Asymmetric synthesis of tertiary vinyl carbinols by highly stereoselective methylation of α-methyl-β-ketosulfoxides with aluminum reagents

Article abstract of DOI:10.1016/j.tet.2004.05.016

Methylation of chiral acyclic α-methyl-β-ketosulfoxides with Me₃Al and Me₂AlCl is reported. Induced configuration at hydroxylic carbon is mainly controlled by the configuration of the sulfinyl group, with de's higher than 90% in most of the cases regardless the configuration at C-α. The stereochemical pathway seems to be different with both reagents, thus affording a higher stereoselectivity with Me ₂AlCl. Pyrolytic desulfinylation and hydrogenolysis of the C-S bond allowed the transformation of the resulting hydroxysulfoxides into interesting optically pure tertiary methyl carbinols.

Full text of DOI:10.1016/j.tet.2004.05.016

Tetrahedron 60 (2004) 5701–5710
Asymmetric synthesis of tertiary vinyl carbinols by highly
stereoselective methylation of a-methyl-b-ketosulfoxides with
aluminum reagents
Jos e´ L. Garc ´ı a Ruano, M. Mercedes Rodrıguez-Fernandez and M. Carmen Maestro
*
*
´
´
Departamento de Qu ´ı mica Org a´ nica(C-I), Universidad Aut o´ noma, Cantoblanco, 28049 Madrid, Spain
Received 2 March 2004; revised 7 May 2004; accepted 10 May 2004
3 2
Abstract—Methylation of chiral acyclic a-methyl-b-ketosulfoxides with Me Al and Me AlCl is reported. Induced configuration at
hydroxylic carbon is mainly controlled by the configuration of the sulfinyl group, with de’s higher than 90% in most of the cases regardless
the configuration at C-a. The stereochemical pathway seems to be different with both reagents, thus affording a higher stereoselectivity with
Me AlCl. Pyrolytic desulfinylation and hydrogenolysis of the C–S bond allowed the transformation of the resulting hydroxysulfoxides into
2
interesting optically pure tertiary methyl carbinols.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Aluminum reagents have been widely used in organic
1
synthesis mainly due to their Lewis acidic features,
strongly dependent on the aluminum substituents. Their
2
well-known reactivity as alkylating agents has been used in
3
asymmetric synthesis in the presence of chiral catalysis or
4
,5
on substrates containing different chiral inductors. In this
context, the sulfinyl group has been used to control the
6
,7
stereoselectivity of the alkylations, our group pioneering
this field with the study of the reactions of Me Al with chiral
3
8
9
cyclic and a-unsubstituted acyclic b-ketosulfoxides
Scheme 1). Although acyclic substrates afforded hydroxy-
Scheme 1.
(
sulfoxides in good yields (90%) and high levels of
asymmetric induction (de’s .74%), their synthetic interest
was limited because methyl carbinols (trialkylaluminum
chiral compounds taking advantage of the reactivity of the
sulfinyl group.
reagents different to Me Al were not efficient) resulting
3
Herein we report the results obtained in the asymmetric
methylation of acyclic a-methyl-b-ketosulfoxides with
Me Al and Me AlCl, the rationalization of these results
3 2
from the desulfinylation processes would not be chiral
Scheme 1).
(
and some synthetic applicabilities of the resulting hydroxy-
sulfoxides based on the reactivity of the sulfinyl group.
In order to solve this problem in the case of acyclic
compounds, it was necessary the use of a-substituted
b-ketosulfoxides as the starting compounds. They would
yield hydroxysulfoxides containing two chiral carbons
which could be transformed into chiral tertiary carbinols
by hydrogenolysis of the C–S bond or used to prepare other
2. Results and discussion
The reactions of a-substituted b-ketosulfoxides with
1
0
DIBAL had shown to be highly stereoselective only
when they were conducted in the presence of ZnX2,
presumably due to the formation of a chelated species
activating the substrate. By contrast, a complete control of
the stereoselectivity was observed in reactions of
Keywords: Stereoselective ketone methylation; Trimethylaluminum;
Dimethylaluminum chloride; Chiral tertiary allylic alcohols;
Hydroxysulfoxides.
*
Corresponding authors. Fax: þ34-914973966 (J.L.G.R.);
e-mail addresses: joseluis.garcia.ruano@uam.es; carmen.maestro@uam.es
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.05.016

5702
J. L. Garc ´ı a Ruano et al. / Tetrahedron 60 (2004) 5701–5710
1
1
b-ketosulfoxides with Et AlCN regardless the presence of
2
and 2. The results obtained in the reactions of compounds 1
with Me Al/ZnX , as well as those conducted in toluene as
the solvent, were much less satisfactory (low conversions
and scarce stereoselectivity).
ZnX as the catalyst. Regarding the methylation reactions of
2
a-sulfinyl cycloalkanones with Me Al and Me Al/ZnX
2
(they are a-substituted b-ketosulfoxides) the stereo-
selectivity increased in the presence of ZnX , but the
3
2
8
3
3
2
reactivity was scarcely modified. On the contrary, only these
reactions of R-CO–CH –SOTol with Me Al/ZnBr took
On the basis of the exceptionally high chelating power of
2
1
Me AlCl with b-heterosubstituted carbonyl compounds,
2
2
3
2
9
place satisfactorily. With these antecedents, we initiated
the study of the methylation reactions with Me Al. We
that strongly increases their reactivity, we decided to
evaluate the ability of this reagent as a methylating agent.
It has been used as a catalyst to promote important reactions
3
chose a-methyl b-ketosulfoxides 1–4 (Scheme 2), contain-
ing aryl and alkyl groups, as the substrates, in order to
evaluate the influence of the nature and size of R on the
stereoselectivity.
1
2a,13
14
such as Diels–Alder cycloadditions,
ene reactions,
12b,15
conjugated additions, additions to the carbonyl group,
5
1
6
17
amide formation, and formation of aluminium enolates,
but only in a few cases it simultaneously acted as a
nucleophile on the activated substrate.
2
a,c,18
The reactions of ketosulfoxides 1–4 with AlMe Cl were
2
performed at room temperature in toluene or CH Cl as the
2
2
solvent. In Table 2 are indicated the diastereomeric ratios of
0
0
the obtained carbinols A, A , B, B (Scheme 3), that were
determined by HPLC from the reaction crudes obtained
under different conditions. We first studied the behavior of
the mixture 1aþ1b (R¼n-Pr), that was used to evaluate the
influence of different factors on the stereoselectivity and
yield of the reactions. The order of the addition of the
Scheme 2.
