Asymmetric Diels-Alder reactions of N-sulfinyl dienophiles using chiral Ti(IV) Lewis acids

Article abstract of DOI:10.1016/S0957-4166(02)00661-4

Enantioselective hetero Diels-Alder (HDA) reactions of 1,3-cyclohexadiene with benzyl N-sulfinylcarbamate 1a and with N-sulfinyl-p-toluensulfonamide 1b promoted by chiral Ti(IV)-based Lewis acids are reported. The obtained yields and enantiomeric excesses obtained are heavily dependant on the mode of catalyst preparation. Acceptable reproducibility was obtained with Ti(IV)-catalysts prepared from Me₂TiCl₂ and chiral diols. Testing of various chiral diols gave the endo adduct in yields of up to 69% with 76% ee. The absolute configuration of the HDA products were established by chemical correlation and verified by X-ray crystallography.

Full text of DOI:10.1016/S0957-4166(02)00661-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2407–2415
Asymmetric Diels–Alder reactions of N-sulfinyl dienophiles using
chiral Ti(IV) Lewis acids
Annette Bayer,a Lars K. Hansena and Odd R. Gautunb,*
aDepartment of Chemistry, Faculty of Science, University of Tromsø, NO-9037 Tromsø, Norway
bDepartment of Chemistry, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway
Received 28 May 2002; revised 14 October 2002; accepted 16 October 2002
Abstract—Enantioselective hetero Diels–Alder (HDA) reactions of 1,3-cyclohexadiene with benzyl N-sulfinylcarbamate 1a and
with N-sulfinyl-p-toluensulfonamide 1b promoted by chiral Ti(IV)-based Lewis acids are reported. The obtained yields and
enantiomeric excesses obtained are heavily dependant on the mode of catalyst preparation. Acceptable reproducibility was
obtained with Ti(IV)-catalysts prepared from Me2TiCl2 and chiral diols. Testing of various chiral diols gave the endo adduct in
yields of up to 69% with 76% ee. The absolute configuration of the HDA products were established by chemical correlation and
verified by X-ray crystallography. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
HDA reactions of N-sulfinyl compounds 1a13a and 1b3
with 1,3-cyclohexadiene (see Fig. 1). In our initial stud-
ies, the yields and reproducibilities of the reactions were
found to depend strongly on the mode of catalyst
preparation. These findings are discussed herein. The
relative and absolute configuration of the obtained
adducts 2a and 2b, respectively, are confirmed by X-ray
analysis.
The Diels–Alder (DA) and hetero Diels–Alder (HDA)
reactions constitute an extremely useful set of reactions,
particularly for stereoselective synthesis. Since we are
studying reactions for the stereoselective introduction
of nitrogen into organic compounds, HDA reactions
using N-sulfinyl compounds as dienophiles caught our
interest.1–8 This reaction affords 1,2-thiazine 1-oxides,
which are precursors for unsaturated, vicinal amino-
alcohols and homoallylic amines,7 and have found
application in the total synthesis of natural products9
and biologically active compounds, e.g. agelastatin A,10
cylindrospermopsin and 7-epicylindrospermopsin,11 5-
epi-desoamine,12 threo- and erythro-sphingosine,13 ben-
zodiazepines and benzothiadiazepines.14 Only a few
examples of asymmetric HDA reactions using either
chiral N-sulfinyl dienophiles15,16 or chiral dienes17 have
been reported to proceed with high diastereoselectivities
(>97%). The application of chiral Lewis acid complexes
as catalysts for DA and HDA reactions has been
demonstrated to give excellent chiral induction for
many different reaction systems.18–20 Recently, we
reported briefly on the use of chiral Ti(IV),21 Cu(II) and
Zn(II) complexes22 as promoters for asymmetric HDA
reactions using N-sulfinyl dienophiles. Herein, we
present a more detailed report on the Ti(IV)-promoted
2. Results and discussion
2.1. Preparation of the catalyst
The synthesis and use of chiral titanium complexes has
been reviewed by several authors.23,24 Initially, we pre-
pared [TiCl2(3b-ate)] in situ by exchanging the alcohol
ligands of TiCl2(OiPr)2 with diol 3b, followed by
removal of 2-propanol by azeotropic distillation or by
absorption onto molecular sieves according to the
method of Narasaka et al.25 The reactions completed
with the catalysts prepared by these procedures gave
low yields (Table 1, entries 1 and 2). We also experi-
enced great difficulties in obtaining reproducible results.
