,3R,(S)S]-2-methyl-4-[2-(p-
tolylsulfinyl)phenyl]-3-(triisopropylsilyloxy)butanoate
(16). Triisopropylsilyl trifluoromethanesulfonate (142.0 mL,
0.52 mmol) was added to an anhydrous solution of hydroxy-
acid 15 (0.17 mmol) and 2,6-lutidine (82 mL, 0.70 mmol)
in dichloromethane (3 mL), under an argon atmosphere.
The reaction mixture was stirred at room temperature for
16 h, and then, quenched with water and extracted with di-
chloromethane (3ꢂ3 mL). The organic extracts were dried
(Na2SO4) and the solvent evaporated. The residue was
purified by flash-column chromatography (ethyl acetate–
hexane 1:4). Yield: 73%, colorless oil; [a]2D0 ꢀ72.0
1
3063, 2866, 1463 cmꢀ1; H NMR: d 7.23–7.07 (m, 5H),
4.15 (ddd, J 8.7, 5.5, and 2.4 Hz, 1H), 3.90 (dd, J 11.0 and
3.9 Hz, 1H), 3.46 (m, 1H), 2.94 (dd, J 13.6 and 5.6 Hz,
1H), 2.85 (dd, J 13.6 and 9.1 Hz, 1H), 2.54 (br s, 1H), 1.57
(m, 1H), 1.03 (m, 7H), 0.98 (m, 17H); 13C NMR: d 138.4,
129.2, 128.4, 126.2, 78.7, 64.4, 41.5, 36.8, 18.2, 18.1, 17.6,
14.8, 12.8, 12.3; HRMS (ES+) [M+23]+: Calcd for
C20H36O2NaSi: 359.2376; found, 359.2369. [M+1]+, Calcd
for C20H37O2Si: 337.2557; found, 337.2558.
(c 3.1, CHCl3); IR (film): 2945, 2867, 1715, 1464 cmꢀ1
;
1H NMR: d 7.80 (m, 1H), 7.45 and 7.20 (AA0BB0 system,
4H), 7.42–7.27 (m, 3H), 4.62 (m, 1H), 3.02–2.87 (m, 2H),
2.54 (m, 1H), 2.33 (s, 3H), 1.33–1.26 (m, 5H), 1.07 (m,
19H), 0.89 (m, 21H); 13C NMR: d 173.8, 144.8, 142.6,
141.5, 137.0, 130.5, 130.2, 129.9, 127.6, 126.0, 124.2,
74.1, 47.2, 34.7, 21.3, 17.9, 17.8, 12.7, 11.9; MS (FAB+)
m/z 645 (27) [M+1]+, 601 (100) [MꢀSiCH3]+; HRMS
[M+1]+: Calcd for C36H61O4SSi2: 645.3829; found:
645.3821.
3.2.11. (2S,3R)-2-Methyl-4-phenylbutane-1,3-diol (11).32
A 1 M solution of tetrabutylammonium fluoride in THF
(0.95 mL, 0.95 mmol) was added to a solution of mono-
protected diol 14 (0.19 mmol) in dichloromethane (2 mL)
under argon atmosphere. The reaction mixture was stirred
at room temperature for 60 h and then filtered through a silica
gel pad, which was washed with ethanol, and the solvent
was evaporated. The residue was purified by flash-column
chromatography (ethyl acetate–hexane 1:1). Yield: 76%,
colorless oil; [a]D20 +49 (c 2.3, CHCl3). [Lit.32 [a]D25 +59 (c
3.2.15. Triisopropylsilyl [2R,3R]-2-methyl-4-phenyl-3-
(triisopropylsilyloxy)butanoate (17). An excess of acti-
vated Raney nickel was added to a solution of 16
(0.12 mmol) in ethanol (2 mL). The reaction mixture was
stirred at room temperature for 14 h under hydrogen atmo-
sphere and then it was filtered through a Celite pad, which
was washed with ethanol, and the solvent was evaporated.
Yield: 94%, colorless oil; [a]2D0 ꢀ6.4 (c 1.7, CHCl3); IR
1
0.27, CHCl3)]; H NMR: d 7.36–7.23 (m, 5H), 3.80–3.74
(m, 2H), 3.67 (dd, J 10.9 and 7.1 Hz, 1H), 3.01 (dd, J 13.6
and 3.6 Hz, 1H), 2.90 (br s, 71H, OH), 2.66 (dd, J 13.6
and 9.5 Hz, 1H), 2.32 (br s, 1H), 1.81 (m, 1H), 1.01
(d, J 7 Hz, 3H).
