The search for tolerant Lewis acid catalysts. Part 2: Enantiopure cycloalkyldialkylsilyl triflimide catalysts

Article abstract of DOI:10.1016/j.tet.2007.05.086

A series of 2-aryl- and arylmethyl-3-dialkylphenylsilyl cycloalkanones have been prepared and resolved. The pure enantiomers were reduced to the corresponding cycloalkane derivatives. These were used for the in situ generation of enantiopure cycloalkylsil

Full text of DOI:10.1016/j.tet.2007.05.086

Tetrahedron 63 (2007) 8449–8462
The search for tolerant Lewis acid catalysts. Part 2:
Enantiopure cycloalkyldialkylsilyl triflimide catalysts
a
a
c
a,d,
Zilong Tang,a,b Benoit Mathieu, Bernard Tinant, Georges Dive and Leon Ghosez
*
ꢀ
a
´
Department of Chemistry, Universite catholique de Louvain, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium
bSchool of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, PR China
c
´
Centre d’ingenierie des proteines, Institut de chimie B6, Universite de Liege, 13, allee du 6 aout Sart-Tilman, 4000 Liege, Belgium
´
´
ꢁ
´
ˆ
ꢁ
d
´
Institut Europeen de Chimie et Biologie (IECB) rue Robert Escarpit, 2, F-33607 Pessac, France
Received 15 April 2007; accepted 22 May 2007
Available online 26 May 2007
Abstract—A series of 2-aryl- and arylmethyl-3-dialkylphenylsilyl cycloalkanones have been prepared and resolved. The pure enantiomers
were reduced to the corresponding cycloalkane derivatives. These were used for the in situ generation of enantiopure cycloalkylsilyl trifli-
mides by protodesilylation with bis(trifluoromethanesulfonyl)imide. The association of a bulky leaving group with a silicon atom carrying
large substituents was again shown to favour the complexation of silicon with carbonyl groups: all these trialkylsilyl triflimides showed
a high catalytic activity for Diels–Alder reactions. Enantiomeric excesses up to 59% were observed. This is the highest enantioselectivity
ever observed for a Diels–Alder reaction catalysed by a silicon Lewis acid.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
generated in situ, was an efficient catalyst for many carbon–
carbon bond-forming reactions,8 or, e.g., the acid-catalysed
ring-opening polymerisation of cyclosiloxanes.9
In the course of our studies on enantioselective Diels–Alder
reactions of activated azadienes,1 we found that many metal-
based chiral Lewis acid catalysts could not be used as a result
of competitive bindings to the diene and the dienophile car-
bonyl group. In the case of 2-azadienes a solution was found,
which uses the bidentate imide group and the Box copper(II)
catalyst developed by Evans and Johnson.2 However, this
approach was totally unsuccessful for 1-azadiene cycloaddi-
tions.3 Another solution for efficient catalysis of 2-azadienes
cycloadditions was the use of a more basic activating group
of the dienophilic double bond in conjunction with silyltri-
flates as Lewis acid catalysts: a,b-unsaturated amides were
shown to react smoothly with 2-azadienes in the presence
of TBDMSOTf.4 However, silyltriflates were not acidic
enough to activate the corresponding esters. In 1997, both
our group and Mikami’s group discovered that N-(trimethyl-
silyl)triflimide (Me3SiNTf2) was an extremely efficient
carbonyl activator.5,6 We observed an unexpected reversal
Stimulated by these successful results, we decided to exam-
ine the possibility of generating chiral silyl triflimides,
which could act as Lewis acids for the activation of carbonyl
groups. The possibility of using an asymmetric silicon atom
was rejected since these compounds are not readily accessi-
ble and steric course of substitution at silicon is complex. At
the outcome of these studies, no such catalyst had been
described. Examples of Diels–Alder reactions catalysed by
an enantiopure silicon catalyst were described in 1998 but
facial selectivities were very modest (eeꢀ10%).10 More
recently Leighton et al. have reported the first examples
of highly enantioselective carbon–carbon bond-forming
reactions catalysed by silyl chlorides derived from enan-
tiopure aminoalcohols.11 At this point, however, the scope
and limitations of this elegant approach have not yet been
defined.
€
of thermodynamic acidity on going from the Bronsted
acids (HOTf>HNTf2) to the TMS derivatives (TMSOTf<
TMSNTf2), which was assigned to the larger size of the tri-
flimide group as compared to triflate.5 Also our group dem-
onstrated that increasing the size of the alkyl substituents
on silicon resulted in a significant increase of Lewis acidity.7
It was later shown by several groups that TMSNTf2, often
Our approach was inspired by the successful studies of chiral
boron Lewis acid catalysts by Hawkins’ group.12 We first
prepared several silylated triflimides derived from (ꢁ)-
myrtenal and tested them as catalysts of the Diels–Alder
reactions of methyl acrylate and methyl crotonate to cyclo-
pentadiene (Scheme 1).7 The best ee was z54%. We now
wish to report the details of our studies of a variety of
a-aryl- or arylmethyl-cycloalkylsilyl triflimides as catalysts
for the asymmetric Diels–Alder reactions of a,b-unsaturated
esters.
Keywords: Lewis acid; Enantioselective catalysis; Asymmetric Diels–Alder
cycloadditions; Silylated triflimides.
* Corresponding author. E-mail: ghosez@chim.ucl.ac.be
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.086

8450
Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
Table 1. a-Arylation of epoxyketones 1a–c
R
R
NTf2
SMe2Ph
SiMe2
Ar
R
n
Yield, % (lit.)
65 (64)
HNTf2
CH2Cl2
2a
2b
2c
2d
2e
2f
H
1
catalysts
H
1
1
1
1
1
54 (62)
15
CO2Me
10% of catalyst
CH2Cl2
+
CO2Me
H
major enantiomer
Scheme 1. Silylated triflimides derived from (ꢁ)-myrtenal. For R¼OMe at
ꢁ78 ꢂC, yield¼83%, ee¼54%.
H
34 (30)
31a
OMe
OPh
H
2. Synthesis of the enantiopure scaffolds
2.1. Synthesis of trans-2-aryl-3-dialkylphenylsilyl cyclo-
alkanones
Me
46
2,3-Epoxyketones are versatile building blocks in organic
synthesis.13 They have been shown to behave as versatile
equivalents of a-ketovinyl cations.14 Compounds 1a–c
were prepared by epoxidation of the cyclic enones with hy-
drogen peroxide under basic conditions following literature
procedures15 (Scheme 2).
2g
H
0
50b
prepared from Ph2O.16
a
PhO
Li
Yields not mentioned in literature.17
b
O
O
O
Ar
54-76%
a, b
O
( )
n
( )
( )
R
n
n
O
O
O
R
R
R
R
R
Ar
Ar
SiR'2Ph
Ar
a, b,c
+
( )
R
( )
R
( )
2a-g
1a-c
n
n
n
SiR'2Ph
R
R
R R
Scheme 2. Reagents and conditions: (a) LDA (1.1 equiv) in THF, ꢁ78 ꢂC;
(b) ArLi (2 equiv), ꢁ23 ꢂC then PTSA (cat) in refluxing toluene.
2a-g
3a-h
4a-h
Scheme 3. Reagents and conditions: (a) PhMe2SiCl or PhEt2SiCl (3 equiv),
Li (9 equiv), THF; (b) addition of PhR02SiLi in suspension of CuCN
(1.5 equiv), ꢁ30 ꢂC then 0 ꢂC; (c) 2a–g (1 equiv), THF, ꢁ23 ꢂC/rt then
quench.
a-Aryl enones 2a–g were prepared following Wender’s
general procedure14d (Scheme 2, Table 1). Prior formation
of an enolate by treatment of 1a–c with LDA was essential
to ensure the chemo- and regioselective opening of the
epoxide ring by the aryl lithium reagent.
and from 11.1 to 13.0 Hz for the trans-isomers.20 As shown
later, the structure and configuration of 3f was confirmed by
X-ray diffraction analysis.
The reaction of CuCN with dimethyl- or diethylphenyl-
silyllithium generated the corresponding cuprate reagents,
which were reacted with enones 2a–g according to
Fleming’s procedure (Scheme 3, Table 2).18 The reactions
were quenched by methanol at room temperature: these
conditions only gave the trans-adduct 3a–h as predicted
on the basis of the early observations of the group of
Seyden-Penne.19 The trans-stereoselectivity was probably
the result of a thermodynamically controlled protonation
occurring at higher temperature and in more basic
conditions.19 Indeed, quench with a saturated NH4Cl
solution at 0 ꢂC mainly gave mixtures of stereoisomers
(cis-4>trans-3) except when n¼0 and Ar¼1-Np (only
trans).
Table 2. Michael additions of phenyldialkylsilyl cuprate reagents to 2-aryl-
cycloalkenones
Method of quenchinga
n
R
R0 Ar
Yield,b
3 (trans) 4 (cis)
%
a
a
b
c
c
d
e
f
A
B
A
B
A
B
B
B
A
B
1
1
1
1
1
1
1
1
0
1
H
H
H
H
H
H
H
Me Ph
Me Ph
Me 1-Np
Me 9-An
Me 9-An
3
71
34
20
—
70
—
23
—
15
—
—
—
—
—
Me 2-PhOMe 67
Me 2-PhOPh 57
Me Me 1-Np
H
H
50
73
70
Figure 1 shows the typical 1H and 13C NMR patterns and as-
signments for a cis-adduct 4a. The cis- and trans-isomers
were distinguished by the values of coupling constants
JH ꢁH , which varied from 5.1 to 5.7 Hz for the cis-isomers
g
h
Me 1-Np
Et Ph
a
A: aqueous NH4Cl, 0 ꢂC; B: MeOH, rt.
Yields of isolated products.
b
2
3

Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
8451
1.75 (1H), 32.50 ppm
Table 3. Tandem 1,4-addition–alkylation of cyclohexenone and cyclopent-
enone
JH3-H4 = 13.6 Hz
Ar
n
Yields
of 5, %
Yields
of 6, %
Jw = 2 Hz
JH2-H3 = 5.7 Hz
H
H3
0.04 (1H), -4.15 ppm
0.06 (1H), -3.98 ppm
H
a
b
c
Ph
2-Np
1-Np
1
1
1
85
41
39
9
4
7
H
Si Ph
H
1
H2
H4
Ph
O
H
3.66 (1H), 58.17 ppm
211.46 ppm
Figure 1. Typical 1H and 13C NMR patterns for a cis Michael adduct 4a.
2.2. Synthesis of trans-2-arylmethyl-3-dimethylphenyl-
silyl-cyclohexanones 5
A series of trans-2-arylmethyl-3-silyl cycloalkanones 5a–c
were prepared by tandem reactions involving the 1,4-addi-
tion of silyl cuprate to cyclohexenone followed by reaction
of the in situ generated enolates with arylmethyl bromides
(Scheme 4, Table 3).21 In all cases we obtained the pure
trans-2-arylmethyl-3-silyl cycloalkanones 5 after column
chromatography. In most cases, small amounts of diaryl-
methylated products 6 were also formed. However, we were
not able to avoid the formation of 6 without significantly
lowering the yield of 5. In all cases the reactions were highly
trans-stereoselective.
Figure 2. ORTEP drawing of compound (ꢁ)-3f.
2.3. Resolution of the racemic cycloalkanones
Racemic ketones 3a–h and 5a–c were resolved by prepar-
ative HPLC. Chiralcell AD or OD-H columns gave excel-
lent separation of these enantiomeric ketones. Enantiomers
eluting first showed negative optical rotations while the
isomers with longer retention times showed positive optical
rotations. The absolute configurations of enantiomerically
pure trans-cycloalkanone (ꢁ)-3f was shown to be (2R,3S)
by X-ray diffraction analysis (Fig. 2) while (+)-5a and
(+)-5b were shown to be the (2S,3S) configurations (Figs. 3
and 4).22 The absolute configuration of other trans-
cycloalkanones could be inferred from the above results:
the enantiomeric ketones with positive optical rotations
were assigned absolute configuration (2S,3S) and those
with negative optical rotations were assigned configuration
(2R,3R).
Figure 3. ORTEP drawing of compound (+)-5a.
2.4. Synthesis of ENP 2-dialkylphenylsilyl-aryl
(arylmethyl)-cycloalkanes
of syn and anti isomers. Reduction of the crude hydrazone
with NaBH3CN/ZnCl2 (2:1) yielded the corresponding
cycloalkane (Scheme 5, Table 4).23 Yields were moderate
to good except for the reduction of the tosylhydrazone
derived from ketone 3c, which gave a complex mixture of
products.
The carbonyl group of enantiomerically pure (ENP) cyclo-
alkanones was reduced following the experimental protocol
described by Kim et al.23 The ketone was first converted into
the corresponding tosylhydrazone. The crude tosylhydr-
azones showed two spots on TLC suggesting the presence
OCu
O
O
O
a
b
Ar
Ar
Ar
+
( )
( )
n
SiMe2Ph
n
( )
( )
n
SiMe2Ph
n
SiMe2Ph
5
6
Scheme 4. Reagents and conditions: (a) PhMe2SiLi (3 equiv), CuI (1.5 equiv), in THF/HMPA, ꢁ30 ꢂC then addition of enone (1 equiv) at ꢁ78 ꢂC/ꢁ23 ꢂC;
(b) arylmethyl bromide (2.8 equiv), ꢁ78 ꢂC then aqueous NH4Cl at 0 ꢂC.