Studies of these catalysts by 1H NMR showed the
presence of free 2-propanol. Alcoholysis of the N-sulfi-
nyl compound 1a may explain the low and non-repro-
ducible yields. The insufficient removal of the alcohol
may be due to coordination to titanium.23,26 Unfortu-
nately, attempts to prepare the catalyst by alcohol
exchange of Ti(OiPr)4 with 3b, followed by treatment
* Corresponding author. Tel.: 47 73 59 41 01; fax: 47 73 59 42 56;
e-mail: odd.gautun@chembio.ntnu.no
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00661-4

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A. Bayer et al. / Tetrahedron: Asymmetry 13 (2002) 2407–2415
Figure 1. Asymmetric Diels–Alder reactions of N-sulfinyl dienophiles 1a and 1b with 1,3-cyclohexadiene promoted by chiral
Ti(IV) Lewis acids.
Table 1. HDA reactions of 1a and 1,3-cyclohexadiene at −70°C with [TiCl2(3b-ate)] (100 mol%) prepared by different
methods
Entry
Method
Solvent (tol.–CH2Cl2)
Yielda /%
endo: exob (% ee)c
Config. of endo-2a
1
2
3
4
5
TiCl2(OiPr)2 (azeotr.)25
6:1
6:1
6:1
6:1
6:1
24
0
45
44
70
\95 (57):5
–
\95 (43):5
\95 (0):5
\95 (58):5
1R,2S,4S
–
1R,2S,4S
–
1R,2S,4S
25
,
TiCl2(OiPr)2 (4 A MS)
27
1. Ti(OiPr)4; 2. SiCl4
28
1. BuLi; 2. TiCl4
Me2TiCl2
a Isolated yield of endo- and exo-2a.
b Determined by 1H NMR (400 MHz) on crude product.
c Determined by HPLC analysis using DAICEL Chiracel OJ (2-propanol/n-hexane, 35:65; 0.5 ml/min).
27
with SiCl4 (entry 3) or by ligand exchange of TiCl4
with deprotonated 3b28 (entry 4) did not improve the
results sufficiently. Thus, we developed a new method
for preparation of the catalyst using the thermally labile
coordinated isopropanol in complexes prepared from
Me2TiCl2. The broadening of the signals corresponding
to [TiCl2(3b-ate)] indicates the formation of aggregates
(Fig. 2a). When isopropanol was added (Fig. 2b), these
lines sharpened, probably due to coordination of the
alcohol to complex [TiCl2(3b-ate)], and the spectrum
became similar to that reported by Iwasawa et al.30 (see
Fig. 2c). The 1H NMR spectrum also showed that
impurities were present in the catalyst solution prepared
from Me2TiCl2. These impurities were not identified
29
Me2TiCl2 as a titanium precursor. The reactions
between Me2TiCl2 and the diol were expected to give
methane as a by-product, which should not cause prob-
lems in the subsequent HDA reactions. Indeed, catalyst
solutions prepared in this manner lead to improved and
more reproducible results with respect to yield and ee
(entry 5). However, minor variations were observed for
different catalyst batches (49–58% ee and 60–70%
yields).
and catalytically active species different from
a
[TiCl2(3b-ate)] complex cannot be excluded.
The relationship between the enantiomeric purity of the
chiral ligand and the ee of the product was investigated
for the HDA test reaction. Stoichiometric amounts of
the catalyst were used in this study. The results are
plotted in Fig. 3. A positive nonlinear effect (NLE) was
found. The deviation from linearity indicated that
diastereomeric species were formed.31 Moreover, the
The complex formed in the reaction of diol 3b and
1
Me2TiCl2 was analyzed by H NMR spectroscopy (Fig.
2). The ratio of complexed to uncomplexed diol 3b in
the catalyst solution was determined to be ca. 95:5. The
1H NMR spectrum differs from earlier reports.30 Some
of the differences may be explained by the absence of

A. Bayer et al. / Tetrahedron: Asymmetry 13 (2002) 2407–2415
2409
1
Figure 2. Expansions of H NMR spectra of the catalyst prepared from (a) Me2TiCl2 (b) Me2TiCl2 after addition of 2-PrOH (0.4
equiv.) and (c) TiCl2(OiPr)2.