The synthesis of the starting sulfoxides 1–4 (R-CO–
CHMe–SOTol) was accomplished following a previously
described procedure by reaction of (R)-(þ)-ethyl p-tolyl
sulfoxide with the corresponding esters RCO Et in the
reagents (substrate must be added onto the AlMe
important to attain higher conversions (compare entries 4
and 5) and the number of equivalents of AlMe Cl was also
2
Cl) was
2
1
1b
presence of LDA
(Scheme 2). These reactions yielded
40:60 mixtures of the two possible epimers (a and b) at
,
2
C-a. Only t-butyl derivatives 4a and 4b could be separated
by flash chromatography and therefore isolated as pure
diastereoisomers. Hence, mixtures of a:b epimers of
compounds 1–3 were used as the starting materials in
methylation reactions.
determinant. Reactions must be performed in the presence
of a high excess of the reagent (3 or 4 equiv.), because with
lower reagent proportion (2.2 equiv.) the reaction rate
sharply decreased and a significant amount of starting
ketosulfoxide was recovered (compare entries 8 and 9 with
6
and 7, respectively).
The reactions of compounds 1–4 with Me Al (4 equiv.) in
3
CH Cl under similar conditions (rt, 30 min) to those
2
Concerning the stereoselectivity, the results show that the
evolution of the epimer 1b was highly stereoselective under
all the studied conditions (de , 87–90%) whereas 1a
evolved with only moderated stereoselectivity (de , 30–
50%). This situation was scarcely modified by any change in
the solvent and the temperature. These factors have some
influence on the reaction rate, which was slightly lower in
2
8
,9
previously reported
Table 1. Starting from 1 and 3, mixtures of the four possible
afforded the results collected in
0
from a epimers whereas B and B derive from the b ones, see
stereoisomers of the corresponding adducts (A and A derive
0
Scheme 3) were obtained. By contrast, the evolution of 2a
and 2b was completely stereoselective and only two
stereoisomers (A and B) were obtained from the starting
mixture. Reactivity of the t-butyl derivatives was lower and
CH Cl than in toluene (compare entries 1 and 4 with 2 and
2 2
6, respectively) and decreased as the temperature became
lower. Moreover the epimerization extent was much more
significant in toluene and also when the temperature
decreased (see Table 2). As the configuration at hydroxyl-
4
b needed 5 h (instead of 30 min required by 1–3) at room
temperature to evolve, with moderate yield, into 8B in a
completely stereoselective way. Compound 4a was even
less reactive and required 25 h to be transformed into a
0
0
ated carbon is R for A and B and S for A and B (see
Scheme 3), the best conditions from a stereoselective point
of view are those optimized with 3 equiv. at 0 8C (at lower
0
70:30 mixture of diastereoisomers 8A and 8A . A higher
reactivity was also detected for b isomers of compounds 1
Table 1. Methylation of compounds 1–4 with AlMe
3
a
0
0
Substrate (a:b ratio)
Reagent
Product ratio A:A : B:B
Yield (%)
Recovered substrate % (a:b)
b
1
2
3
4
4
(39:61)
(36:64)
(44:56)
a
b
AlMe
AlMe
AlMe
AlMe
AlMe
3
3
3
3
3
13:10 : 67:10
c
72
58
89
40
43
13 (44:56)
20 (81:19)
—
—
—
29:0 : 71:0
33:10 : 38:19
c
d
e
c
70:30 : 0:0
c
0:0 : 100:0
a
b
c
d
e
3 2 2
Reactions conditions: rt, 30 min and 4 equiv. of Me Al in CH Cl .
Determined by HPLC (column: Zorbax RX-C8; eluent: MeOH: CH
1
Determined by H NMR.
Reaction time: 25 h.
Reaction time: 5 h.
3
CN:H
2
O 37:13:50; 1.4 mL/min).

J. L. Garc ´ı a Ruano et al. / Tetrahedron 60 (2004) 5701–5710
5703
Scheme 3.
Table 2. Reaction of compounds 1–4 with Me
2
AlCl
T (equiv)
a,b
Products A:A : B:B
0
0
Entry
Substrate (a:b ratio)
Yield (%)
Recovered substrate % (a:b)
c
1
2
3
4
5
6
7
8
9
1a,b (39:61)
1a,b (38:62)
1a,b (38:62)
1a,b (40:60)
rt (4)
rt (4)
0 8C (4)
25:13 : 57:5
11:5 : 80:4
6:2 : 86:6
18:9 : 69:4
26:10 : 61:3
11:5 : 80:4
6:3 : 86:5
76
83
68
90
68
88
67
60
48
98
73
—
22(20:80)
c
rt (3)
rt (3)
rt (3)
d
1a,b (39:61)
—
—
23(26:74)
28(34:66)
46(52:48)
—
14(100:0)
—
42(100:0)
100
100
1a,b (38:62)
1a,b (38:62)
1a,b (38:62)
1a,b (38:62)
2a,b (36:64)
3a,b (44:56)
3a,b (44:56)
3a,b (44:56)
4a
0 8C (3)
rt (2.2)
0 8C (2.2)
rt (3)
10:4 : 82:4
23:9 : 57:11
e
10
11
12
13
14
15
35:0 : 65:0
21 : 2 : 77:0
23:3 : 74:0
12:0 : 88:0
—
rt (3)
f
g
rt (3)
0 8C (3)
77
h
53
—
—
i
rt (3)
rt (3)
4b
—
a
b
c
d
e
f
Reaction conditions: 30 min in toluene.
Diastereomeric ratio measured by HPLC (columm: Zorbax RX-C8; eluent: MeOH–CH
Solvent: CH Cl
3
CN–H
2
O 37:13:50; 1.4 mL/min).
2
2
.
The reagent was added over the substrate.
Reaction time: 43 h.
Reaction time: 3 h.
g
h
i
0
After separation of 7A .
Reaction time: 10 h.
Reaction time: 60 h.
temperatures the reactions are quite slow) or room
temperature in toluene (those of the entries 6 and 7),
which yielded the higher AþB/A þB ratios.
methylated under similar reaction conditions although the
reaction times were increased (entries 14 and 15).