8452
Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
Figure 4. ORTEP drawing of compound (+)-5b.
O
S
S
Ar
Ar
TsN
Ar
b
a
O
Ar
N
Ar
Ar
( )
( )
m
m
( )
m
SiMe2Ph
SiMe2Ph
SiMe2Ph
b
a
( )
( )
n
n
( )
n
SiR'2Ph
SiR'2Ph
SiR'2Ph
R
R
R
R
Ar = Ph
(-)
(+) 4a
4a
(+) 10a
(-) 10a
(+) 10b
(-) 10b
(+) 9a
R
R
(-) 9a
(+) 9b
(-) 9b
3a-h, 5a-c
(and enantiomers)
7a-h, 8a-c
Ar = 1-Np (+) 4b
(-) 4b
crude
(and enantiomers)
Scheme 6. Reagents and conditions: (a) ketone (1 equiv), ethanedithiol
(1.2 equiv), TiCl4 (0.3 equiv) in CH2Cl2, ꢁ40 ꢂC/rt; (b) 10a or 10b
(1 equiv), Ra–Ni (10 equiv) in CH3OH, rt.
Scheme 5. Reagents and conditions: (a) TsNHNH2 (1.2 equiv), EtOH,
60 ꢂC, 3–6 h; (b) NaBH3CN (5 equiv), ZnCl2 (2.5 equiv), EtOH/MeOH
(1:1), 60 ꢂC, 3–10 h.
When applied to the cis-isomers 4a, this method gave a
mixture of cis- and trans-1,2-disubstituted cycloalkanes:
epimerisation probably occurred during the formation of
the tosylhydrazone. We then turned to an alternative
reductive method involving the formation of a dithioketal
followed by a desulfurisation reaction with Raney nickel
(Scheme 6).24,25
3. Synthesis of the ENP silylated triflimides
In an earlier paper in this series, we showed that TMSNTf2
could be quantitatively generated by protodesilylation
of the corresponding phenyltrimethylsilane.18c,26 We have
applied this method for the preparation of the new ENP
catalysts (Scheme 7). The transformation of phenylsilanes
into the corresponding silylated triflimides was monitored
by 1H NMR. The signals of the protons of the methyl groups
connected to the silicon atom moved downfield (from 0.20
to 0.60 ppm) and a signal appeared at 7.36 ppm for the pro-
tons of benzene. When silicon carries two ethyl groups, the
protodesilylation reaction became very slow at room tem-
perature (w10% conversion after 3 h in CH2Cl2) but was
quantitative at 80 ꢂC in toluene (Scheme 8).
Table 4. Reduction of ENP 3-silylated cycloalkanones
Ketone
n
m
R
R0
Ar
Product
Yield,a
%
(+)-3a
(ꢁ)-3a
(+)-3b
(ꢁ)-3b
(+)-3c
(+)-3d
(ꢁ)-3d
(+)-3e
(ꢁ)-3e
(+)-3f
(ꢁ)-3f
(+)-3g
(ꢁ)-3g
(+)-3h
(ꢁ)-3h
(+)-5a
(ꢁ)-5a
(+)-5b
(ꢁ)-5b
(+)-5c
(ꢁ)-5c
1
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
H
H
H
H
H
H
H
H
H
Me
Me
H
H
H
H
H
H
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Ph
Ph
(ꢁ)-7a
(+)-7a
(+)-7b
(ꢁ)-7b
31
44
45
39
1-Np
1-Np
9-An
2-PhOMe
2-PhOMe
2-PhOPh
2-PhOPh
1-Np
1-Np
1-Np
1-Np
Ph
Ph
Ph
Ph
2-Np
2-Np
1-Np
1-Np
Complex mixture
HNTf2
+
C6H6
R-SiMe2Ph
R-SiMe2NTf2
(ꢁ)-7d
51
57
20
25
31
27
32
32
31
35
54
85
34
38
31
33
CH2Cl2, rt
(+)-7d
(+)-7e
(ꢁ)-7e
(+)-7f
rac, (+), (-)-7a,b,e,f,g
rac, (+), (-)-8a-c
rac, (+), (-)-11a,b,e,f,g
rac, (+), (-)-12a-c
(ꢁ)-7f
(+)-7g
(ꢁ)-7g
(ꢁ)-7h
(+)-7h
(+)-8a
(ꢁ)-8a
(+)-8b
(ꢁ)-8b
(+)-8c
(ꢁ)-8c
Scheme 7. General procedure for the generation of phenyldialkylsilyltrifl-
imide catalysts.
Et
Ph
Ph
Me
Me
Me
Me
Me
Me
HNTf2
SiEt2Ph
SiEt2NTf2
rac, (+), (-)-7h
rac, (+), (-)-11h
Scheme 8. Reagents and conditions: CH2Cl2, rt, 3 h, yield¼10% or toluene,
80 ꢂC, 3 h,w100%.
a
Yields based on ketone for the two-step sequence.

Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
8453
substituent followed by an irreversible demethylation reac-
tion (Scheme 9).
HNTf2 in CH2Cl2
0 °C or -30 °C
OMe
OMe
SiMe2Ph
SiMe2NTf2
4. Evaluation of the ENP silylated triflimides as catalysts
for the Diels–Alder reaction
(-)-7d
(-)-11d
We selected the cycloaddition of cyclopentadiene to methyl
acrylate as model reaction. This should allow an easy com-
parison with the studies of Hawkins’ group on related boron
catalysts.12
NTf2
O
CH3NTf2
+
O
Me
Si
Si
Me2
Me2
The catalysts (10 mol %) were formed in the solvent
(CH2Cl2 in most cases) of the Diels–Alder reaction (Scheme
10). Then 20 mol % 2,6-di-tert-butyl-4-methylpyridine
13
Scheme 9.
€
(DTBMP) was added to neutralise any residual Bronsted
HNTf2. Methyl acrylate (1 equiv) and then cyclopentadiene
(4 equiv) were added at ꢁ78 ꢂC (or ꢁ100 ꢂC) and the mix-
ture was left at that temperature. The results are summarised
in Table 5.
The protodesilylation of (ꢁ)-3d did not give the expected
triflimide 11d but a cyclic siloxane 13, which probably
resulted from an intramolecular silylation of the methoxy
Table 5. ENP silylated triflimides as catalysts for the cycloaddition of methyl acrylate and cyclopentadiene
SM
Catalyst X¼NTf2
Conditions
Yield, %
endo/exo
ee, %
47
Product
configuration
Ph
(ꢁ)-7a
ꢁ78 ꢂC, CH2Cl2
95
32
2R
SiMe2X
1-Np
ꢁ78 ꢂC, CH2Cl2
ꢁ78 ꢂC, toluene
ꢁ100 ꢂC, CH2Cl2
96
95
94
>100
>100
>100
50
44
59
2R
2R
2R
(ꢁ)-7b
(ꢁ)-7e
(+)-7f
SiMe2X
PhO
ꢁ78 ꢂC, CH2Cl2
ꢁ78 ꢂC, CH2Cl2
80
95
19
49
35
40
2S
2S
SiMe2X
1-Np
SiMe2X
1-Np
(+)-7g
(ꢁ)-7g
ꢁ78 ꢂC, CH2Cl2
ꢁ100 ꢂC, CH2Cl2
95
95
99
32
49
56
2S
SiMe2X
1-Np
2R
SiMe2X
Ph
(ꢁ)-7h
ꢁ78 ꢂC, toluene
99
99
36
2R
SiEt2X
Ph
(ꢁ)-8a
(ꢁ)-8b
(ꢁ)-8c
ꢁ78 ꢂC, CH2Cl2
ꢁ78 ꢂC, CH2Cl2
ꢁ78 ꢂC, CH2Cl2
95
94
95
99
16
49
0
3
7
—
—
2S
SiMe2X
2-Np
SiMe2X
1-Np
SiMe2X
Ph
(ꢁ)-9a
(+)-9b
ꢁ78 ꢂC, CH2Cl2
ꢁ78 ꢂC, CH2Cl2
80
90
7.4
49
42
45
2S
2S
SiMe2X
1-Nap
SiMe2X

8454
Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
HNTf2
R*R'2SiPh +
silicon Lewis acid. The selectivity was higher for catalysts
having a 1-naphthyl group directly attached to the cyclo-
alkane ring. Insertion of a methylene group allowing for
more conformational mobility resulted in a significant
decrease of facial selectivity. cis-Catalysts gave lower ee
than the corresponding trans-catalysts. The presence of
a phenoxy group on the phenyl substituent did not raise
the selectivity in spite of a possible chelation of the oxygen
with silicon.
a
CO2Me
R*R'2SiNTf2
+
+
b
CO2Me
endo (2R)
CO2Me
endo (2S)
Scheme 10. Reagents and conditions: (a) 0.1 equiv of triflimides catalyst
generated in situ at rt or 70–80 ꢂC; (b) addition of methyl acrylate (1 equiv),
cyclopentadiene (4 equiv), DTMB (0.2 equiv), ꢁ78 ꢂC or ꢁ100 ꢂC.
An interesting observation was that catalyst derived from
(ꢁ)-7a and (ꢁ)-7b led to the same enantiomer although
they have opposite configurations. This suggested different
transition state structures in going from the phenyl to the
naphthyl-substituted catalysts. The selectivity observed
with the 1-naphthyl-substituted catalyst can be rationalised
on the basis of a an approach of the reactants similar to
that of the corresponding boron-catalysed reaction (Scheme
12):12a (1) both naphthalene and silyl groups are equatorial,
(2) silicon complexes the carbonyl group anti to the C–O
ester bond, (3) the configuration of the enone unit is
s-trans.27 This approach is favoured by electrostatic and
dipole-induced attractions between the complexed car-
bonyl group and the polarisable naphthalene substituent.
Thus the naphthalene substituent blocks the a-face of the
dienophile.
The first conclusions of these experiments were that
these chiral silyl triflimides were extremely active catalysts
for the Diels–Alder reaction. In most cases, reactions
were almost quantitative in less than 2 h. This had already
been demonstrated for the structurally more simple
TMS and TIPSNTf2, which have been shown to be much
better catalysts than the corresponding triflates. This can
be assigned to a relief of I-strain in going from the
trialkylsilyltriflimide to the corresponding silylated carbonyl
complex (Scheme 11).
k
OMe
R*R'2Si
O
NTf2
+
R*R'2SiX
OMe
O
KNTf2 KOTf
These attractive forces should be weaker when naphthyl
(17.6 D) is replaced by the less polarisable phenyl group
(10.4 D).12b Lower energy conformations of the methyl
methacrylate/(ꢁ)-11a complex were calculated to be
0.477 kcal/mol apart (Fig. 5).28
>
Scheme 11.
All reactions were highly endo-selective. Enantiomeric
excesses were measured by GC (CHIRASIL-DEX CB col-
umn) for the endo isomers only. The best enantiomeric
excesses was 59%, which is the highest enantioselectivity
ever observed for a Diels–Alder reaction catalysed by a
In the most stable conformation A (Fig. 5), the silicon atom
coordinates to the carbonyl group syn to the methoxy group
of a s-cis enone. In this conformation, the reactive double
O
OMe
+
(1R, 2S)
+
+
+
+
+
+
H
NTf2
H
Si
O
Si
Si
H
H
NTf2
O
O
O
O
NTf2
O
R
R
CO2Me
CO2Me
MeO2C
S
Scheme 12. Possible transition states for the catalysed cycloadditions.

Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
8455
Figure 5. Low energy conformations of methyl acrylate/(ꢁ)-11a complex.
bond is far away from the aryl group. Conformation B is only
0.477 kcal higher than A. It differs from A by the conforma-
tion around the olefin–ester bond, which brings the reactive
double bond closer to the aryl group. Therefore we have to
consider two additional transition states TS-2 and TS-3
(Scheme 12) leading to adducts of opposite configurations.
We are conscious that this analysis is still pretty rough but
it should help the design of new catalysts of this class, which
should have structural features favouring one TS over the
others. The replacement of the cyclohexane ring by a deca-
line would be an interesting possibility.
8.07 mL (5.83 g, 57.59 mmol) diisopropylamine in 140 mL
dry THF under argon. The mixture was stirred for 30 min
and then cooled to ꢁ78 ꢂC. Then, 5.87 g (52.35 mmol) 2,3-
epoxycyclohexanone was added slowly. The mixture was
stirred for another 30 min at this temperature.
To a solution of 14.56 mL (21.68 g, 104.7 mmol) 1-bromo-
naphthalene in 140 mL THF in a three-neck 500 mL flask,
123.18 mL (1.7 M, 81.30 g, 209.4 mmol) t-BuLi in pentane
was added at ꢁ78 ꢂC under argon. The reaction mixture was
stirred for 1 h at ꢁ78 ꢂC, then 10 min at 0 ꢂC. The resulting
mixture was then transformed to the above enolate solution
through a cannula at ꢁ78 ꢂC under the pressure of argon.
After this transformation was completed, the mixture was
stirred at ꢁ23 ꢂC for 2 h and 50 mL saturated NH4Cl was
added at 0 ꢂC. The mixture was extracted with 3ꢃ100 mL
Et2O. The organic layers were washed with 2ꢃ100 mL
3 N HCl, then 120 mL saturated NaHCO3 solution. The
collected organic phases were dried, filtered and evaporated
in vacuum.
5. Experimental
5.1. General
All reactions requiring anhydrous or inert conditions were
carried out under an atmosphere of dried argon in flame-
dried glassware. All solvents were dried by standard proce-
dure and freshly distilled. Infrared spectra were recorded on
a BIORAD FTS 135 FTIR. 1H NMR spectra were recorded
in CDCl3 on Varian Gemini-200, 300 or on Bruker AM-500
spectrometers at 200, 300 or 500 MHz. 13C NMR spectra
were recorded at 50, 75 or 125 MHz. Chemical shifts (d)
The above resulting crude product was placed into a 500 mL
flask with a Dean–Stark to separate the water. Toluene
(150 mL) and 10 mg para-toluenesulfonic acid (PTSA)
were added. The mixture was heated under reflux for 2 h. Af-
ter cooling, 80 mL saturated NaHCO3 solution was added.
The solution was extracted with 3ꢃ100 mL Et2O and the or-
ganic layer was dried and filtered. The solvent was removed
under reduced pressure. The residue was chromatographed
with PE/AcOEt to give product 2b.
1
are given in parts per million relative to Me4Si (0, H) or
CDCl3 (77.0, 13C). Mass spectra were recorded on Varian
MAT-44 or Finnigan MAT-TSQ 70 spectrometer. Melting
€
points were obtained on a Buchi Melting Point B-545 and
were uncorrected. Thin-layer chromatography (TLC) was
run on precoated silica gel plates (Merck 60F254). Flash
chromatography was carried out using flash silica gel 60
Merck (40–63 mm). Chiral GC analyses were performed
on CE instrument HRGC-5300 equipped with a flame
ionisation detector and Merck Hitachi integrators using
CHIRASIL-DEX CB column.
5.2.1. 2-(1-Naphthyl)-cyclohexenone 2b. RN:108842-56-
1
4; mp 107–108 ꢂC; 54%. H NMR (CDCl3, 200 MHz) d:
2.22 (pent, 2H, 6.6 Hz), 2.61 (td, 2H, J¼6.0, 4.5 Hz), 2.69
(t, 2H, J¼6.4 Hz), 7.05 (t, 1H, J¼4.5 Hz), 7.23 (dd, 1H,
J¼6.4, 1.6 Hz), 7.37–7.48 (m, 3H), 7.57–7.63 (m, 1H),
7.79–7.88 (m, 2H); 13C NMR (CDCl3, 50 MHz) d: 23.09,
26.43, 38.78, 125.20, 125.50, 125.60, 125.78, 126.99,
128.17, 128.28, 131.98, 133.46, 135.11, 140.49, 149.97,
198.03; IR (KBr): 780, 800, 1154, 1352, 1508, 1673,
2825, 2866, 2947, 3011, 3057 cmꢁ1; MS (EI, 70 eV) m/z
(%): 152 (24), 165 (100), 178 (18), 194 (38), 222.1 (92).
5.2. Synthesis of 2-aryl-cycloalkenones 2
General procedure: 23.03 mL (15.96 g, 57.59 mmol) n-BuLi
in 2.5 mol/L hexane was added at 0 ꢂC to a solution of

8456
Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
5.2.2. 2-(9-Anthracyl)-cyclohexenone 2c. Mp 156 ꢂC (de-
composition); 15%. H NMR (CDCl3, 200 MHz) d: 2.38
J¼15.1, 3.2, 3.6 Hz), 3.42 (d, 1H, 12.6 Hz), 6.99–7.05 (m,
2H), 7.22–7.41 (m, 8H); 13C NMR (CDCl3, 125 MHz) d:
5.08, ꢁ3.10, 27.36, 29.92, 34.47, 42.12, 58.08, 127.01,
127.52 (2C), 127.96 (2C), 128.81, 129.67 (2C), 133.82
(2C), 137.42, 137.99, 210.84; IR (film): 814, 837, 1110,
1
(pent, 2H, J¼6.8 Hz), 2.77 (td, 2H, J¼6.8, 4.2 Hz), 2.82 (t,
2H, J¼6.8 Hz), 7.08 (t, 1H, J¼4.2 Hz), 7.42 (m, 4H), 7.79
(m, 2H), 8.00 (m, 2H), 8.44 (s, 1H); 13C NMR (CDCl3,
50 MHz) d: 23.36, 26.74, 38.92, 124.99 (2C), 125.54 (2C),
125.71 (2C), 127.13, 128.66 (2C), 130.24 (2C), 131.37
(2C), 131.46, 138.56, 152.02, 198.12; IR (KBr): 735, 859,
1155, 1364, 1597, 1675, 2861, 2949, 3052 cmꢁ1; MS (CI)
m/z (%): 272.1 (24), 273.1 (100).
1249, 1427, 1596, 1710, 2850, 2925, 3028, 3066 cmꢁ1
;
MS (EI, 70 eV) m/z (%): 137.0 (100), 211.0 (54), 308.1
(3); HRMS (CI) calculated for C20H24OSi: 308.1596, found:
308.1598. HPLC (Chiral AD column, hexane 98%/i-PrOH
2%, 0.5 mL/min): 5.86, 7.47 min. (2R,3R)-3a: [a]2D0 ꢁ87.8
(c 0.41, EtOH), (2S,3S)-3a: [a]2D0 +85 (c 0.4, EtOH).
5.2.3. 2-(2-Phenoxy-phenyl)-cyclohexenone 2e. Mp 139–
1
140 ꢂC; 31%. H NMR (CDCl3, 200 MHz) d: 2.07 (pent,
5.3.2. trans-3-(Dimethylphenylsilyl)-2-(1-naphthyl)-
cyclohexanone 3b. (Method A) viscous oil; 34% (work-up
2H, J¼6.2 Hz), 2.41–2.54 (m, 4H), 6.81 (dd, 1H, J¼8.1,
1.7 Hz), 6.89 (t, 1H, J¼4.2 Hz), 6.99–7.36 (m, 7H), 7.86
(d, 1H, J¼8.3 Hz); 13C NMR (CDCl3, 50 MHz) d: 22.77,
26.15, 38.41, 117.83 (2C), 122.65 (2C), 128.43, 128.79
(2C), 130.98 (2C), 137.66, 148.44 (2C), 154.17 (2C),
197.18; IR (KBr): 754, 882, 1231, 1355, 1445, 1482,
1596, 1682, 2867, 2942, 3026, 3057 cmꢁ1; MS (CI) m/z
(%): 153.9 (100), 171.1 (13), 237.0 (5), 265.9 (3).
1
with saturated NH4Cl solution at 0 ꢂC). H NMR (CDCl3,
500 MHz) d: ꢁ026 (s, 3H, Me), ꢁ0.14 (s, 3H, Me), 1.77
(m, 1H), 1.94 (m, 1H, J¼12.8, 3.6 Hz), 2.01 (m, 1H), 2.14
(td, 1H, J¼12.5, 3.4 Hz), 2.24 (m, 1H), 2.5 (ddd, 1H,
J¼14, 12.8, 5.8 Hz), 2.62 (m, 1H), 4.14 (d, 1H,
J¼12.5 Hz), 7.18–7.45 (m, 9H), 7.68–7.75 (m, 2H), 7.79–
7.85 (m, 1H); 13C NMR (CDCl3, 125 MHz) d: ꢁ4.63,
ꢁ3.28, 27.82, 29.53, 33.64, 42.29, 55.3, 124.02, 125.03,
125.13, 125.55, 127.54 (2C), 127.95, 128.11, 128.83,
129.01, 131.97, 133.81 (2C), 134.09, 134.79, 137.39,
210.42; IR (film): 832, 1112, 1249, 1427, 1598 (C]C),
1709, 2856, 2931, 3046, 3067 cmꢁ1; MS (EI, 70 eV) m/z
(%): 135.1 (10), 177.7 (10), 205.9 (56), 252 (40), 280 (56),
358.1 (100); HRMS (EI, 70 eV) calculated for C24H26OSi:
358.1752, found: 358.1763. HPLC (Chiral AD column, hex-
ane 90%/i-PrOH 10%, 1 mL/min): 5.71, 6.81 min. (2R,3R)-
3b: [a]2D0 ꢁ231 (c 0.2, toluene), (2S,3S)-3b: [a]2D0 +209
(c 0.2, toluene).
5.2.4. 4,4-Dimethyl-2-(1-naphthyl)-cyclohexenone 2f. Mp
1
98–100 ꢂC; 46%. H NMR (CDCl3, 200 MHz) d: 1.32 (s,
6H, 2Me), 2.09 (t, 2H, J¼6.6 Hz), 2.73 (t, 2H, J¼6.6 Hz),
6.74 (s, 1H), 7.23 (dd, 1H, J¼7.0, 1.4 Hz), 7.41–7.49 (m,
3H), 7.57–7.62 (m, 1H), 7.80–7.87 (m, 2H); 13C NMR
(CDCl3, 50 MHz) d: 27.98 (2C), 33.47, 35.02, 36.33,
125.11, 125.34, 125.53, 125.77, 127.06, 128.12, 128.29,
132.09, 133.54, 134.84, 137.36, 159.03, 197.55; IR (KBr):
788, 805, 1146, 1353, 1466, 1508, 1592, 1677, 2863,
2956, 3001, 3056 cmꢁ1; MS (CI) m/z (%): 94.9 (28), 140.9
(100), 251.0 (6).
5.3.3. trans-2-(9-Anthracyl)-3-(dimethylphenylsilyl)-
cyclohexanone 3c. Mp 110–112 ꢂC; 20%. 1H NMR
(CDCl3, 500 MHz) d: ꢁ0.65 (s, 3H, Me), ꢁ0.32 (s, 3H,
Me), 1.90 (m, 1H), 2.12 (m, 1H), 2.18 (m, 1H, J¼13.2,
3.4 Hz), 2.36 (m, 3H), 2.61 (ddd, 1H, J¼12.7, 13.2,
3.0 Hz), 2.71 (ddd, 1H, J¼13.2, 6.3, 15.3 Hz), 2.88 (m,
1H), 4.90 (d, J¼12.7 Hz), 6.86 (dd, 2H, J¼7.9, 1.3 Hz),
7.06 (t, 2H, J¼7.4 Hz), 7.19 (m, 1H), 7.43 (m, 4H), 7.85
(m, 2H), 7.97 (m, 2H), 8.04 (m, 2H), 8.30 (s, 1H); 13C
NMR (CDCl3, 125 MHz) d: ꢁ5.11, ꢁ4.44, 27.75, 28.01,
32.71, 41.97, 52.48, 123.53, 124.17 (2C), 124.39, 125.52,
126.92, 127.08 (2C), 127.67, 128.29, 129.29 (2C), 129.60,
130.46, 131.50, 131.61, 131.80, 133.02 (2C), 136.98,
209.66; IR (KBr): 730, 816, 835, 1112, 1158, 1249, 1426,
5.3. Synthesis of trans-2-aryl-3-dialkylphenylsilyl cyclo-
alkanones 3a–h
General procedure (method B): 50 mL solution of PhMe2-
SiLi or PhEt2SiLi prepared from 6.4 mL (36.46 mmol)
chlorodimethylphenylsilane or PhEt2SiCl and 0.63 g
(91.15 mmol) lithium was added at ꢁ30 ꢂC to a suspension
of 1.63 g (18.23 mmol) CuCN (pre-dried) in 120 mLTHF in
a 500 mL three-neck flask under argon. The mixture was
stirred for 1 h at 0 ꢂC and cooled to ꢁ40 ꢂC.
To the above mixture, was added slowly 10 mL solution of
(1.57 g, 9.12 mmol) 2a in THF through a syringe. The reac-
tion mixture was stirred for 2.5 h at ꢁ23 ꢂC and then for 2 h
at 0 ꢂC. The reaction mixture was warmed to room temper-
ature in 1 h and 60 mL MeOH was added and the mixture
was stirred for 15 min. Then, 70 mL H2O was added. The
mixture was filtered through 5–6 cm Celite and washed
with CH2Cl2. The filtrate was extracted with 3ꢃ100 mL
CH2Cl2. The combined organic layers were washed with
brine, water, and dried over MgSO4, and concentrated under
the reduced pressure. The residue was chromatographed
with PE/Et2O to give 1.99 g trans-3a (71%).
1446, 1558, 1612, 1704, 2852, 2923, 3048, 3067 cmꢁ1
;
MS (CI) m/z (%): 58.9 (74), 98.9 (100), 136.8 (14), 209.0
(61), 231.0 (31), 393.3 (4), 408.3 (15), 409.4 (9); HRMS
(CI) calculated for C28H28OSi: 408.1909, found: 408.1904.
HPLC (Chiral AD column, hexane 98%/i-PrOH 2%, 1 mL/
min): 16.78, 28.58 min. (2R,3R)-3c: [a]2D0 ꢁ140 (c 0.5,
CHCl3), (2S,3S)-3c: [a]2D0 +142.6 (c 0.54, CHCl3).
5.3.4. trans-2-(2-Methoxyphenyl)-3-(dimethylphenyl-
silyl)-cyclohexanone 3d. Viscous oil; 67%. 1H NMR
(CDCl3, 500 MHz) d: ꢁ0.11 (s, 3H, Me), 0.08 (s, 3H, Me),
1.68 (qd, 1H, J¼12.7, 3.5 Hz), 1.85 (m, 1H), 1.90 (m, 1H),
1.98 (td, 1H, J¼12.9, 3.0 Hz), 2.18 (m, 1H), 2.44 (m, 1H,
J¼14.7, 12.7, 6.0 Hz), 2.57 (m, 1H), 3.76 (s, 3H, MeO),
3.82 (d, 1H, J¼12.9 Hz), 6.82 (d, 1H, J¼8.2 Hz), 6.90 (t,
1H, J¼7.4 Hz), 7.00 (dd, 1H, J¼7.4, 1.5 Hz), 7.22 (td, 1H,
5.3.1. trans-3-(Dimethylphenylsilyl)-2-phenyl-cyclohexa-
none 3a. Viscous oil; 71%. H NMR (CDCl3, 500 MHz)
1
d: ꢁ0.132 (s, 3H, Me), ꢁ0.003 (s, 3H, Me), 1.70 (m, 1H),
1.77 (td, 1H, J¼12.6, 3.2 Hz), 1.86 (m, 1H), 1.91 (m, 1H),
2.21 (m, 1H), 2.43 (td, J¼13.1, 15.1, 5.6 Hz), 2.54 (dt, 1H,

Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
8457
J¼8.2, 7.4, 1.3 Hz), 7.30–7.40 (m, 5H); 13C NMR (CDCl3,
125 MHz) d: ꢁ5.08, ꢁ0.11, 27.40, 29.05, 32.07, 41.93,
52.70, 54.91, 110.45, 120.07, 126.97, 127.31 (2C), 128.04,
128.50, 130.99, 133.65 (2C), 137.91, 156.93, 210.21; IR
(film): 774, 827, 830, 1118, 1247, 1427, 1494, 1588, 1602,
1708, 2903, 2955, 3048, 3068 cmꢁ1; MS (CI) m/z (%):
58.9 (100), 135.1 (16), 261.0 (13), 323.1 (16), 338.1 (9),
339.2 (7); HRMS (CI) calculated for C21H26O2Si:
338.1702, found: 338.1697. HPLC (Chiral AD column,
hexane 99%/i-PrOH 1%, 1 mL/min): 10.83, 14.46 min.
(2R,3R)-3d: [a]2D0 ꢁ84 (c 0.88, EtOH), (2S,3S)-3d: [a]2D0
+74 (c 0.59, EtOH).
1H, J¼12.7 Hz), 7.23 (d, 1H, J¼7.0 Hz), 7.29 (dd, 2H,
J¼6.6, 5.5 Hz), 7.35 (d, 3H, J¼7.0 Hz), 7.40 (t, 1H,
J¼6.6 Hz), 7.48 (m, 2H), 7.76 (d, 1H, J¼8.0 Hz), 7.77 (m,
1H), 7.87 (m, 1H); 13C NMR (CDCl3, 125 MHz) d: ꢁ5.03,
ꢁ4.39, 23.32, 31.65, 38.59, 54.84, 123.74, 125.04, 125.36,
125.76, 126.24, 127.58 (2C), 127.65, 128.89, 129.12,
131.89, 133.89 (2C), 134.05, 135.14, 136.14, 218.93; IR
(film): 776, 838, 1250, 1427, 1596, 1737, 2852, 2924,
2956, 3046, 3050 cmꢁ1; MS (CI) m/z (%): 58.7 (100),
127.0 (16), 135.0 (14), 209.0 (75), 315.9 (3), 345.0 (3);
HRMS (CI) calculated for C23H24OSi: 344.1596, found:
344.1596. HPLC (Chiral OD-H column, hexane 99%/
i-PrOH 1%, 1 mL/min): 24.06, 31.77 min. (2R,3R)-3g:
[a]2D0 ꢁ9.1 (c 0.55, EtOH), (2S,3S)-3g: [a]2D0 +13.6 (c 0.44,
EtOH).
5.3.5. trans-2-(2-Phenoxyphenyl)-3-(dimethylphenyl-
silyl)-cyclohexanone 3e. Viscous oil; 57%. 1H NMR
(CDCl3, 500 MHz) d: ꢁ0.05 (s, 3H, Me), 0.21 (s, 3H, Me),
1.75 (m, 1H, J¼13.3, 13.0 Hz), 1.85 (m, 1H), 1.91 (m,
1H), 2.10 (td, 1H, J¼13.0, 2.9 Hz), 2.16 (m, 1H), 2.38 (td,
1H, J¼13.1, 13.6, 5.5 Hz), 2.49 (ddd, J¼13.6, 4.1,
3.1 Hz), 3.90 (d, 1H, J¼13.0 Hz), 6.70 (d, 1H, J¼7.8 Hz),
6.95 (m, 1H), 7.04 (m, 1H), 7.08 (m, 2H), 7.13 (m, 2H),
7.15 (m, 2H), 7.32 (m, 3H), 7.39 (m, 2H); 13C NMR
(CDCl3, 125 MHz) d: ꢁ4.74, ꢁ2.80, 27.70, 29.22, 31.71,
41.92, 53.60, 117.3 (2C), 118.47, 121.60, 122.71, 127.55
(2C), 128.18, 128.30 (2C), 128.69, 129.38, 131.60, 133.70
(2C), 138.25, 155.32, 156.10, 209.22; IR (film): 770, 813,
833, 1112, 1246, 1427, 1453, 1488, 1599, 1710, 2854,
2925, 3046, 3075 cmꢁ1; MS (CI) m/z (%): 59.0 (100),
135.1 (8), 153.7 (28), 225 (19), 385.2 (5), 401.3 (5);
HRMS (CI) calculated for C26H28O2Si: 400.1859, found:
400.1918. HPLC (Chiral OD-H column, hexane 98%/
i-PrOH 2%, 1 mL/min): 10.76, 13.66 min. (2R,3R)-3e:
[a]2D0 ꢁ43 (c 2.0, EtOH), (2S,3S)-3e: [a]2D0 +45 (c 1.9,
EtOH).
5.3.8. trans-3-(Diethylphenylsilyl)-2-phenyl-cyclohexa-
none 3h. Mp 44–46 ꢂC; 70%. 1H NMR (CDCl3, 200 MHz)
d: 0.095 (m, 1H), 0.28 (m, 1H), 0.64 (m, 2H), 0.60–0.87
(m, 6H), 1.71–2.04 (m, 4H), 2.18–2.52 (m, 3H), 3.31 (d,
1H, J¼11.4 Hz), 6.93–6.98 (dd, 2H, J¼7.6, 5.7 Hz), 7.25–
7.36 (m, 8H); 13C NMR (CDCl3, 125 MHz) d: 1.38, 2.35,
7.10, 7.26, 27.46, 30.00, 32.05, 42.17, 58.74, 127.11,
127.59 (2C), 127.88 (2C), 128.97, 129.76 (2C), 134.71
(2C), 134.94, 138.18, 211.07; IR (KBr): 716, 763, 1006,
1108, 1160, 1236, 1427, 1455, 1601, 1711, 2873, 2954,
3027, 3066 cmꢁ1; MS (CI) m/z (%): 102.9 (8), 156.9
(100), 162.9 (19), 259.1 (30), 307.2 (31), 336.1 (55), 337.2
(15); HRMS (CI) calculated for C22H28OSi: 336.1909,
found: 336.1910. HPLC (Chiral AD column, hexane 99%/
i-PrOH 1%, 1 mL/min): 12.14, 14.97 min. (2R,3R)-3h:
[a]2D0 ꢁ73 (c 1.0, EtOH), (2S,3S)-3h: [a]2D0 +69 (c 1.0,
EtOH).
5.3.9. cis-3-(Dimethylphenylsilyl)-2-phenyl-cyclohexa-
none 4a. (Method A: work-up with saturated NH4Cl solution
at 0 ꢂC), mp 79–80 ꢂC (racemic, but each enantiomer is vis-
cous oil); 70%. 1H NMR (CDCl3, 500 MHz) d: 0.036 (s, 3H),
0.059 (s, 3H), 1.75 (ddd, 1H, J¼5.7, 13.6, 3.4 Hz), 1.81 (dq,
1H, J¼13.0, 3.4, 3.7, 3.7 Hz), 1.85 (m, 1H), 2.16 (qd, 1H,
J¼13.0, 13.0, 13.6, 3.4 Hz), 2.31 (m, 1H), 2.37 (dt, 1H,
J¼15.0, 3.4, 3.7 Hz), 2.77 (td, 1H, J¼15.0, 13.6, 6.1 Hz),
3.66 (d, 1H, J¼5.7 Hz), 7.18–7.38 (m, 10H); 13C NMR
(CDCl3, 125 MHz) d: ꢁ4.15, ꢁ3.98, 22.28, 29.27, 32.50,
38.62, 58.17, 127.11, 127.58 (2C), 128.32 (2C), 128.89,
129.71 (2C), 133.66 (2C), 137.59, 138.26, 211.46; IR
(KBr): 811, 833, 1112, 1248, 1427, 1598, 1706, 2862,
2951, 3024, 3067 cmꢁ1; MS (+CI) m/z (%): 74.9 (27),
134.9 (11), 148.9 (100), 211.0 (45), 293.0 (3), 308.1 (6,
M+), 309.5 (2, M++1); Elemental analysis calculated for
C20H24OSi: C 77.86%, H 7.84%; found: C 77.12%, H
7.69%. HPLC (chiral AD column, hexane 99.5%/i-PrOH
0.5%, 1 mL/min): 18.36, 26.57 min. [a]2D0 +16.3 (c 1.1,
EtOH), [a]2D0 ꢁ15.9 (c 1.35, EtOH).
5.3.6. trans-3-(Dimethylphenylsilyl)-4,4-dimethyl-2-(1-
naphthyl)-cyclohexanone 3f. Mp 93–95 ꢂC, 50%. 1H
NMR (CDCl3, 500 MHz) d: ꢁ0.11 (s, 3H, MeSi), 0.30 (s,
3H, MeSi), 1.12 (s, 3H, Me), 1.41 (s, 3H, Me), 1.86 (ddd,
J¼13.6, 3.8, 6.4 Hz), 2.19 (td, J¼13.6, 11.7, 6.2 Hz), 2.45
(d, J¼11.1 Hz), 2.62 (ddd, 1H, J¼16.0, 3.8, 6.2 Hz), 2.69
(ddd, 1H, J¼16.0, 6.4, 11.7 Hz), 4.50 (d, 1H, J¼11.1 Hz),
7.12 (m, 2H), 7.16 (m, 2H), 7.18 (m, 1H), 7.29 (dd, 1H,
J¼8.0, 7.5 Hz), 7.36 (d, 1H, J¼7.0 Hz), 7.46 (td, 1H,
J¼7.5, 1.0 Hz), 7.51 (td, 1H, J¼6.9, 1.3 Hz), 7.69 (d,
1H, J¼8.1 Hz), 7.81 (d, 1H, J¼7.8 Hz), 7.96 (s, 1H); 13C
NMR (CDCl3, 125 MHz) d: ꢁ1.17, 0.00, 24.02, 32.02,
34.02, 36.60, 41.94, 43.24, 51.40, 123.99, 124.59, 124.92,
125.52, 127.13, (2C), 127.28, 127.83, 128.00, 128.75,
132.05, 133.10 (2C), 133.83, 134.83, 139.43, 211.27; IR
(KBr): 775, 815, 831, 1110, 1250, 1426, 1511, 1597, 1708,
2864, 2952, 3044, 3066 cmꢁ1; MS (CI) m/z (%): 136.9
(69), 152.8 (26), 235.0 (100), 309.2 (40), 371.3 (16), 387.4
(10); HRMS (CI) calculated for C26H30OSi: 386.2066,
found: 386.2070. HPLC (Chiral OD-H column, hexane
96%/i-PrOH 4%, 1 mL/min): 14.36, 17.82 min. (2R,3S)-3f:
[a]2D0 ꢁ63 (c 0.87, CHCl3), (2S,3R)-3f: [a]2D0 +61 (c 0.85,
CHCl3).
5.3.10. cis-3-(Dimethylphenylsilyl)-2-(1-naphthyl)-cyclo-
hexanone 4b. (Method A), viscous oil, 23%. 1H NMR
(CDCl3, 200 MHz) d: 0.034 (s, 3H), 0.17 (s, 3H), 1.89–
2.17 (m, 3H), 2.23–2.44 (m, 3H), 2.78 (td, 1H, J¼13.2,
13.2, 5.0 Hz), 4.57 (d, 1H, J¼5.6 Hz), 7.17–7.51 (m, 8H),
7.72–7.84 (m, 3H), 8.16–8.21 (m, 1H); 13C NMR (CDCl3,
50 MHz): ꢁ3.62, ꢁ3.18, 24.09, 30.53, 33.78, 38.06, 52.03,
124.21, 124.62, 125.59, 126.49, 126.99, 127.55 (2C),
5.3.7. trans-3-(Dimethylphenylsilyl)-2-(10-naphthyl)-
cyclopentanone 3g. Viscous oil; 73%. H NMR (CDCl3,
1
500 MHz) d: 0.06 (s, 3H, Me), 0.09 (s, 3H, Me), 1.89 (m,
1H), 2.18 (m, 1H), 2.25 (m, 1H), 2.51 (m, 2H), 3.79 (d,