Figure 3. Nonlinear effect in the HDA reaction of 1a with 1,3-cyclohexadiene promoted by [TiCl2(3b-ate)] (100 mol%) of various
enantiomeric purities.
homochiral species giving enantiomeric enrichment
was more active than the heterochiral species giving
racemic products. When scalemic mixtures of the cat-
alyst were prepared a precipitate was formed. This is
in agreement with observations reported by Iwasawa
et al. who also found positive NLE effects for
[TiCl2(3b-ate)] mediated DA reactions and precipita-
tion of racemic diol.30

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A. Bayer et al. / Tetrahedron: Asymmetry 13 (2002) 2407–2415
2.2. Reaction conditions, ligands and counterions
(entries 7, 8, 15 and 16). For these ligands even the
diastereoselectivity, which remained high for all six-
and seven-membered titanacycles, decreased. In some
cases (diols 5–7) a precipitate formed during prepara-
tion of the catalyst, which may explain the poor yields
obtained with these ligands. The apparent inactivity of
the catalyst obtained with ligand 9 may be ascribed to
the additional coordination sites of the ligand.
The chiral diols 3a,32 3b,25 3c,33 4,34 5,35 6,36 7,37 8 and
938 were tested as ligands for the titanium(IV)-pro-
moted HDA reactions of N-sufinyl dienophiles 1a and
1b with 1,3-cyclohexadiene (Fig. 1). The results are
given in Table 2. The minimum amount of catalyst
necessary for good results to be obtained was found to
be 30 mol%. With catalyst loading of 10 mol%, 1a a
dramatic decrease in the yield was observed, although
the ee and de were unaffected. For 1b the ee and de
decreased due to a pronounced background reaction,
but the yield was not reduced significantly. The data
given in Table 2 were obtained with stoichiometric
amounts of catalyst relative to the N-sulfinyl com-
pounds. Generally, the HDA reactions were carried out
at −70°C (1a) or −85°C (1b) in toluene with CH2Cl2 as
cosolvent. The yields were found to increase with the
reaction time, 5 h giving around 20% yield and 15–20 h
giving up to 86% yield. Prolonging the reaction times
beyond 20 h did not lead to further improvement in the
yields.
The complexes obtained by exchange of chlorides of
[TiCl2(3b-ate)] with triflates and tosylates39 did not
promote the HDA reaction.
2.3. Stereochemical proof
The relative configuration (endo/exo) of the cycload-
ducts 2a and 2b was determined by considering the
shielding effect of the ‘SꢀO’ group in the 1H NMR
spectra, similar to the work described by Zhang and
Flann.40 In the endo configuration the protons at the 7-
and 8-positions are unaffected by the SꢀO bond (1.76–
1.12 ppm), while in the exo configuration these protons
are significantly less shielded (2.83–1.44 ppm). X-Ray
analysis of the major isomers confirmed an endo
configuration at sulfur. X-Ray crystal structures of
endo-2a and (1R,2S,4S)-2b are shown in Figs. 4 and 5,
respectively.41
The best results with respect to stereoselectivity were
obtained with diol 4 (2a: >90% de, 76% ee (entry 4); 2b:
82% de, 74% ee (entry 13)). The yields were comparable
(2a: 69%) or somewhat lower (2b: 58%) than those seen
with the diol 3b (2a: 70%; 2b: 83%). The ligands 3a–c
and 4 induced stereoselectivity in the same sense, (R)-
ligands giving (1R,2S,4S)-2a as the major isomer. Inter-
estingly, a switch of enantioselectivity was observed
when changing from N-sulfinyl dienophiles 1a (X=
Cbz) to 1b (X=Ts). For 1b the (R)-ligands gave
(1S,2R,4R)-2b. In all cases, the major diastereomer
resulted from an endo approach of the reagents. It
seemed that the ligands leading to five-membered
titanacycles gave lower stereoselectivities and yields
For compound 2a the X-ray structure shown in Fig. 4
gave the relative configuration. For 2b the absolute
configuration was also assigned. In both cases the
X-ray showed conglomerate crystals. These observa-
tions were also confirmed by chiral HPLC analysis.