0
0
2.1. Configurational assignment
Under these conditions the results obtained for compounds
2
epimers were quantitatively transformed into the alcohols
after 30 min at room temperature with a complete control of
the stereoselectivity (entry 10). Under the same conditions
aþ2b and 3aþ3b were even better. In the first case, both
The assignment of the absolute configurations of the
obtained a-methyl-b-hydroxysulfoxides was based on the
following facts:
3
was completely stereoselective) and a 14% of the epimer a
aþ3b gave a mixture of three alcohols (the evolution of 3b
(a) The configuration (RS RC-a) had been previously
assigned to ketosulfoxides a and the (R SC-a
)
The complete
S
1
1b
was recovered, which indicates a slightly lower reactivity
(
configuration to the epimers b.
entry 11). A complete conversion was observed after 3 h
and a 77% of the mixture 7Aþ7B could be isolated upon
stereoselectivity observed in reactions of 2a, 2b, and
3b suggests that epimers A and B derive of the starting
ketosulfoxides a and b, respectively. Therefore, a and
b must exhibit the same configuration at sulfur and C-a
than A and B, respectively.
0
separation of 7A by chromatography (entry 12). Better
stereoselectivity was obtained when the reaction was
performed at 0 8C (entry 13), but the reaction is quite
slow, and a 42% of the epimer A was recovered. By
contrast, none of the t-butyl derivatives 4a or 4b, could be
(b) The oxidation of a 46:54 mixture of phenyl derivatives
7A and 7B afforded a mixture of diastereomeric

5704
J. L. Garc ´ı a Ruano et al. / Tetrahedron 60 (2004) 5701–5710
Scheme 4.
sulfones 9A and 9B (Scheme 4) in the same ratio than
that of the starting sulfoxides. It indicates that these
sulfones only differ in the configuration of one of their
two chiral carbons. As a consequence, the configur-
ation of the hydroxylated carbons must be identical for
epimers A and epimers B (they exhibit different
configuration at C-a).
(
c) The hydroxylic proton of compound 6A exhibits a
4
long range coupling constant ( J¼1.6 Hz) with the
methinic proton of the i-Pr group. As this is only
possible for hydroxylic protons involved in intra-
molecular hydrogen bonding exhibiting a W
coplanar arrangement with respect to the coupled
1
9
protons, the configuration of 6A at the hydroxylic
carbon must be R (Fig. 1).
Figure 2. X-ray structure for compound 6A.
Figure 1. Stereochemistry of the presumably most stable conformation for
compound 6A.
0
established in the case of hydroxysulfoxides 5A and 5B .
The configuration of the B isomers was unequivocally
0
According to these facts, we can assign the [R R RC–OH
S
]
Once isolated from their mixtures, they were independently
oxidized with MCPBA at room temperature, affording the
corresponding hydroxysulfones 10A and 10B (Scheme 4),
C-a
configuration to epimers A and the [RS SC-a RC–OH
configuration to the epimers B. The X-ray diffraction
]
0
2
0
analysis of 6A (Fig. 2) and of a racemic sample of 7B
which are enantiomers (they have identical spectroscopical
properties). The same conclusions could be deduced for
support this assignment. The conformation exhibited by 6A
in solid state is identical to that shown in Figure 1, deduced
from the NMR data.
0
compounds of the reaction mixtures, 5B and 5A, exhibit the
compounds 5A and 5B. By assuming that the major

J. L. Garc ´ı a Ruano et al. / Tetrahedron 60 (2004) 5701–5710
Table 3. Significant NMR parameters for configurational assignment of compounds 5–7
5705
0
0
0
0
Product
5A
6A
7A
8A
5A
7A
8A
5B
6B
7B
8B
5B
a
OH
d
d
5.53
10.30
5.41
9.90
6.11
10.90
5.42
12.50
5.23
10.40
6.50
—
5.21
12.30
2.69
4.00
3.16
3.50
3.96
4.80
—
5.21
2.68
4.60
a
a-Me
a
Values of d expressed in ppm.
same configuration than those obtained as sole products in
reactions from 2aþ2b and 3aþ3b, we can assign the
stereochemistry of the conformations shown in Figure 3 for
A and B epimers.
configurations [R R
S
S
] and [R S
S
S
] to the
C-a C–OH
C-a C–OH
0
quently to all A and B isomers).
0
minor compounds 5A and 5B , respectively (and conse-
0
0
3. Mechanistic proposal
In Table 3 are indicated the significant NMR parameters
0
The main differences observed in the reactions with Me Al
3
and Me AlCl are related to reactivity and stereoselectivity.
2
0
which are clearly different for epimers A (A ) and B (B ).
The Me Al is able to react with t-butyl derivatives (4b
3
required 5 h and 4a more than 1 day), whereas Me AlCl did
2
not react. The stereoselectivity was not identical but the
epimer obtained as the major one with both reagents was the
same (compare Tables 1 with 2).
The d values for the hydroxylic protons are clearly different
[
0
ones]. That suggests that A epimers exhibit intramolecular
0
.5 ppm for isomers A (A ) but ,4 ppm for the B (B )
2
1
hydrogen bonds whereas this is not the case for the B
1
3
epimers. On the other hand, the C-d value ca. 10 ppm
observed for the CH –CH carbon in compounds B (B ) is
quite different to the ca. 4 ppm observed for epimers A (A ).
0
3
According to the evolution proposed by Evans in reactions
12
0
with Me AlCl, our b-ketosulfoxides (epimers a and b)
2
This strong difference, which is indicative of a substantial
modification in the shielding patterns of both compounds,
could also be a consequence of the formation of hydrogen
bonds. In Figure 3 are indicated the presumably most stable
conformations of the different isomers able to explain the
observed differences in the NMR parameters. Epimers B
must be transformed into complexes I and I by chelation of
a
b
the aluminum to both oxygen atoms of the substrate with
elimination of the chloride anion, which is captured by a
second Me AlCl molecule. A third molecule of the reagent
2
must be therefore necessary to introduce the methyl group
into the carbonyl moiety. It would explain that 3 equiv. of
Me AlCl were required to achieve a high conversion
0
2
0
and B must be stabilized by the n !d interaction between
the lone electron pair at oxygen and the empty d orbital at
sulfur, which has shown to be even more important than the
2
(
Fig. 4). On the basis of the higher stability of the half-
chair structure of the chelate species and taking into account
the tendency of the p-tolyl group (with higher size than the
methyl one) to adopt the pseudoequatorial arrangement, we
can propose I and I (Fig. 4) as the presumably most stable
2
2
hydrogen bond in many b-hydroxysulfoxides. By con-
trast, A and A isomers exhibit their predominant rotamers
0
stabilized by intramolecular hydrogen bonding, because the
a
b
2
0
conformation containing the n !d interaction would be
highly unstable due to the (Tol/Me) or (Tol/R) 1,3-parallel
interaction. Taking into account the significant deshielding
effect produced by the lone electron pair at sulfur on the
conformations resulting from the chelation of the epimers a
and b. The approach of the reagent from the upper face
(chair-like TS) would be favored with respect to the attack
to the bottom face (twist-like TS) from a steric point of
view. Moreover, the stabilizing interaction of the metal with
the lone electron pair at sulfur makes even more favorable
the approach to the upper face. According to this analysis,
k1.k2 and k .k , this would explain why hydroxy-
2
3
carbon atoms adopting an antiperiplanar arrangement,
3
the C-d values shown in Table 3 are consistent with the
1
3
4
sulfoxides A and B were obtained as major isomers from
epimers a and b, respectively. Additionally, k .k and
k .k , due to the steric hindrance of the methyl group at
3
1
2
4
C-a in both epimers. It would explain the higher stereo-
selectivity observed in the evolution of the b epimers.