3.2.12. (2S,3R) and (2S,3S)-2-Methyl-4-phenylbutane-
1,3-diol (11D12).32 An excess amount of Raney nickel
was added, under hydrogen atmosphere, to a solution of
the alcohol 5 (85 mg, 0.15 mmol) in ethanol (2 mL). The re-
action mixture was stirred at room temperature for 18 h, and
then filtered through a Celite pad, which was washed with
ethanol, and the solvent was evaporated. The residue was
1
(film): 3064, 2893, 1708, 1495 cmꢀ1; H NMR: 7.20–7.07
(m, 5H), 4.43 (dt, J 8.7 and 3.4 Hz, 1H), 2.80–2.69 (m,
2H), 2.61 (dd, J 13.4 and 8.8 Hz, 1H), 1.32–0.79 (m,
45H); 13C NMR: d 174.0, 139.4, 129.8, 128.1, 126.1, 75.0,
46.9, 39.9, 18.1, 18.0, 17.9, 12.7, 12.0; MS (FAB+) m/z
507 (8) [M+1]+, 463 (100) [MꢀCH(CH3)2]+, 277 (11),

´
J. L. Garcıa Ruano et al. / Tetrahedron 62 (2006) 12297–12305
12304
91 (6); HRMS [M+1]+: Calcd for C29H55O3Si2: 507.3689;
found, 507.3677.
´
(b) Garcıa Ruano, J. L.; Barros, D.; Maestro, M. C.; Alcudia,
ꢀ
A.; Fernandez, I. Tetrahedron: Asymmetry 1998, 9, 3445; (c)
Garcıa Ruano, J. L.; Barros, D.; Maestro, M. C.; Slawin,
´
A. M. Z.; Page, P. C. B. J. Org. Chem. 2000, 65, 6027.
13. For alkylation reaction see: (a) Girodier, L. D.; Rouessac, F. P.
Tetrahedron: Asymmetry 1994, 5, 1203; (b) Nakamura, S.;
Yasuda, H.; Watanabe, Y.; Toru, T. J. Org. Chem. 2000, 65,
8640; (c) Nakamura, S.; Oda, M.; Yasuda, H.; Toru, T.
3.2.16. [2R,3R]-3-Hydroxy-2-methyl-4-phenylbutanoic
acid (18).33 To a solution of 17 (0.04 mmol) in THF
(2.1 mL) was dropwise added hydrogen fluoride–pyridine
(0.47 mL) at 0 ꢁC. The mixture was stirred at room temper-
ature for 17 h, and then, diluted with ether (1 mL) and cooled
at 0 ꢁC before slowly adding a saturated aqueous sodium
hydrogencarbonate solution until CO2 evolution ceased.
The organic layer was discarded, and the aqueous one was
extracted with ether. The combined organic phases were
washed with saturated aqueous CuSO4 solution, water, and
brine. The organic layer was separated, dried (MgSO4),
and the solvent was removed under reduced pressure to
afford the acid as a yellow oil. Yield: 68% (1H NMR);
1H NMR: 7.37–7.21 (m, 5H), 3.93 (m, 1H), 2.95–2.59 (m,
3H), 1.32 (d, J 7.0 Hz, 3H).
´
Tetrahedron 2001, 57, 8469; (d) Almorın, A.; Carren˜o,
M. C.; Somoza, A.; Urbano, A. Tetrahedron Lett. 2003, 44,
5597.
14. For hetero Diels–Alder reaction see: Arai, Y.; Masuda, T.;
Masaki, Y.; Shiro, M. Tetrahedron: Asymmetry 1996, 7, 1199.
15. For allylation reaction see: (a) Arai, Y.; Masuda, T.; Masaki, Y.;
Koizumi, T. Heterocycles 1994, 38, 1751; (b) Arai, Y.; Suzuki,
A.; Masuda, T.; Masaki, Y.; Shiro, M. J. Chem. Soc., Perkin
Trans. 1 1995, 2913.