8458
Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
127.99, 128.62, 128.90, 132.50, 133.68 (2C), 133.88,
134.53, 137.75, 212.07; IR (film): 791, 832, 1118, 1254,
13.6 Hz), 7.12 (dd, 1H, J¼8.4, 1.3 Hz), 7.32 (t, 2H,
J¼7.4 Hz), 7.36 (d, 1H, J¼1.3 Hz), 7.39 (m, 1H), 7.41 (m,
1H), 7.43 (m, 1H), 7.45 (dd, 2H, J¼7.9, 1.5 Hz), 7.66 (d,
1H, J¼8.4 Hz), 7.69 (d, 1H, J¼7.6 Hz), 7.76 (d, 1H,
J¼7.5 Hz); 13C NMR (CDCl3, 125 MHz) d: ꢁ3.18, ꢁ2.74,
25.42, 29.00, 31.11, 36.23, 41.23, 53.68, 125.05, 125.60,
127.20, 127.39 (2C), 127.52, 127.55, 127.86 (2C), 129.07,
131.85, 133.24, 133.69 (2C), 137.59, 137.68, 213.64; IR
(KBr): 735, 782, 817, 1039, 1114, 1251, 1427, 1505, 1601,
1634, 1693, 2854, 2910, 2949, 3023, 3063 cmꢁ1; MS
(+CI) m/z (%): 135.0 (27), 141.0 (100), 295.0 (24), 373.4
(22, M++1); HRMS (CI) calculated for C25H28OSi:
372.1909, found: 372.1894. HPLC (OD-H column, hexane
99%/i-PrOH 1%, 1 mL/min): 11.24, 13.37 min. (2R,3R)-
5b: [a]2D0 ꢁ89 (c 1.0, EtOH), (2S,3S)-5b: [a]2D0 +67 (c
0.53, EtOH).
1427, 1593, 1708, 2854, 2925, 2954, 3048, 3068 cmꢁ1
;
MS (+CI) m/z (%): 135.0 (17), 207.1 (100), 273 (40),
358.2 (30, M+), 359.1 (10, M++1); HRMS (CI) calculated
for C24H26OSi: 358.1752, found: 358.1760. HPLC (chiral
AS column, hexane 95%/i-PrOH 5%, 1 mL/min): 6.77,
14.16 min; [a]2D0 ꢁ7.8 (c 1.0, EtOH, Peak1), +8.2 (c 1.0,
EtOH, Peak2).
5.4. Synthesis of trans-2-arylmethyl-3-dialkylphenylsilyl
cycloalkanones 5a–c
General procedure: under argon, to a suspension of 17.56 g
(92.21 mmol, 1.5 equiv) CuI in 120 mL dry THF and 40 mL
hexamethylphosphoramide (HMPA) in a 500 mL three-neck
flask, was added at ꢁ30 ꢂC, 120 mL solution of dimethyl-
phenylsilyllithium prepared from 31 mL (31.48 g,
184.41 mmol, 3 equiv) chlorodimethylphenylsilane and
3.84 g (553.23 mmol, 9 equiv) lithium. The mixture was
stirred for 1 h at 0 ꢂC and cooled down to ꢁ78 ꢂC. Then
5.95 mL (5.91 g, 61.47 mmol, 1 equiv) 2-cyclohexene-1-
one was slowly added through a syringe. The reaction mix-
ture was warmed to ꢁ23 ꢂC and continued to stir for 3 h
and cooled down to ꢁ78 ꢂC. Then, 21 mL (29.62 g,
127.73 mmol, 2.82 equiv) benzyl bromide was added drop-
wise. After being stirred for 5 h at ꢁ23 ꢂC and 15 min at
0 ꢂC, the reaction was stopped with 100 mL saturated
NH4Cl solution. The mixture was filtered through a pad of
Celite and washed with CH2Cl2. The filtrate was extracted
with 3ꢃ150 mL CH2Cl2, washed with brine and water.
The collected extracts were dried, filtered and evaporated,
the crude product was flash chromatographed to give
17.0 g 5a (85% yield, Rf¼0.31, EP/Et2O¼8/1) as a white
solid.
5.4.3. trans-3-(Dimethylphenylsilyl)-2-(1-naphthyl-
methyl)-cyclohexanone 5c. Viscous oil; 39%. 1H NMR
(CDCl3, 500 MHz) d: 0.22 (s, 3H), 0.26 (s, 3H), 1.53 (q,
1H, J¼6.2 Hz), 1.79 (m, 1H), 1.97 (m, 2H), 2.14 (m, 1H),
2.35 (dt, 1H, J¼14.1, 6.0, 6.0 Hz), 2.54 (m, 1H), 3.00 (q,
1H, J¼7.8, 7.4 Hz), 3.18 (dd, 1H, J¼7.4, 14.0 Hz), 3.40
(dd, 1H, J¼7.8, 14.0 Hz), 7.17 (d, 1H, J¼7.0 Hz), 7.21 (m,
2H), 7.29 (m, 3H), 7.34 (dd, 1H, J¼7.0, 8.2 Hz), 7.40 (m,
1H), 7.44 (m, 1H), 7.70 (d, 1H, J¼8.2 Hz), 7.79 (d, 1H,
J¼8.3 Hz), 7.82 (dd, 1H, J¼8.6, 1.4 Hz); 13C NMR
(CDCl3, 125 MHz) d: ꢁ3.58, ꢁ3.15, 23.72, 27.48, 29.78,
34.66, 40.12, 51.56, 123.57, 124.95, 125.27, 125.76,
126.57, 126.94, 127.68 (2C), 128.57, 128.87, 131.80,
133.46 (2C), 133.86, 135.08, 137.53, 213.53; IR (film):
732, 777, 810, 832, 1110, 1250, 1426, 1596, 1653, 1706,
2856, 2949, 3030, 3064 cmꢁ1; MS (+CI) m/z (%): 95 (22),
134.9 (44), 140.9 (60), 221.0 (100), 357.1 (12), 372.6 (42),
373.1 (44, M++1); HRMS (CI) calculated for C25H28OSi:
372.1909, found: 372.1892. HPLC (OD-H column, Hexane
99%/i-PrOH 1%, 1 mL/min): 16.15, 18.02 min. (2R,3R)-5c:
[a]2D0 ꢁ95.7 (c 0.6, EtOH), (2S,3S)-5c: [a]2D0 +97 (c 0.62,
EtOH).
5.4.1. trans-2-Benzyl-3-(dimethylphenylsilyl)-cyclohexa-
1
none 5a. Mp 55–58 ꢂC; 85%. H NMR (CDCl3, 500 MHz,
42 ꢂC) d: 0.349 (s, 3H), 0.357 (s, 3H), 1.42 (td, 1H, J¼8.6,
8.6, 3.8 Hz), 1.70 (m, 1H), 1.84 (m, 1H), 1.99 (m, 2H),
2.28 (m, 1H), 2.41 (m, 1H), 2.72 (m, 2H), 2.90 (dd, 1H,
J¼4.4, 14.8 Hz), 7.0 (dd, 2H, J¼7.4, 1.4 Hz), 7.14 (m,
1H), 7.20 (m, 2H), 7.35 (m, 3H), 7.45 (dd, 2H, J¼7.9,
1.5 Hz); 13C NMR (CDCl3, 125 MHz, 42 ꢂC) d: ꢁ3.28,
ꢁ2.93, 25.21, 28.70, 30.95, 36.42, 41.04, 53.56, 125.81,
128.03 (2C), 127.85 (2C), 128.91 (2C), 129.03, 133.66
(2C), 137.81, 140.02, 213.38; IR (KBr): 734, 773, 812,
832, 933, 1111, 1250, 1427, 1453, 1495, 1603, 1709,
2858, 2950, 3025, 3066 cmꢁ1; MS (CI) m/z (%): 135.0
(11), 171.0 (100), 245.1 (56), 307.1 (24), 322.1 (2), 323.2
(16); HRMS (CI) calculated for C21H26OSi: 322.1752,
found: 322.1744. HPLC (Chiral OD-H column, hexane
99%/i-PrOH 1%, 1 mL/min): 12.69, 15.41 min. (2R,3R)-
5a: [a]2D0 ꢁ79 (c 1.0, EtOH), (2S,3S)-5a: [a]2D0 +86 (c 1.0,
EtOH).
5.5. Synthesis of ENP trans-1-dialkylphenylsilyl-2-aryl-
cycloalkanes 7a–h and trans-1-dialkylphenylsilyl-2-
arylmethyl-cyclohexanones 8a–c
General procedure: to a 50 mL one-neck flask with a stirring
bar and a condenser, were added 0.787 g (2.194 mmol,
1 equiv) (+) (2S,3S)-3b, 0.505 g (97%, 2.632 mmol,
1.2 equiv) para-toluenesulfonhydrazide in 15 mL EtOH.
The solution was heated at 60 ꢂC for 2 h (controlled by
TLC) and cooled to room temperature. The solvent was re-
moved under the reduced pressure to afford the correspond-
ing tosylhydrazone, which was used for the next step without
isolation.
To the solution of the obtained tosylhydrazone in 20 mL
EtOH/MeOH (1:1), 0.726 g (10.97 mmol, 5 equiv)
NaBH3(CN), 0.747 g (5.485 mmol, 2.5 equiv) ZnCl2 were
added. The mixture was heated at 60 ꢂC for 3 h and cooled
to room temperature. The mixture was filtered through 5–
6 cm Celite and washed with CH2Cl2. After concentration,
the residue was diluted with 5 mL CH2Cl2 and 5 mL satu-
rated NaHCO3 solution. The mixture was filtered through
5–6 cm Celite and washed with CH2Cl2. The filtrate was
5.4.2. trans-3-(Dimethylphenylsilyl)-2-(2-naphthyl-
1
methyl)-cyclohexanone 5b. Mp 92–93 ꢂC; 41%. H NMR
(CDCl3, 500 MHz) d: 0.36 (s, 3H), 0.37 (s, 3H), 1.44 (td,
1H, J¼8.6, 8.6, 3.8 Hz), 1.73 (m, 1H), 1.86 (m, 1H), 2.02
(m, 2H), 2.29 (ddd, 1H, J¼14.4, 9.7, 5.3 Hz), 2.41 (td, 1H,
J¼6.2, 6.2, 14.4 Hz), 2.80 (td, 1H, J¼8.6, 8.4, 5.4 Hz),
2.84 (dd, 1H, J¼5.4, 13.6 Hz), 3.03 (dd, 1H, J¼8.4,

Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
8459
extracted with 3ꢃ10 mL CH2Cl2 and the collected organic
layers were dried over MgSO4, filtered and evaporated.
Flash chromatograph of the residue afforded 0.34 g (+)
(1S,2R)-9b (45%, viscous oil, Rf¼0.57/hexane).
[a]2D0 +25 (c 1.0, EtOH); (1R,2S)-7e: 25%, viscous oil,
[a]2D0 ꢁ21 (c 1.0, EtOH).
1H NMR (CDCl3, 200 MHz) d: ꢁ0.13 (s, 3H), 0.18 (s, 3H),
0.99–1.70 (m, 6H), 1.72–2.0 (m, 3H), 3.0–3.2 (br m, 1H),
6.76 (d, 1H, J¼7.9 Hz), 6.92–7.12 (m, 3H), 7.22–7.44 (m,
10H); 13C NMR (CDCl3, 50 MHz) d: ꢁ4.77, ꢁ2.52,
27.10, 27.46, 28.62, 29.05, 33.68, 40.05, 118.5 (2C),
122.82, 126.81 (2C), 127.47 (2C), 127.69, 127.59, 128.38
(2C), 133.6, 133.83 (2C), 133.98, 140.1, 154.30, 156.09;
IR (film): 769, 812, 834, 1064, 1112, 1227, 1246, 1426,
1443, 1482, 1596, 2847, 2922, 3020, 3066 cmꢁ1; MS
(+CI) m/z (%): 135.1 (11), 169.2 (13), 271.1 (100), 309.5
(4), 371.3 (9), 387.7 (3, M++1); HRMS (CI) calculated for
C26H30OSi: 386.2066, found: 386.2096.
5.5.1. trans-1-(Dimethylphenylsilyl)-2-phenyl-cyclohex-
ane 7a. (1R,2S)-7a: 44%, viscous oil, [a]2D0 +33.3 (c 0.21,
EtOH); (1S,2R)-7a: 31%, viscous oil, [a]2D0 ꢁ38.6 (c 0.44,
EtOH).
1H NMR (CDCl3, 500 MHz) d: ꢁ0.18 (s, 3H), 0.004 (s, 3H),
1.28 (m, 3H), 1.38 (m, 1H), 1.48 (m, 1H), 1.83 (m, 4H), 2.46
(td, 1H, J¼8.2, 8.2, 11.0 Hz), 7.10–7.28 (m, 5H), 7.30–7.45
(m, 5H); 13C NMR (CDCl3, 125 MHz) d: ꢁ4.88, ꢁ2.96,
26.96, 27.43, 28.31, 31.11, 37.94, 46.69, 125.98, 127.27
(2C), 127.77 (2C), 128.06 (2C), 128.28, 133.84 (2C),
139.02, 147.47; IR (film): 775, 813, 834, 1111, 1248,
5.5.5. trans-1-(Dimethylphenylsilyl)-6,6-dimethyl-2-(1-
naphthyl)-cyclohexane 7f. (1R,2R)-7f: 31%, viscous oil,
[a]2D0 +69.9 (c 0.83, EtOH); (1S,2S)-7f, 27%, viscous oil,
[a]2D0 ꢁ68.1 (c 0.83, EtOH).
1427, 1445, 1491, 1600, 2849, 2922, 3025, 3066 cmꢁ1
;
MS (+CI) m/z (%): 134.8 (27), 136.1 (5), 216.9 (100),
279.0 (24), 294.2 (2), 295.6 (1); HRMS (CI) calculated for
C20H26Si: 294.1803, found: 294.1794.
1H NMR (CDCl3, 200 MHz) d: 0.44 (s, 3H), 0.54 (s, 3H),
1.05 (s, 3H), 1.33 (s, 3H), 1.20–1.45 (m, 2H), 1.63–1.98
(m, 4H), 2.14–2.29 (m, 1H), 3.30–3.48 (m, 1H), 7.27–7.68
(m, 10H), 7.79–7.84 (dd, 1H, J¼6.6, 1.6 Hz), 7.95 (d, 1H,
J¼6.2 Hz); 13C NMR (CDCl3, 50 MHz) d: 0.3, 0.86,
29.22, 30.32, 30.86, 32.44, 33.58, 35.81, 36.20, 38.26,
122.40, 123.19, 125.18, 125.57 (2C), 126.26, 127.74 (2C),
128.53, 128.95, 131.45, 133.79 (2C), 133.80, 141.10,
143.51; IR (film): 776, 813, 831, 1112, 1249, 1427, 1509,
1597, 2864, 2948, 3047, 3067 cmꢁ1; MS (+CI) m/z (%):
76.8 (17), 135.0 (16), 136.8 (19), 194.8 (100), 271.1 (47),
357.1 (4), 372.7 (2, M+), 373.2 (3, M++1); HRMS (CI) cal-
culated for C26H32Si: 372.2273, found: 372.2265.
5.5.2. trans-1-(Dimethylphenylsilyl)-2-(1-naphthyl)-cy-
clohexanone 7b. (1S,2R)-7b: 45%, viscous oil, [a]2D0 +35.7
(c 0.7, EtOH); (1R,2S)-7b: 39%, viscous oil, [a]2D0 ꢁ32.8
(c 0.7, EtOH).
1H NMR (CDCl3, 200 MHz) d: ꢁ0.33 (s, 3H), 0.13 (s, 3H),
1.15–1.52 (m, 5H), 1.70–1.95 (m, 4H), 3.20–3.40 (br m,
1H), 7.02–7.16 (m, 3H), 7.17–7.20 (m, 2H), 7.22–7.32 (m,
2H), 7.40–7.50 (m, 2H), 7.64 (d, 1H, J¼7.4 Hz), 7.80–
7.88 (dd, 1H, J¼5.8, 3.8 Hz), 8.00–8.01 (m, 1H); 13C
NMR (CDCl3, 50 MHz) d: ꢁ4.23, ꢁ2.89, 27.45, 27.75,
29.00, 30.82, 38.55, 39.39, 122.91, 124.84, 125.07, 125.37,
125.44, 126.24, 127.29 (2C), 128.29, 128.89, 130.93,
133.78 (2C), 134.00, 139.05, 143.60; IR (film): 776, 817,
834, 1112, 1248, 1427, 1444, 1511, 1596, 2848, 2924,
3046, 3067 cmꢁ1; MS (EI, 70 eV) m/z (%): 83.8 (100),
135.1 (21), 208.1 (23), 267.2 (86), 271.1 (51), 329.1 (2),
344.2 (12).
5.5.6. trans-1-(Dimethylphenylsilyl)-2-(1-naphthyl)-
cyclopentane 7g. (1S,2R)-7g: 32%, viscous oil, [a]2D0 +15
(c 0.2, EtOH); (1R,2S)-7g: 32%, viscous oil, [a]2D0 ꢁ26
(c 0.39, EtOH).
1H NMR (CDCl3, 500 MHz) d: 0.03 (s, 3H), 0.07 (s, 3H),
1.60 (m, 1H), 1.69 (m, 2H), 1.80 (m, 2H), 2.07 (m, 1H),
2.20 (m, 1H), 3.67 (td, 1H, J¼8.6, 8.6, 10.2 Hz), 7.25 (m,
2H), 7.30 (m, 1H), 7.36 (m, 2H), 7.37 (m, 1H), 7.43 (m,
1H), 7.46 (m, 2H), 7.66 (dd, 1H, J¼7.4, 1.6 Hz), 7.84
(m, 1H), 8.08 (m, 1H); 13C NMR (CDCl3, 125 MHz) d:
ꢁ4.54, ꢁ3.56, 26.07, 28.95, 32.54, 37.86, 42.94, 123.37,
123.38, 125.01, 125.30 (2C), 126.03, 127.36 (2C), 128.56,
128.70, 131.85, 133.82 (3C), 138.38, 142.36; IR (film):
793, 830, 1060, 1118, 1245, 1427, 1591, 2865, 2955,
3049, 3068 cmꢁ1; MS (EI, 70 eV) m/z (%): 56.8 (75),
135.0 (14), 151.0 (37), 193.0 (58), 271.0 (100), 330.1 (5,
M+); HRMS (EI) calculated for C23H26Si: 330.1804, found:
330.1797.
5.5.3. trans-1-(Dimethylphenylsilyl)-2-(2-methoxy-
phenyl)-cyclohexane 7d. (1R,2S)-7d: 57%, viscous oil,
[a]2D0 +20 (c 0.50, EtOH); (1S,2R)-7d: 51%, viscous oil,
[a]2D0 ꢁ13.3 (c 1.2, EtOH).
1H NMR (CDCl3, 500 MHz) d: ꢁ0.195 (s, 3H), 0.032 (s,
3H), 1.25 (m, 2H), 1.38 (m, 2H), 1.49 (m, 1H), 1.76 (m,
4H), 3.01 (td, 1H, J¼11.0, 11.0, 3.1 Hz), 3.77 (s, 3H), 6.76
(d, 1H, J¼8.2 Hz), 6.82 (td, 1H, J¼7.4, 7.4, 1.1 Hz), 7.09
(td, 1H, J¼7.4, 7.4, 1.7 Hz), 7.12 (dd, 1H, J¼7.4, 1.7 Hz),
7.25 (m, 3H), 7.32 (m, 2H); 13C NMR (CDCl3, 125 MHz)
d: ꢁ4.78, ꢁ3.25, 27.20, 27.66, 28.66, 30.00, 36.43, 38.68,
54.97, 110.49, 120.40, 126.60, 127.16 (2C), 128.06,
128.78, 133.74, 133.75 (2C), 139.67, 156.57; IR (film):
769, 815, 834, 1111, 1243, 1427, 1439, 1463, 1491, 1585,
1599, 2847, 2925, 3033, 3067 cmꢁ1; MS (+CI) m/z (%):
120.68 (64), 134.8 (22), 136.8 (14), 188.9 (79), 247.0
(100), 309.1 (41), 324.1 (13), 325.1 (7); HRMS (CI) calcu-
lated for C21H28OSi: 324.1909, found: 324.1905.
5.5.7. trans-1-(Diethylphenylsilyl)-2-phenyl-cyclohexane
7h. (1R,2S)-7h: 35%, viscous oil, [a]2D0 +56 (c 0.8, EtOH);
(1S,2R)-7h: 31%, viscous oil, [a]2D0 ꢁ59 (c 0.8, EtOH).
1H NMR (CDCl3, 200 MHz) d: 0.12 (m, 1H), 0.27 (m, 1H),
0.53 (q, 2H, J¼7.6 Hz), 0.77 (t, 6H, J¼7.7 Hz), 1.10–1.48
(m, 5H), 1.65–1.90 (m, 4H), 2.21–2.40 (m, 1H), 7.03–7.07
(dd, 2H, J¼7.9, 2.1 Hz), 7.14–7.31 (m, 8H); 13C NMR
5.5.4. trans-1-(Dimethylphenylsilyl)-2-(2-phenoxy-
phenyl)-cyclohexane 7e. (1S,2R)-7e: 20%, viscous oil,