Finally, the complete stereoselectivity observed in reaction
0
from 2a (R and R ¼Me in I ) is not unexpected on the basis
a
of the steric hindrance of the approach of the reagent to the
bottom face exerted by R (see Fig. 4).
0
The stereochemical course of the reactions with Me Al must
3
be similar. The factors controlling the preferences for the
attack of the reagent to pentacoordinated aluminum species
2
4
formed from Me Al (Fig. 5) are the same indicated for the
3
tetracoordinated species generated from Me AlCl (Fig. 4).
2
The only difference is the presumable lower stability of the
pentacoordinated species, which would explain the less
stereoselective evolution observed in reactions with Me Al
Figure 3. Favored conformations for the different isomers.
3

5706
J. L. Garc ´ı a Ruano et al. / Tetrahedron 60 (2004) 5701–5710
2
Figure 4. Stereochemical pathway of the reaction with Me AlCl.
3
Figure 5. Stereochemical pathway of the reaction with Me Al.
(other nor chelated species could also evolve) as well as
their higher reactivity.
4
. Synthetic applications
The obtained hydroxysulfoxides can be used as starting
molecules to prepare different enantiomerically pure
compounds taking advantage of the reactivity of the sulfinyl
group. As the configuration at the hydroxylated carbon is the
same for epimers A and B (obtained as the major ones or
even unique in these reactions), all the transformations
involving the removal of the sulfur function can be
performed by using a mixture of these epimers, with no
previous separation. We have illustrated these possibilities
with two of these reactions, hydrogenolysis of the C–S bond
and pyrolytic desulfinylation, starting from the mixture
Scheme 5.
reaction with Raney Ni (Scheme 5) for 1 day at room
temperature (shorter reaction times revealed the presence
of the thioether derived from 7) afforded compound 11 in
65% yield with high optical purity (ee 96%). Otherwise,
when the mixture 7Aþ7B was heated with refluxing xylene
in the presence of NaHCO , compound 12 (ee 96% by
3
chiral HPLC) was obtained in 85% yield (Scheme 5). These
results illustrate the usefulness of our method for the
preparation of enantiomerically pure tertiary vinyl
carbinols, which are not easily synthesized by other
2
procedures.
2
5
2
6
7Aþ7B (Scheme 5). This mixture was obtained in 77%
yield by chromatographic separation from the reaction
mixture obtained from 3aþ3b (entry 12 of Table 2). Its
2
7
6b,28

J. L. Garc ´ı a Ruano et al. / Tetrahedron 60 (2004) 5701–5710
5707
5. Conclusion
layer was dried (MgSO ) and evaporated. The residue was
4
purified by chromatography (the eluent was indicated in
each case).
The highly stereoselective methylation of acyclic a-methyl
b-ketosulfoxides can be performed with Me AlCl. Result-
2
ing hydroxysulfoxides can be used in the synthesis of
tertiary methyl vinyl and methyl ethyl carbinols in very high
optical purities.
6.3. General procedure for Me AlCl addition. Method B
2
A solution of b-ketosulfoxide (0.30 mmol) in anhydrous
toluene (1.5 mL) was dropwise added into a solution of
dimethyl aluminum chloride in anhydrous toluene (1.0 M,
0.90 mL, 0.90 mmol) under argon, and the mixture was
stirred for 30 min at room temperature. Then the mixture
was cooled to 0 8C and methanol (0.60 mL) was slowly
added. When the mixture reached room temperature, it was
treated with 10 mL of aqueous saturated solution of sodium
potassium tartrate–ethyl acetate (1:1) and then stirred for
30 min. The aqueous layer was extracted with ethyl acetate
6
. Experimental
6
.1. General
Dry solvents and liquid reagents were distilled under argon
just prior to use: THF and toluene were distilled from
sodium and benzophenone ketyl; DIA was dried over
sodium hydroxide and distilled over calcium hydride;
CH Cl was dried over P O and stored over molecular
(3£10 mL) and the organic layer was dried (MgSO
) and
4
evaporated. The residue was purified by column chroma-
tography on silica gel (the eluent was indicated in each
case).
2
2
2 5
sieves. All reaction vessels were flame-dried and flushed
with argon. TLC was performed on silica gel F254 plates
with silica gel G (Merck), spots being developed with
phosphomolybdic acid in ethanol. Silica gel Merck 60
6.3.1. 3-Methyl-2-p-tolylsulfinylhexan-3-ol (5). The treat-
ment of a 38:62 mixture of 1aþ1b following the method B
afforded a diastereoisomeric mixture of hydroxysulfoxides
(
230–400 mesh) was used for flash chromatography.
Optical rotations were measured with a 241 Perkin–Elmer
polarimeter at room temperature (20–23 8C) in the solvent
and concentration indicated in each case (concentration in
g/100 mL). Melting points were determined in a
Gallenkamp MFB-595 apparatus in open capillary tubes
0
0
5A, 5A , 5B, and 5B as a colorless oil. The mixture was
purified by chromatography (hexane–ethyl acetate 4:1) and
0
0
yielded pure (5A and 5B) and enriched (5A and 5B )
hydroxysulfoxides.