Absolute configuration of the endo isomer of 2a (X=
Cbz) was established by chemical correlation with the
known cyclic carbamate (1R,2S)-13 following Wein-
reb’s method16 (Scheme 1).
Table 2. HDA reactions of N-sulfinyl compounds 1a and 1b with 1,3-cyclohexadiene promoted by the complexes obtained
from Me2TiCl2 and the chiral ligand (100 mol%)
Entry
N-sulf.
Ligand
Solvent (tol.–CH2Cl2)
Temp/°C (time/h)
Yielda/%
endo:exob (% ee)c Config. of endo-2
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1b
3a
3b
3c
4
5
6
7
8
9
3a
3b
3c
4
6
7
1:1
6:1
8:1
6:1
9:1
1:6
5:2
6:1
1:1
1:1
6:1
6:1
6:1
1:6
2:1
6:1
−55 (20)
−70 (22)
−70 (20)
−68 (18)
−70 (21)
−68 (18)
−42 (16)
−42 (16)
−70 (20)
−85 (16)
−85 (17)
−85 (16)
−85 (17)
−85 (17)
−85 (16)
−85 (16)
63
70
69
69
11
0
32
35
0
63
83
68
58
38
29
42
\95 (40):5
\95 (58):5
92 (37):8
\95 (76):5
\95 (48):5
–
75 (13):25 (35)
80 (13):20
–
1R,2S,4S
1R,2S,4S
1R,2S,4S
1S,2R,4R
1R,2S,4S
–
1R,2S,4S
1R,2S,4S
–
1S,2R,4R
1S,2R,4R
1S,2R,4R
1R,2S,4S
–
9
10
11
12
13
14
15
16
92 (59):8
94 (69):6 (22)
50 (37):50 (25)
91 (74):9 (30)
76 (0):24 (0)
82 (15):18 (0)
80 (36):20 (43)
1R,2S,4S
1R,2S,4S
8
a Isolated yield of endo- and exo-2. Generally, the total isolated yield of HDA product and the amine corresponding to the N-sulfinyl compound
accounted for >80% of the limiting starting material (N-sulfinyl compound).
b Determined by 1H NMR (400 MHz) on crude product.
c Determined by HPLC analysis using DAICEL Chiracel OJ (2-propanol/n-hexane, 35:65; 0.5 ml/min) for 2a (X=Cbz) and DAICEL Chiralpak
AD (2-propanol/n-hexane, 20:80; 1.0 ml/min) for 2b (X=Ts).

A. Bayer et al. / Tetrahedron: Asymmetry 13 (2002) 2407–2415
2411
Figure 4. X-Ray crystal structure of endo-2a.
Figure 5. X-Ray crystal structure of (1R,2S,4S)-2b (entry 13,
Table 2).
The endo-2a obtained in entry 2 (Table 2) was rear-
ranged to hydroxy carbamate 11 and then cyclized to
carbamate 12. Catalytic hydrogenation of 12 provided
(1R,1S)-1316 and thus endo-2a (entry 2, Table 2) had
the (1R,2S,4S)-configuration. The absolute configura-
tion of compound endo-2b (X=Ts) was determined by
chemical correlation with endo-2a (X=Cbz) as depicted
in Scheme 2.