16. (a) Arai, Y.; Masuda, T.; Masaki, Y. Synlett 1997, 1459; (b)
Arai, Y.; Moneda, T.; Masuda, T.; Masaki, Y. Heterocycles
2000, 53, 1479.
Acknowledgements
´
17. (a) Garcıa Ruano, J. L.; Carren˜o, M. C.; Toledo, M. A.;
Aguirre, J. M.; Aranda, M. T.; Fischer, J. Angew. Chem., Int.
We thank the CICYT (Grant BQU2003-04012) for financial
ꢀ
support. M.A.F.-I. thanks Comunidad Autonoma de Madrid
for a predoctoral fellowship.
´
Ed. 2000, 39, 2736; (b) Garcıa Ruano, J. L.; Aleman, J.;
Soriano, J. F. Org. Lett. 2003, 5, 677; (c) Garcıa Ruano, J. L.;
ꢀ
´
ꢀ
´
Aleman, J. Org. Lett. 2003, 5, 4513; (d) Garcıa Ruano, J. L.;
Aranda, M. T.; Aguirre, J. M. Tetrahedron 2004, 60, 5383;
References and notes
´
(e) Garcıa Ruano, J. L.; Aleman, J.; Aranda, M. T.;
Fernandez-Iban˜ez, M. A.; Rodrıguez-Fernandez, M. M.;
ꢀ
ꢀ
ꢀ
´
ꢀ
´
Maestro, M. C. Tetrahedron 2004, 60, 10067; (f) Garcıa
Ruano, J. L.; Aranda, M. T.; Puente, M. Tetrahedron 2005,
1. (a) Modern Aldol Reactions; Mahrwald, R., Ed.; Wiley-VCH:
Weinheim, 2004; Vols. 1 and 2; (b) Heathcock, C. H.; Kim,
B. M.; Williams, S. F.; Masamune, S.; Rathke, M. W.;
Weipert, P.; Paterson, I.; Gennari, C. Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 2,
pp 133–319.
´
´
61, 10099; (g) Garcıa Ruano, J. L.; Martın-Castro, A. M.;
Tato, F.; Pastor, C. J. J. Org. Chem. 2005, 70, 7346; (h)
´
Garcıa Ruano, J. L.; Aleman, J.; Parra, A. J. Am. Chem. Soc.
2005, 127, 13048.
ꢀ
´
´
ꢀ
18. Garcıa Ruano, J. L.; Martın-Castro, A. M.; Tato, F.; Cardenas,
2. (a) Cowden, C. J.; Paterson, I. Organic Reactions; Paquette,
L. A., Ed.; Wiley: New York, NY, 1997; Vol. 51, Chapter 1;
(b) Mahrwald, R. Chem. Rev. 1999, 99, 1095; (c) Palomo, C.;
D. J. Tetrahedron: Asymmetry 2005, 16, 1963.
´
ꢀ
ꢀ
19. (a) Garcıa Ruano, J. L.; Fernandez-Iban˜ez, M. A.; Maestro,
´
Oiarbide, M.; Garcıa, J. M. Chem.—Eur. J. 2002, 8, 37; (d)
Palomo, C.; Oiarbide, M.; Garcıa, J. M. Chem. Soc. Rev.
2004, 33, 65.
´
ꢀ
M. C.; Rodrıguez-Fernandez, M. M. J. Org. Chem. 2005, 70,
´
´
1796; (b) Garcıa Ruano, J. L.; Fernandez-Ibanez, M. A.;
Maestro, M. C.; Rodriguez-Fernandez, M. M. Tetrahedron
ꢀ
ꢀ˜
ꢀ
3. (a) Mukaiyama, T.; Kobayashi, S.; Sano, T. Tetrahedron 1990,
46, 4653 and references to previous work; (b) Mukaiyama, T.
Tetrahedron 1999, 55, 8609.
2006, 62, 1245.
20. Evans, D. A.; Rovis, T.; Kozlowski, M. C.; Downey, W.;
Tedrow, J. S. J. Am. Chem. Soc. 2000, 122, 9134.
21. It is noteworthy that the use of propanenitrile as the solvent,
that would allow to lower the reaction temperature down to
ꢀ78 ꢁC, and therefore to attain a better diastereoisomeric ratio
in relation with that obtained with acetonitrile, was unsuccess-
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