1
13
and are uncorrected. H NMR (300 MHz, CDCl ) and
C
NMR (75.5 MHz CDCl ) spectra were performed with a
3
6.3.2. Compound [(2R,3R,(S)R)]5A. It was obtained as a
1
3
Bruker AC-300 spectrometer. Chemical shifts are given in
ppm (d), relative to SiMe as the internal reference; signal
colorless oil. Yield: 2%; [a]
NMR: d 7.65 and 7.33 (AA BB system, 4H, C
D
¼þ181 (c 5.6, chloroform). H
0
0
H
), 5.53
4
6
4
multiplicities are quoted as s, singlet; d, doublet; dd, double
doublet; dq, double quartet; t, triplet; q, quartet; and m,
multiplet. J Values are given in hertz. Mass spectra were
recorded by the direct insertion technique by electronic
impact (EI) at 70 eV or FAB using a VG AutoSpec
spectrometer. Elemental analyses were obtained with a
Perkin–Elmer 2400 CHNS/O series II. X-ray diffractions
were collected with a Siemens P4RA difractometer. Starting
ketosulfoxides 1–4 were synthesized and purified according
(bs, 1H, OH), 2.97 (q, 1H, J¼7.3 Hz, CHS), 2.42 (s, 3H,
CH
CH
Ar), 1.54 (s, 3H, CH
COH), 1.53–1.19 (m, 4H,
), 0.88 (t, 3H, J¼7.1 Hz, CH CH ), 0.83 (d, 3H,
CH). C NMR: d 142.8, 139.4, 129.9, 126.1,
3
2
3
CH
2
3
2
1
3
J¼7.3 Hz, CH
3
75.6, 66.5, 44.2, 23.2, 21.5, 15.6, 14.4, 10.3. MS: (m/z)(%):
254 (Mþ,,1), 239 (84), 221 (11), 149 (36), 140 (100), 139
(32), 115 (20), 92 (31), 91 (21), 83 (22), 71 (36), 57 (29), 55
(31). HRMS: calcd for C14
254.1340.
H
22SO 254.1331; found
2
1
1b
to the previously described procedure.
Dimethyl
0
from a 55:45 mixture of 5A and 5A . H NMR: d 7.65 and
aluminum chloride (1.0 M solution in hexanes) and
trimethylaluminum (1.0 M solution in heptane) was
purchased from Aldrich. Yields and diastereisomeric ratios
6.3.3. Compound [(2R,3S,(S)R)]5A . It was characterized
1
0
0
0
7.33 (AA BB system, 4H, C
(q, 1H, J¼7.1 Hz, CHS), 2.42 (s, 3H, CH
(m, 4H, CH CH ), 1.18 (s, 3H, CH COH), 1.00 (t, 3H,
CH C
H
6 4
), 5.23 (bs, 1H, OH), 2.97
1
of alcohols were established by integration ( H NMR) of
3
Ar), 2.02–1.70
well-separated signals of the diastereisomers in the crude
reaction mixtures and/or by HPLC. Yields and diastereo-
isomeric ratios of hydroxysulfoxides 5–8 are listed in
Tables 1 and 2.
2
2
3
1
3
J¼7.1 Hz, CH
), 0.89 (d, 3H, J¼7.1 Hz, CH
CH).
3
2
3
NMR: d 142.8, 139.5, 129.9, 126.1, 76.1, 69.1, 38.7, 26.4,
23.2, 16.5, 14.6, 10.4.
6
.2. General procedure for AlMe addition. Method A
3
6.3.4. Compound [(2S,3R,(S)R)]5B. It was obtained as a
white solid (mp 156–159 8C). Yield: 32%. [a] ¼þ139 (c
D
1
0
0
A solution of b-ketosulfoxide (0.283 mmol) in anhydrous
toluene (1.3 mL) was dropwise added into a solution of
trimethylaluminum (1.132 mmol) in anhydrous toluene
2.4, chloroform). H NMR: d 7.40 and 7.32 (AA BB
system, 4H, C
J¼7.2 Hz, CHS), 2.42 (s, 3H, CH
CH ), 1.55 (s, 3H, CH COH), 1.52–1.25 (m, 2H, CH
(d, 3H, J¼7.2 Hz, CH CH), 0.97 (t, 3H, J¼7.5 Hz,
). C NMR: d 140.7, 139.0, 129.7, 124.0, 74.5,
H
6 4
), 2.69 (bs, 1H, OH), 2.51 (q, 1H,
Ar), 1.77–1.65 (m, 2H,
), 1.02
3
(
1.3 mL) under argon, and the mixture was stirred for
2
3
2
3
0
0 min at room temperature. Then the mixture was cooled to
8C and methanol (0.55 mL) was slowly added. When the
3
1
3
CH CH
3 2
mixture reached room temperature, it was treated with 9 mL
of aqueous saturated solution of sodium potassium tartrate–
ethyl acetate (1:1) and stirred for 30 min. The aqueous layer
was extracted with ethyl acetate (3£6 mL) and the organic
67.7, 42.3, 25.9, 21.3, 16.8, 14.5, 4.0. IR (KBr): 3360, 1022.
MS (FABþ): 255 (Mþ1)(100), 239 (77), 49 (56), 139 (62),
97 (82), 91 (22), 71 (36), 57 (47), 54 (54). HRMS (MþH):
calcd for C14H22SO 255.141; found 255.1426.
2

5708
J. L. Garc ´ı a Ruano et al. / Tetrahedron 60 (2004) 5701–5710
0
from a mixture of 5B and 5B . H NMR: d 7.40 and 7.32
6
.3.5. Compound [(2S,3S,(S)R)]5B . It was characterized
6.3.11. Compound [(2R,3S,(S)R)]7B. It was obtained as a
white solid (mp 101–103 8C). Yield: 31%; [a] ¼þ144 (c
0
AA BB system, 4H, C H ), 2.69 (bs, 1H, OH), 2.51 (q, 1H,
1
D
0
0
1
(
6.8, chloroform). H NMR: d 7.47 and 7.22 (m, 9H,
aromatic protons), 3.96 (bs, 1H, OH), 2.76 (q, 1H, J¼
6
4
J¼7.2 Hz, CHS), 2.42 (s, 3H, CH Ar), 1.77–1.65 (m, 2H,
3
CH ), 1.55 (s, 3H, CH COH), 1.52–1.25 (m, 2H, CH ), 1.02
2
6.9 Hz, CHS), 2.36 (s, 3H, CH Ar), 2.00 (s, 3H, CH COH),
3
2
3
3
1
3
(
CH CH ). C NMR: d 140.6, 139.5, 129.9, 124.2, 74.6,
d, 3H, J¼7.2 Hz, CH CH), 0.97 (t, 3H, J¼7.5 Hz,
0.74 (d, 3H, J¼6.9 Hz, CH CH). C NMR: d 146.1, 141.1,
3
3
1
3
137.8, 129.8, 128.2, 126.9, 124.6, 124.1, 76.4, 66.7, 29.9,
21.3, 4.8. MS (m/z)(%): 151 (10), 148 (62), 140 (100), 139
3
2
6
8.1, 43.8, 24.7, 23.7, 16.8, 14.5, 4.6.