Perkin–Elmer 241 Polarimeter. Enantiomeric excesses
were determined by HPLC analysis, using Daicels
columns Chiracel OD-H and OJ and Chiralpak AD
(250×4.6 mm). 1H (400 MHz) and 13C (100 MHz)
spectra were obtained on a JEOL JNM-EX 400 FT
spectrometer using CDCl3 as solvent and internal stan-
1
dard (reference values 7.25 and 77.1 for H and 13C,
The HDA adduct (1R,2S,4S)-2a was rearranged to
carbamate (S)-14a followed by deprotection and tosyla-
tion to yield tosylate (S)-14b. Compound endo-2b
(entry 11, Table 2) was rearranged to tosylate (R)-14b,
correspondingly. Comparison of the tosylates 14b by
HPLC showed that endo-2b had the (1S,2R,4R)-
configuration. This result was verified by X-ray crystal-
lography (Fig. 5).41
respectively). IR spectra were run on a Perkin–Elmer
1600 FT-IR instrument, and only the strongest/struc-
turally most important peaks are listed. The mass spec-
tra were recorded on a Finnigan MAT 95XL mass
spectrometer, and a VG Quattro quadrupole mass spec-
trometer connected to a Hewlett Packard 5890 II gas
chromatograph, equipped with an unpolar CP-Sil 5CB-
MS capillary column (30 m×0.25 mm i.d., film thick-
ness 0.25 mm). The ionization potential was 70 eV and
the temperature in the ion source was 180°C. The
elemental analysis were performed at the Department
of Organic Chemical Technology, Prague, Czech
Republic. Compounds 1a,13a 1b,3 3a,32 3b,25 3c,33 4,34
5,35 6,36 737 and 938 were prepared according to litera-
ture procedures. The chiral diol 8 was purchased from
Fluka. Tetrahydrofuran (THF) was distilled under
nitrogen from Na/benzophenone. Acetonitrile and
methylene chloride were distilled under nitrogen from
3. Experimental
3.1. General remarks
Melting points were determined on a Buchi 535 appara-
tus and are uncorrected. TLC was performed on Merck
silica gel 60 F254 plates, using UV light at 254 nm and
a 5% alcoholic molybdophosphoric acid for detection.
Silica gel for flash chromatography was purchased from
Grace-Amicon. Optical rotations were measured with a
,
calcium hydride and stored over molecular sieves (3 A).
Scheme 1. Reagents and conditions: (a) PhMgBr, THF, −60°C, 0.5 h, 88%; (b) P(OMe)3, MeOH, 80°C, 93%; (c) t-BuOK, THF,
0°C, 1 h, 79%; (d) 5% Rh–Al2O3, 1 atm H2, EtOAc:n-hexane (1:2), rt, 21 h, 47%.

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A. Bayer et al. / Tetrahedron: Asymmetry 13 (2002) 2407–2415
Scheme 2. Reagents and conditions: (a) (i) 1.25 M aq. NaOH, rt, 14 h; (ii) 0.5 M aq HCl, 0°C, 10 min, 75% (Cbz), 34% (Ts); (b)
(i) TMSI, MeCN, 0°C, 30 min; MeOH, rt, 10 min; (ii) TsCl, Et3N, CH2Cl2, rt, 21 h, 77%.
3.2. Catalyst preparation
catalyst mixture (2.7 ml, 0.4 mmol) was stirred for 10
min at rt and then cooled to −70°C. The N-sulfinylcar-
bamate 1a (1 M in CHCl2, 400 ml, 0.4 mmol) was added
and the mixture stirred for 10 min before 1,3-cyclohexa-
diene (100 ml, 1.0 mmol) was added slowly along the
wall of the flask. After stirring at −70°C for 20 h, the
reaction mixture was hydrolyzed and worked up as
described above. The HDA products 2a were analyzed
by HPLC (Chiracel OJ; 2-propanol/n-hexane, 35:65;
0.5 ml min−1; UV detector, 230 nm). The results are
shown in Fig. 3.
In general, the chiral catalyst was prepared by mixing
29
Me2TiCl2 (approximately 5.0 mmol) and a solution of
the chiral diols 3a–c, 4, 5 or 8 (5.0 mmol) in dry toluene
(15 ml) under argon atm at −75°C. For ligand 6 dry
dichloromethane was used as solvent and ligands 7 and
9 were dissolved in toluene/dichloromethane, (4:1) and
(3:2), respectively. The resulting solution was then
allowed to reach rt and thereafter diluted with toluene
or dichloromethane (ca. 0.2 M, quantitative yield was
assumed). This solution was stored in the freezer
(−20°C) in a sealed flask for up to 1 month without
detectable deterioration.