8460
Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
(CDCl3, 50 MHz) d: 1.76, 2.34, 7.28, 7.52, 26.97, 27.62,
28.48, 28.92, 38.28, 46.54, 126.06, 127.33 (2C), 127.87
(2C), 128.01 (2C), 128.41, 134.69 (2C), 136.68, 147.62;
IR (film): 734, 757, 1007, 1057, 1107, 1235, 1427, 1444,
1490, 1600, 2873, 2919, 3025, 3067 cmꢁ1; MS (+CI) m/z
(%): 163.0 (24), 164.3 (4), 245.1 (97), 293.2 (100), 323.3
(1, M++1); HRMS (CI) calculated for C22H30Si: 322.2116,
found: 322.2120.
133.60, 133.85 (2C), 137.37, 139.57; IR (film): 767, 784,
809, 832, 1112, 1247, 1426, 1444, 1508, 1595, 2849,
2927, 3045, 3066 cmꢁ1; MS (+CI) m/z (%): 99.0 (100),
135.0 (10), 141.1 (11), 217.0 (5), 281.1 (12), 343.2 (4),
358.4 (1, M+); HRMS (CI) calculated for C25H30Si:
358.2117, found: 358.2120.
5.6. Synthesis of ENP silyl dithioketals 10a,b
5.5.8. trans-2-Benzyl-1-(dimethylphenylsilyl)-cyclohex-
ane 8a. (1S,2R)-8a: 54%, viscous oil, [a]2D0 +11 (c 0.48,
General procedure: to a 25 mL two-neck flask equipped
with a tube of blue silica gel and stirring bar, were added
0.3 g (0.972 mmol, 1 equiv) (ꢁ)-4a, 0.101 mL (114 mg,
1.22 mmol, 1.25 equiv) 1,2-ethanedithiol and 8 mL dry
CH2Cl2. The solution was cooled to ꢁ40 ꢂC and 0.032 mL
(55 mg, 0.29 mmol, 0.3 equiv) TiCl4 was added under argon.
The reaction mixture was warmed to room temperature and
stirred for additional 5 h before the reaction was quenched
with 3 mL saturated NaHCO3 solution. The mixture was ex-
tracted three times with CH2Cl2. The organic phases were
dried, filtered and evaporated in vacuum. Purification of
the residue by flash chromatography (EP/Et2O¼30/1,
Rf¼0.33) gave 0.62 g (90%, yield) product (ꢁ)-10a as vis-
cous oil.
20
EtOH); (1R,2S)-8a: 85%, viscous oil, [a]D ꢁ14.3 (c
0.42, EtOH).
1H NMR (CDCl3, 500 MHz) d: 0.38 (s, 3H), 0.42 (s, 3H),
0.86 (td, 1H, J¼11.5, 10.5, 3.1 Hz), 0.88 (m, 1H), 1.10 (qt,
1H, J¼11.5, 3.3 Hz), 1.22 (qt, 1H, J¼11.5, 3.1 Hz), 1.28
(qd, 1H, J¼11.5, 3.1 Hz), 1.52 (dq, 1H, J¼12.5, 3.6,
3.3 Hz), 1.55 (qt, 1H, J¼10.5, 3.6 Hz), 1.62 (m, 1H), 1.69
(m, 1H), 1.81 (dq, 1H, J¼11.5, 3.1 Hz), 2.00 (dd, 1H,
J¼13.4, 10.5 Hz), 2.94 (dd, 1H, J¼13.4, 3.6 Hz), 6.94 (m,
2H), 7.14 (m, 1H), 7.21 (m, 2H), 7.37 (m, 3H), 7.58 (m,
2H); 13C NMR (CDCl3, 125 MHz) d: ꢁ3.06, ꢁ2.24,
25.88, 27.69, 28.26, 30.80, 32.63, 40.85, 43.26, 125.37,
127.63 (2C), 127.86 (2C), 128.53, 128.90 (2C), 133.67
(2C), 139.81, 141.48; IR (film): 699, 733, 768, 831, 1051,
1063, 1114, 1251, 1427, 1588, 1603, 2850, 2927, 3024,
3067 cmꢁ1; MS (+CI) m/z (%): 135.0 (18), 217.0 (10),
231.0 (100), 293.1 (39), 307.1 (5), 309.2 (2, M++1);
HRMS (CI) calculated for C21H28Si: 308.1960, found:
308.1955.
5.6.1. Compound 10a. [a]2D0 +22.3 (c 1.0, EtOH), viscous
oil, 88%; [a]2D0 –18 (c 1.0, EtOH), viscous oil, 90%.
1H NMR (CDCl3, 500 MHz) d: ꢁ0.11 (s, 3H), ꢁ0.06 (s, 3H),
1.66 (m, 1H), 1.88 (m, 3H), 2.03 (m, 1H), 2.15 (m, 1H),
2.65 (m, 1H), 3.36 (d, 1H, J¼3.1 Hz), 3.21–3.33 (m, 4H),
7.13–7.43 (m, 10H); 13C NMR (CDCl3, 125 MHz) d:
ꢁ5.05, ꢁ4.49, 20.40, 26.29, 30.25, 38.05, 38.48, 39.14,
55.55, 74.44, 126.92, 127.37 (2C), 127.54 (2C), 128.52,
130.69 (2C), 133.70 (2C), 138.10, 142.46; IR (film): 770,
812, 836, 1111, 1248, 1245, 1426, 1494, 1599, 2854,
2923, 3024, 3066 cmꢁ1; MS (+CI) m/z (%): 124.8 (100),
135.1 (10), 248.9 (48), 369.0 (13), 385.2 (16, M++1);
HRMS (CI) calculated for C22H28S2Si: 384.1401, found:
384.1396.
5.5.9. trans-1-(Dimethylphenylsilyl)-2-(2-naphthyl-
methyl)-cyclohexane 8b. (1S,2R)-8b: 34%, viscous oil,
[a]2D0 +33 (c 0.41, EtOH); (1R,2S)-8b: 38%, viscous oil,
[a]2D0 ꢁ35 (c 0.4, EtOH).
1H NMR (CDCl3, 500 MHz) d: 13C NMR (CDCl3,
125 MHz): ꢁ2.95, ꢁ2.14, 25.84, 27.69, 28.32, 30.85,
32.73, 40.82, 43.35, 124.83, 125.62, 127.05, 127.23,
127.33, 127.42, 127.62, 127.7 (2C), 128.61, 131.74,
133.31, 133.75 (2C), 139.01, 139.77; IR (film): 831, 1112,
1248, 1426, 1444, 1600, 2849, 2925, 3049 cmꢁ1; MS
(+CI) m/z (%): 127.1 (23), 135.0 (13), 141.1 (24), 281.1
(100), 343.2 (16), 358.0 (4, M+), 359.1 (2, M++1); HRMS
(CI) calculated for C25H30Si: 358.2117, found: 358.2112.
5.6.2. Compound 10b. [a]D20 +28 (c 0.8, EtOH), viscous oil,
47%; [a]2D0 ꢁ25 (c 0.8, EtOH), viscous oil, 50%.
1H NMR (CDCl3, 200 MHz) d: ꢁ0.26 (s, 3H), ꢁ0.25 (s, 3H),
1.26–1.34 (m, 1H), 1.60–1.72 (m, 2H), 2.02–2.17 (m, 2H),
2.68–2.99 (m, 2H), 3.09–3.16 (m, 2H), 3.34–3.42 (m, 2H),
4.42 (d, 1H, J¼3.2 Hz), 7.05 (dd, 1H, J¼7.9, 1.5 Hz),
7.11–7.45 (m, 7H), 7.72–7.90 (m, 4H); 13C NMR (CDCl3,
50 MHz) d: ꢁ4.26, ꢁ4.12, 20.88, 26.51, 30.43, 38.00,
38.63, 39.47, 45.87, 74.85, 124.48, 124.87, 124.94,
125.40, 126.69, 127.47 (2C), 127.80, 128.51, 128.71,
133.49, 133.65 (2C), 133.82, 138.18, 139.49; IR (film) in
cmꢁ1: 779, 797, 834, 1117, 1255, 1427, 1488, 1597, 2859,
2928, 3049, 3067; MS (+CI) m/z (%): 58.9 (100), 74.9
(60), 135.0 (17), 136.8 (19), 207.1 (64), 299.2 (37), 419.2
(10), 434.2 (10, M+), 435.3 (10, M++1).
5.5.10. trans-1-(Dimethylphenylsilyl)-2-(1-naphthyl-
methyl)-cyclohexane 8c. (1S,2R)-8c: 31%, viscous oil,
[a]2D0 +45 (c 0.75, EtOH); (1R,2S)-8c: 33%, viscous oil,
[a]2D0 ꢁ44 (c 0.7, EtOH).
1H NMR (CDCl3, 500 MHz) d: 0.44 (s, 3H), 0.48 (s, 3H),
0.93 (m, 2H), 1.07 (qt, 1H, J¼12.3, 3.6 Hz), 1.26 (m, 2H),
1.42 (m, 1H), 1.59 (m, 1H), 1.69 (m, 1H), 1.84 (m, 1H),
1.93 (m, 1H), 2.51 (dd, 1H, J¼11.3, 14.4 Hz), 3.37 (dd,
1H, J¼14.4, 4.1 Hz), 7.13 (d, 1H, J¼7.0 Hz), 7.29 (m,
1H), 7.34 (t, 1H, J¼7.3 Hz), 7.42 (m, 4H), 7.47 (d, 1H,
J¼8.5 Hz), 7.65 (dd, 2H, J¼7.3, 1.6 Hz), 7.67 (d, 1H,
J¼8.0 Hz), 7.80 (d, 1H, J¼8.1 Hz); 13C NMR (CDCl3,
125 MHz): ꢁ2.35, ꢁ1.83, 25.75, 27.71, 28.26, 32.30,
32.89, 39.57, 40.37, 124.17, 125.01, 125.02, 125.27,
126.19, 127.07, 127.82 (2C), 128.37, 128.71, 132.08,
5.7. Synthesis of cis-2-arylmethyl-1-dialkylphenylsilyl
cycloalkanones 9a,b
General procedure: to a solution of 0.45 g (1.17 mmol,
1.0 equiv) (ꢁ)-10a in 5 mL MeOH, an excess of Raney
nickel was added (10-fold). The reaction mixture was stirred

Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
8461
at room temperature for 10 h (TLC check). The mixture was
Acknowledgements
This work was generously supported by Rhodia and the Uni-
filtered through a pad of Celite and washed with CH2Cl2. The
filtrate was extracted with 3ꢃ5 mL CH2Cl2. The organic
layer was dried, filtered and concentrated. Flash chromato-
graphy of the residue (Rf¼0.45, hexane) afforded 0.21 g
(60%) product (ꢁ)-9a as viscous oil.
ꢀ
versite catholique de Louvain. We thank Dr. R. Touillaux for
NMR analyses. G.D. is research associate of the FRS-FNRS,
Brussels. We wish also to acknowledge financial support
from the Belgian Program on Interuniversity Poles of Attrac-
tion (IAP no P5/33). We thank Dr. Loic Guillonneau for his
help with the preparation of the manuscript.
5.7.1. cis-1-(Dimethylphenylsilyl)-2-phenyl-cyclohexane
11a. (+)-9a: [a]2D0 +24 (c 1.0, EtOH), viscous oil, 58%;
(ꢁ)-9a: [a]2D0 ꢁ25.6 (c 1.0, EtOH), viscous oil, 60%.
1H NMR (CDCl3, 200 MHz) d: ꢁ0.20 (s, 3H), 0.09 (s, 3H),
1.42–1.70 (m, 5H), 1.71–1.81 (m, 4H), 2.99–3.04 (m, 1H),
7.14–7.26 (m, 5H), 7.27–7.48 (m, 5H); 13C NMR (CDCl3,
50 MHz) d: ꢁ2.40, ꢁ1.87, 24.54, 25.85, 27.31, 30.94,
32.17, 43.83, 125.86, 127.39 (2C), 127.83 (2C), 128.18
(2C), 128.37, 133.80 (2C), 139.99, 146.41; IR (film) in:
814, 834, 1112, 1249, 1427, 1446, 1600, 2848, 2923, 3025,
3066 cmꢁ1, MS (+CI) m/z (%): 135.1 (4), 217.2 (30), 279.2
(100), 293.2 (28), 294.0 (24, 295.1 (8, M++1); HRMS (CI)
calculated for C20H26Si: 294.1803, found: 294.1796.
References and notes
1. (a) Ghosez, L. Stereocontrolled Organic Synthesis; Trost, B.,
Ed.; Blackwell Scientific: Oxford, 1994; p 193; (b) Mbiya,
ꢀ
K. Dissertation, Universite catholique de Louvain, Belgium,
1994.
2. (a) Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617–
2618; (b) Ntirampebura, D.; Ghosez, L. Tetrahedron Lett.
1999, 40, 7079–7082; Synthesis 2002, 2043–2052; (c)
Johnson, J. S.; Evans, D. A. Acc. Chem. Res. 2000, 33,
325–335.
ꢀ
3. Happaerts, T. Dissertation, Universite catholique de Louvain,
Belgium, 2002.
4. (a) Lamy-Schelkens, H.; Giomi, D.; Ghosez, L. Tetrahedron
Lett. 1989, 30, 5887–5890; (b) Lamy-Schelkens, H.; Ghosez,
L. Tetrahedron Lett. 1989, 30, 5891–5894.
5. Mathieu, B.; Ghosez, L. Tetrahedron Lett. 1997, 38, 5497–
5500.
6. Ishii, A.; Kotera, O.; Saeki, T.; Mikami, K. Synlett 1997, 1145.
7. Mathieu, B.; de Fays, L.; Ghosez, L. Tetrahedron Lett. 2000,
41, 9561–9564.
8. Examples: Berry, M. B.; Griffiths, R. J.; Yufit, D. S.; Steel, P. G.
Chem. Commun. 1998, 2155–2156; Kuhnert, N.; Peverley, J.;
Robertson, J. Tetrahedron Lett. 1998, 39, 3215–3216;
Othman, R. B.; Bousquet, T.; Othman, M.; Dalla, V. Org.
Lett. 2005, 7, 5335–5337; Hara, K.; Akiyama, R.; Sawamura,
M. Org. Lett. 2005, 7, 5621–5623; Ishihara, K.; Hiraiwa, Y.;
Yamamoto, H. Synlett 2001, 1851–1854.
5.7.2. cis-1-(Dimethylphenylsilyl)-2-(1-naphthyl)-cyclo-
hexane 9b. (+)-9b: [a]2D0 +30 (c 0.6, EtOH), viscous oil,
19%; (ꢁ)-9b: [a]2D0 ꢁ31 (c 0.5, EtOH), viscous oil, 20%.
1H NMR (CDCl3, 200 MHz) d: ꢁ0.41 (s, 3H), 0.12 (s, 3H),
1.40–1.70 (m, 4H), 1.71–2.10 (m, 5H), 3.70–3.80 (m, 1H),
7.11–7.26 (m, 4H), 7.34–7.53 (m, 5H), 7.63–7.68 (dd,
1H, J¼6.0, 1.9 Hz), 7.78–7.80 (m, 1H), 8.04 (d, 1H,
J¼7.8 Hz); 13C NMR (CDCl3, 50 MHz) d: ꢁ4.10, ꢁ0.87,
25.48, 26.85, 28.00, 30.98, 32.27, 42.81, 122.92, 124.86,
125.00, 125.46, 125.84, 126.48, 127.48 (2C), 128.88,
128.98, 131.05, 133.86 (2C), 133.99, 139.04, 143.78; IR
(film): 776, 817, 834, 1112, 1248, 1444, 1596, 2848, 2924,
3046, 3067 cmꢁ1; MS (+CI) m/z (%): 135.1 (3), 267.2
(86), 295.2 (14), 329.2 (72), 344.2 (100, M+), 345.3 (28,
M++1); HRMS (CI) calculated for C24H28Si: 344.1960,
found: 344.1954.
9. Desmurs, J. R.; Ghosez, L.; Martins, J.; Deforth, T.; Mignani,
G. J. Organomet. Chem. 2002, 646, 171–178.
10. Johannsen, M.; Jorgensen, K. A.; Helmchen, G. A. J. Am.
Chem. Soc. 1998, 120, 7637–7638.
5.8. General procedure for in situ preparation of sily-
lated triflimides and catalysed Diels–Alder reactions
To a 25 ml two-neck flask equipped with a tube of silica
gel and a stirring bar, under argon were added 15 mol %
ENP dialkylphenylsilyl-cycloalkane (1 equiv) and enough
dry CH2Cl2 [solvent/diene¼3:1 (v/v)]. A solution of bis-
(trifluoromethanesulfonyl)imide (10 mol %) in CH2Cl2
was added at room temperature and the reaction continued
for 2–3 h. 2,6-Di(tert-butyl)-4-methylpyridine (20 mol %,
DTBMP, dissolved in CH2Cl2) was added and the mixture
cooled to the temperature mentioned in the table. Methyl
acrylate (1 equiv) was added and followed by cyclopenta-
diene (4 equiv) 15 min later. The reaction mixture was
stirred for 1.5 h (checked by 1H NMR) and quenched
with 3 mL saturated NaHCO3 aqueous solution. The mix-
ture was extracted with 3ꢃ10 mL CH2Cl2, and the com-
bined organic phases were dried, filtered and evaporated.
The products were isolated by flash chromatography
(yields, see Table 5). Enantiomeric excesses were deter-
mined by chiral GC. Conversions and ratio of endo/exo
11. (a) Shirakawa, S.; Lombardi, P. J.; Leighton, J. L. J. Am.
Chem. Soc. 2005, 127, 9974–9975; (b) Kubota, K.; Hamblett,
C. L.; Wang, X.; Leighton, J. L. Tetrahedron 2006, 62,
11397–11401.
12. (a) Hawkins, J. M.; Loren, S. J. Am. Chem. Soc. 1991, 113,
7794–7795; (b) Hawkins, J. M.; Loren, S. J. Am. Chem. Soc.
1994, 116, 1657–1660; (c) Hawkins, J. M.; Nambu, N.;
Loren, S. Org. Lett. 2003, 5, 4293–4295.
13. Honma, T.; Nakajo, M.; Mizugaki, T.; Ebitani, K.; Kaneda, K.
Tetrahedron Lett. 2002, 43, 6229–6232.
14. (a) Corey, E. J.; Melvin, L. S.; Haslanger, M. F. Tetrahedron
Lett. 1975, 36, 3117–3120; (b) Fuchs, P. L. J. Org. Chem.
1976, 41, 2935–2937; (c) Stork, G.; Ponaras, A. A. J. Org.
Chem. 1976, 41, 2937–2939; (d) Wender, P. A.; Erhardt,
J. M.; Letendre, L. J. J. Am. Chem. Soc. 1981, 103, 2114–2116.
15. Solladie, G.; Hutt, J. J. Org. Chem. 1987, 52, 3560–3566.
16. Jean, K. Y.; Cava, M. P. J. Org. Chem. 1983, 48, 1449–1451.
17. Rivaka, B. S.; David, G. J. Chem. Soc. 1957, 1289.
18. (a) Ager, D. J.; Fleming, I. J. Chem. Soc., Chem. Commun.
1978, 177–178; (b) Ager, D. J.; Fleming, I.; Patel, S. K.
1
were measured by H NMR on the crude product (endo/
exo also by chiral GC).

8462
Z. Tang et al. / Tetrahedron 63 (2007) 8449–8462
J. Chem. Soc., Perkin Trans. 1 1981, 2520–2526; (c) Mathieu,
ꢀ
B. Ph.D. Dissertation, Universite catholique de Louvain,
23. Kim, S.; Chang, H. O.; Ko, J. S.; Ahn, K. H.; Kim, Y. J. J. Org.
Chem. 1985, 50, 1927–1932.
Belgium, 2001.
19. Hatzigrigoriou, E.; Wartski, L.; Seyden-Penne, J.; Toromanoff,
E. Tetrahedron 1985, 41, 5045–5050.
20. Pretsch, E.; Clercq, T.; Seibl, N.; Simon, W. Table of Spectral
Data For Structure Determination of Organic Compounds, 2nd
ed.; Springer: Berlin, Heidelberg, 1989.
21. Engel, W.; Fleming, I.; Smithers, R. H. J. Chem. Soc., Perkin
Trans. 1 1986, 1637–1641.
22. Crystallographic data have been deposited with the Cambridge
Crystallographic Data Centre and allocated deposition num-
bers CCDC 642125–642127.
24. Kumar, V.; Dev, S. Tetrahedron Lett. 1983, 24, 1289–1292.
25. Rao Narasimha, P. J. Org. Chem. 1971, 36, 2426–2434.
26. Mathieu, B.; Ghosez, L. Tetrahedron 2002, 58, 8219–8226.
27. Loncharich, R. J.; Schwarz, T. R.; Houk, K. N. J. Am. Chem.
Soc. 1987, 109, 5502–5503.
28. DFT (density functional theory) B3LYP calculations. The func-
tion basis set is the double zeta 6-31G* with one shell of d
orbitals on the second row atoms. All degrees of freedom of
themoleculargeometry(distances,bondangles,dihedralangles)
were completely optimised by minimisation of the partial
gradient under the threshold of 15 10-6 Hartree/Bohr-radian.