(17), 105 (21), 92 (43), 91 (39), 79 (15), 77 (23), 71 (13).
Anal. calcd for C H SO : C, 70.80; H, 6.99; S, 11.12.
Found: C, 70.61; H, 6.79; S, 11.00.
6
.3.6. 3,4-Dimethyl-2-p-tolylsulfinylpentan-3-ol (6). The
1
7
20
2
treatment of a 36:64 mixture of 2aþ2b following the
method B afforded a diastereoisomeric mixture of hydroxy-
sulfoxides 6A and 6B as a colorless oil. The mixture was
purified by chromatography (hexane–ethyl acetate 2:1) to
yield pure hydroxysulfoxide 6A and enriched 6B
hydroxysulfoxides.
6.3.12. 3,4,4-Trimethyl-2-p-tolylsulfinylpentan-3-ol (8).
Starting from 4a, method A afforded a diastereoisomeric
mixture of hydroxysulfoxides 8A and 8A . The mixture was
0
purified by chromatography (hexane–ethyl acetate 2:1) to
0
yield pure hydroxysulfoxides 8A and 8A as a white solids.
6
.3.7. Compound [(2R,3R,(S)R)]6A. It was obtained as a
Starting from 4b, hydroxysulfoxide 8B was exclusively
obtained. The product was purified by chromatography
(hexane–ethyl acetate 2:1) to afford pure 8B as a white
solid.
white solid (mp 77–79 8C). Yield: 35%; [a] ¼þ179.4 (c
D
1
0
0
9
.1, chloroform). H NMR: d 7.68 and 7.35 (AA BB
system, 4H, C H ), 5.41 (d, 1H, J¼1.6 Hz, OH), 3.04 (q,
6
4
1
H, J¼7.2 Hz, CHS), 2.43 (s, 3H, CH Ar), 1.67 (m, 1H,
3
CH(CH ) ), 1.54 (s, 3H, CH COH), 1.00 (d, 3H, J¼6.9 Hz,
6.3.13. Compound [(2R,3R,(S)R)]8A. It was obtained as a
white solid (mp 88–91 8C). Yield: 27%; [a] ¼þ141.9 (c
3
2
3
CH CHCH ), 0.89 (d, 3H, J¼6.9 Hz, CH CHCH ), 0.83 (d,
3
3
3
3
D
1
3
1
0
0
3
1
H, J¼7.2 Hz, CH CH). C NMR: d 142.8, 139.3, 129.9,
1.69, chloroform). H NMR: d 7.68 and 7.38 (AA BB
3
26.2, 76.7, 66.2, 35.5, 21.5, 21.4, 16.2, 16.1, 9.9. IR
system, 4H, C H ), 5.42 (s 1H, OH), 3.21 (q, 1H, J¼7.2 Hz,
CHS), 2.43 (s, 3H, CH Ar), 1.46 (s, 3H, CH COH), 1.00 (s,
3 3
6
4
þ
(KBr): 3335, 2993, 1083. MS: (m/z)(%): 254 (M ,,1), 221
(15), 151 (20), 140 (100), 139 (49), 115 (22), 97 (13), 92
(49), 91 (29), 71 (57), 55 (31). Anal. calcd for C H SO :
1
3
9H, (CH ) C), 0.94 (d, 3H, J¼7.2 Hz, CH CH). C NMR:
3
3
3
d 142.6, 139.4, 129.9, 126.7, 78.9, 66.7, 39.9, 25.8, 21.5,
18.7, 12.5.
1
4
22
2
C, 66.34; H, 8.69; S, 12.51. Found: C, 66.10; H, 8.72; S,
1
2.61.
0
6
.3.14. Compound [(2R,3S,(S)R)]8A . It was obtained as a
6
from a mixture of 6A and 6B. Yield: 65%. H NMR: d 7.39
.3.8. Compound [2S,3R,(S)R)]6B. It was characterized
1
white solid (mp 88–91 8C). Yield: 13%; [a] ¼þ168.2 (c
D
1
0
0
0.65, chloroform). H NMR: d 7.67 and 7.34 (AA BB
0
0
and 7.29 (AA BB system, 4H, C H ), 3.16 (bs, 1H, OH),
6
system, 4H, C H ), 5.21 (s 1H, OH), 3.12 (q, 1H, J¼7.5 Hz,
CHS), 2.43 (s, 3H, CH Ar), 1.33 (s, 3H, CH COH), 1.21 (s,
3 3
4
6 4
2
.58 (q, 1H, J¼6.9 Hz, CHS), 2.39 (s, 3H, CH Ar), 2.03
3
1
3
(
1
sep, 1H, J¼6.9 Hz, CH(CH ) ), 1.52 (s, 3H, CH COH),
9H, (CH ) C), 0.97 (d, 3H, J¼7.5 Hz, CH CH). C NMR:
3
2
3
3 3
3
.01 (d, 3H, J¼6.9 Hz, CH CHCH ), 0.99 (d, 3H,
d 142.6, 140.2, 129.9, 126.1, 80.9, 69.8, 40.1, 27.7, 26.2,
21.5, 12.3.
3
3
J¼6.9 Hz, CH CHCH ), 0.81 (d, 3H, J¼6.9 Hz, CH CH).
3
3
3
1
3
C NMR: d 140.8, 138.5, 129.8, 124.0, 76.5, 65.0, 34.8,
1.3, 20.8, 17.4, 16.3, 3.5. IR (KBr): 3480, 2950, 1500,
380, 1010. MS (FAB): 255 (Mþ1, 100), 155 (13), 154
2
1
6.3.15. Compound [(2S,3R,(S)R)]8B. It was obtained as a
white solid (mp 123–125 8C). Yield: 43%. [a] ¼þ124.5
D
1
0
0
(
38), 139 (55), 135 (50), 115 (21), 97 (71), 91 (31), 72 (91),
(c0.6, chloroform). H NMR: d 7.44 and 7.31 (AA BB
7
C H SO 255.1419; found 255.1420.
1 (49), 69 (33), 57 (36), 54 (49). HRMS (MþH): calcd for
system, 4H, C H ), 2.88 (q, 1H, J¼6.9 Hz, CHS), 2.42 (s,
6
4
3H, CH Ar), 1.57 (s, 3H, CH COH), 1.11 (d, 3H, J¼6.9 Hz,
3 3
1
4
22
2
1
3
CH CH), 1.13 (s, 9H, (CH ) C). C NMR: d 140.6, 140.1,
3
3 3
6
.3.9. 2-Phenyl-3-p-tolylsulfinylbutan-2-ol (7). The treat-
129.7, 124.1, 76.6, 65.4, 39.4, 26.4, 21.7, 21.3, 5.21. Anal.
calcd for C H SO : C, 67.12; H, 9.01; S, 11.95. Found: C,
66.95; H, 8.80; S, 11.81.
ment of a 44:56 mixture of 3aþ3b following the method B
1
5
24
2
afforded a diastereoisomeric mixture of hydroxysulfoxides
7A and 7B as a colorless oil. The mixture was purified by
flash chromatography (hexane–ethyl acetate 3:1) yielding
pure 7B and enriched 7A.
6.4. Sulfinyl group oxidation
A CDCl3 solution of the corresponding hydroxy-
sulfoxides was added to an NMR tube containing an
excess of previously dried (anhydrous magnesium
sulfate) MCPBA solution in the same solvent. The
sulfone ratios and NMR signals were obtained from the
crude mixtures.
6
.3.10. Compound [(2R,3R,(S)R)]7A. It was characterized
from a 52:48 mixture of 7A and 7B. [a] ¼þ58 (c 1.8,
D
1
chloroform). H NMR: d 7.64 and 7.16 (m, 9H, aromatic
protons), 6.11 (bs, 1H, OH), 3.02 (q, 1H, J¼7.1 Hz, CHS),
2
.35 (s, 3H, CH Ar), 1.95 (s, 3H, CH COH), 0.55 (d, 3H,
3 3
1
3
J¼7.2 Hz, CH CH). C NMR: d 145.2, 141.0, 139.2, 129.9,
3
1
28.0, 127.4, 125.9, 124.6, 76.3, 68.6, 22.1, 21.4, 10.9. IR
6.4.1. 2-Phenyl-3-p-tolylsulfonylbutan-2-ol (9). Hydroxy-
sulfone 9 was prepared as a 46:54 diastereoisomeric mixture
of 9A and 9B by MCPBA oxidation of a 46:54 mixture of
7A and 7B, respectively.
(
(
(
KBr): 3480, 2950, 1500, 1380, 1010. MS: (m/z)(%): 151
14), 148 (72), 140 (100), 139 (17), 105 (27), 92 (49), 91
42), 79 (17), 77 (26), 71 (16).

J. L. Garc ´ı a Ruano et al. / Tetrahedron 60 (2004) 5701–5710
5709
1
6
9
(
.4.2. Compound (2R,3R)9A. H NMR: d 8.10–7.31 (m,
H, aromatic protons), 3.42 (q, 1H, J¼7.1 Hz, CHS), 2.38
Acknowledgements
s, 3H, CH Ar), 1.88 (s, 3H, CH COH), 0.88 (d, 3H,
3
We thank the CICYT (BQU2003-04012) for financial
support.
3
J¼7.1 Hz, CH CH).
3
1
6
9
(
.4.3. Compound (2R,3S)9B. H NMR: d 8.10–7.31 (m,
H, aromatic protons), 3.38 (q, 1H, J¼7.2 Hz, CHS), 2.37
s, 3H, CH Ar), 1.82 (s, 3H, CH COH), 0.98 (d, 3H,
3
References and notes
3
J¼7.2 Hz, CH CH).
3
1
. Negishi, E. Organometallics in Organic Synthesis; Wiley:
New York, 1980.
6
.4.4. (2R,3R) and (2S,3S)-3-Methyl-2-p-tolylsulfonyl-
hexan-3-ol (10A) and (10B ). The MCPBA oxidation
0
of hydroxysulfoxide 5A yielded hydroxysulfone 10A.
2. (a) Ashby, E. C.; Noding, S. A. J. Org. Chem. 1979, 44, 4792.
(b) Snider, B. B.; Rodini, D. J.; Karras, M.; Kirk, T. C.;
Deutsch, E. A.; Cordova, R.; Price, R. T. Tetrahedron 1981,
37, 3927. (c) R u¨ ck, K.; Kunz, H. Synthesis 1993, 1018. (d)
Taniguchi, M.; Fujii, H.; Oshima, K.; Utimoto, K. Tetrahedron
Lett. 1992, 33, 4353. (e) Garc ´ı a Ruano, J. L.; Tito, A.;
Culebras, R. Tetrahedron 1996, 52, 2177.
0
1
0B (enantiomer of 10A) was obtained by oxidation
1
0
0
0
of 5B . H NMR: d 8.10–7.31 (AA BB system, 4H,
C H ), 3.20 (q, 1H, J¼7.1 Hz, CHS), 2.48 (s, 3H,
6
4
CH Ar), 1.55 (s, 3H, CH COH), 1.51–1.20 (m, 4H,
3
3
CH CH ), 1.21 (d, 3H, J¼7.1 Hz, CH CH), 0.9 (t, 3H,
2
2
3
J¼7.0 Hz(CH CH ).
3. For addition of R Al to aldehydes see: (a) Pagenkopf, B. L.;
3
3
2
Carreira, E. M. Tetrahedron Lett. 1998, 39, 9593. (b) Lu, J.-F.;
6.4.5. (2R,3S) and (2S,3R)-3-Methyl-2-p-tolylsulfonyl-
hexan-3-ol (10A ) and (10B). The MCPBA oxidation of
You, J.-S.; Gau, H.-M. Tetrahedron: Asymmetry 2000, 11,
2531. (c) You, J.-S.; Hsieh, S.-H.; Gau, H.-M. Chem.
Commun. 2001, 1546.
0
hydroxysulfoxide 5A yielded hydroxysulfone 10A . 10B
0
enantiomer of 10A ) was obtained by oxidation of 5B. H
0
0
NMR: d 8.10–7.30 (AA BB system, 4H, C H ), 3.25 (q,
1
(
4. Ley, S. V.; Cox, L. R.; Meek, G.; Metten, K.-H.; Piqu e´ , C.;
Worrall, J. M. J. Chem. Soc., Perkin Trans. 1 1997, 3299.
5. (a) Castellino, S.; Dwight, W. J. J. Am. Chem. Soc. 1993, 115,
2986. (b) Amoroso, R.; Cardillo, G.; Sabatino, P.; Tomasini,
C.; Trer e` , A. J. Org. Chem. 1993, 58, 5615.
0
0
6
4
1
4
H, J¼7.2 Hz, CHS), 2.46 (s, 3H, CH Ar), 2.0–1.41 (m,
3
H, CH CH ), 1.30 (s, 3H, CH COH), 1.20 (d, 3H,
3
2
2
J¼7.2 Hz, CH CH), 0.95 (t, 3H, J¼7.0 Hz(CH CH ).
3
3
2
6
. Fujisawa, T.; Fujimura, A.; Ukaji, Y. Chem. Lett. 1988, 1541.
6
.5. Sulfinyl group reductive elimination
7. Recent references: (a) Carre n˜ o, M. C.; P e´ rez Gonz a´ lez, M.;
Ribagorda, M.; Houk, K. N. J. Org. Chem. 1998, 63, 3687. (b)
Almor ´ı n, A.; Carre n˜ o, M. C.; Somoza, A.; Urbano, A.
Tetrahedron Lett. 2003, 44, 5597.
6.5.1. (S)-2-Phenyl-2-butanol (11). To a solution of a 27:73
mixture of 7A and 7B (0.59 mmol) in EtOH was added a
suspension of activated Raney nickel (1.726 g) in EtOH
(
temperature, filtered over Celite , and the residue was
purified by chromatography (hexane–ethyl acetate 99:1) to
8. (a) Bueno, A. B.; Carre n˜ o, M. C.; Fischer, J.; Garc ´ı a Ruano,
J. L.; Pe n˜ a, B.; Pe n˜ as, L.; Rubio, A. Tetrahedron Lett. 1991,
32, 3191. (b) Bueno, A. B.; Carre n˜ o, M. C.; Garc ´ı a Ruano, J. L.
An. Qu ´ı m. 1994, 90, 442.
4 mL). The reaction was stirred for 1 day at room
w
give a colorless oil. Yield: 65%. [a] ¼216.6 (c 3.5,
9. Carre n˜ o, M. C.; Garc ´ı a Ruano, J. L.; Maestro, M. C.; P e´ rez
Gonz a´ lez, M.; Bueno, A. B.; Fischer, J. Tetrahedron 1993, 49,
11009.
D
2
5a
acetone). [Lit. [a] ¼216.7 (c 1.50, acetone, 96% ee)].
D
1
H NMR: d 7.26–7.19 (m, 5H, C H ), 1.86 (q, 2H,
5
6
J¼7.5 Hz, CH CH ), 1.79 (s, 1H, OH), 1.55 (s, 3H,
10. Barros, D.; Carre n˜ o, M. C.; Garc ´ı a Ruano, J. L.; Maestro, M. C.
Tetrahedron Lett. 1992, 33, 2733.
3
2
CH COH), 0.80 (t, 3H, J¼7.5 Hz, CH CH ).
3
3
2
1
1. (a) Garc ´ı a Ruano, J. L.; Mart ´ı n Castro, A. M.; Rodriguez, J. H.
Recent Res. Devel. Org. Chem. 2000, 4, 261. (b) Garc ´ı a
Ruano, J. L.; Mart ´ı n Castro, A. M.; Rodriguez, J. H. J. Org.
Chem. 1992, 57, 7235.
6
.6. Sulfinyl group pyrolysis
6
.6.1. (S)-2-Phenylbut-3-en-2-ol (12). A 25 mL two-
necked round bottomed flask equipped with a stirrer and a
reflux condenser and containing sodium bicarbonate
12. (a) Evans, D. A.; Chapman, K. T.; Bisaha, J. J. Am. Chem. Soc.
1988, 110, 1238. (b) Evans, D. A.; Allison, B. D.; Yang, M. G.;
Masse, C. E. J. Am. Chem. Soc. 2001, 123, 10840.
(
13.1 mmol), was flame-dried under Ar steam. A solution
of a 27:73 of 7A and 7B (0.328 mmol) in o-xylene (6 mL)
was added via cannula and was heated at 140 8C for 14 h.
The reaction was filtered over Celite and washed with
dichlorometane. Dichlorometane was eliminated under
reduced pressure without heating, in order to avoid
evaporation of any reaction product. Flash chromatography
using successively hexane (to remove the remaining o-
xilene) and then hexane–ethyl acetate 9:1, yielded pure 12
N-acyloxazolidinone-nEt AlCl complexes have been
2
established by NMR. See Ref. 5(a).
13. Marshall, J. A.; Audia, J. E.; Grote, J.; Shearer, B. G.
Tetrahedron 1986, 42, 2893.
w
14. (a) Snider, B. B.; Zhang, Q. J. Org. Chem. 1991, 56, 4908.
(b) Houston, T. A.; Tanaka, Y.; Koreeda, M. J. Org. Chem.
1993, 58, 4287. (c) Masuya, K.; Tanino, K.; Kuwajima, I.
Tetrahedron Lett. 1994, 35, 7965.
2
6
(
ee was determined by HPLC (Daicel CHIRALPAK AD,
85%) as an oil [a] ¼228.3 (c 2.1, acetone, 96% ee). The
15. (a) Nakamura, S.; Yasuda, H.; Watanabe, Y.; Toru, T. Org.
Chem. 2000, 65, 8640. (b) Ooi, T.; Morikawa, J.; Uraguchi, D.;
Maruoka, K. Tetrahedron Lett. 1999, 40, 2993.
D
1
Hexane/ i-PrOH: 90/10, 0.8 mL/min). H NMR: d 7.51–
.24 (m, 5H, C H ), 6.19 (dd, 1H, J¼17.2, 10.8 Hz,
7
16. Shimizu, T.; Osako, K.; Nakata, T. Tetrahedron Lett. 1997, 38,
2685.
17. (a) Maruoka, K.; Hashimoto, S.; Kitagawa, Y.; Yamamoto, H.;
6
5
CHvCH ), 5.22 (dd, 2H, J¼17.2, 1.1 Hz, CHvCH ),
2
2
1
.67 (s, 3H, CH COH).
3

5710
J. L. Garc ´ı a Ruano et al. / Tetrahedron 60 (2004) 5701–5710
Nozaki, H. J. Am. Chem. Soc. 1977, 99, 7705. (b) Takahashi,
25. (a) Garc ´ı a, C.; La Rochelle, L. K.; Walsh, P. J. J. Am. Chem.
Soc. 2002, 124, 10970. (b) Archelas, A.; Furstoss, R. J. Org.
Chem. 1999, 64, 6112. (c) Johnson, C.; Stark, C. J., Jr. J. Org.
Chem. 1982, 47, 1193. (d) Weber, B.; Seebach, D.
Tetrahedron 1994, 50, 6117.
A.; Shibasaki, M. J. Org. Chem. 1988, 53, 1227. (c) van der
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1
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