3.4.1. Benzyl (1R,2S,4S)-2l4-thia-3-azabicyclo[2.2.2]oct-
5-ene-3-carboxylate 2-oxide, (1R,2S,4S)-2a. [h]2D0 +134.6
(c 1.1, CH2Cl2). HPLC analysis (Chiracel OJ; 2-
propanol/n-hexane, 35:65; 0.5 ml min−1; UV detector,
230 nm): 50% ee; rt 27.6 (1R,2S,4S), 32.5 (1S,2R,4R)
min. 1H NMR: 7.40–7.30 (5H, m, Ph), 6.90 (1H, t,
J=7.5 Hz, H-5), 6.32 (1H, t, J=7.3 Hz, H-6), 5.29 (1H,
AB, J=12.5 Hz, Bn), 5.23 (1H, AB, J=12.5 Hz, Bn),
5.17 (1H, br s, H-4), 4.23 (1H, t, J=5.2 Hz, H-1),
1.83–1.70 (2H, m, H-1%/H-4%), 1.63–1.55 (1H, m, H-1%),
1.29–1.19 (1H, m, H-4%). 13C NMR: 154.8 (CꢀO), 136.6
(C-5), 135.5 (1C, Ph), 128.7 (Ph), 128.4 (Ph), 128.0 (Ph),
125.9 (C-6), 68.7 (Bn), 55.7 (C-1), 48.7 (C-4), 24.0
(C-4%), 15.3 (C-1%). IR (KBr): 1717, 1374, 1314, 1297,
1117, 1094. MS: m/z (% rel. int.) 277 (M+, 0.2), 233 (2),
107 (3), 91 (100), 80 (35). Anal. calcd for C14H15NO3S:
C, 60.63; H, 5.45; N, 5.05. Found: C, 60.73; H, 5.45; N,
5.01%. The relative configuration of (1R,2S,4S)-2a was
corroborated by X-ray crystallographic analysis (Fig.
4).41
3.3. General method for the HDA reaction (Table 2)
A typical procedure for the asymmetric HDA reaction
using stoichiometric amounts of the Ti(IV) complex is
given for N-sulfinyl 1a. To a stirred solution of the
chiral Ti(IV) complex (0.4 mmol) in toluene (2 ml) a
solution of 1a (0.4 mmol) in dry dichloromethane (0.34
ml) was added at −70°C and argon atm. After 20 min
a cold solution of 1,3-cyclohexadiene (1.0 mmol) in
toluene (0.4 ml) was added. The reaction mixture was
stirred at −70°C for 20 h and then quenched with
phosphate buffer (2 ml, pH 7). The resultant mixture
was allowed to reach rt, the layers separated, and the
aqueous phase extracted with dichloromethane (3×5 ml,
p.a. quality). The combined organics were dried
(MgSO4), filtered and concentrated in vacuo. The crude
1
product was analyzed by H NMR to determine the
diastereomeric ratio and then purified by flash chro-
matography (ethyl acetate/n-pentane, 1:1). The enan-
tiomeric excess was then determined by chiral HPLC
for each of the separated diastereomers. The results and
further details are given in Table 2.
3.4.2. Benzyl (1R*,2R*,4S*)-2l4-thia-3-azabicyclo-
[2.2.2]oct-5-ene-3-carboxylate 2-oxide, (1R*,2R*,4S*)-
2a. HPLC analysis (Chiracel OJ; 2-propanol/n-hexane,
35:65; 0.5 ml min−1): rt 22.9, 32.6 min. 1H NMR:
7.40–7.30 (5H, m, Ph), 6.80 (1H, t, J=7.3 Hz, H-5),
6.29 (1H, t, J=7.3 Hz, H-6), 5.30 (1H, AB, J=12.5 Hz,
Bn), 5.16 (1H, AB, J=12.5 Hz, Bn), 5.04 (1H, br s,
4-H), 3.97–3.94 (1H, m, 1-H), 2.86–2.80 (1H, m, H-1%),
2.33–2.27 (1H, m, H-4%), 1.57–1.45 (2H, m, H-1%/H-4%).
13C NMR: 155.2 (CꢀO), 140.1 (C-5), 135.5, 128.7,
128.4, 128.0, 127.9, 68.6 (Bn), 56.2 (C-1), 48.3 (C-4),
24.9 (C-4%), 11.4 (C-1%). IR: 1712, 1453, 1383,
3.4. HDA reactions for the investigation of the nonlin-
ear effect
The [TiCl2(3b-ate)] catalyst in different enantiomeric
compositions were prepared by mixing catalyst solu-
tions of [TiCl2(3b-ate)] and [TiCl2(ent-3b-ate)] (ent=
enantiomer; 0.15 M in toluene) under Ar-atm. The

A. Bayer et al. / Tetrahedron: Asymmetry 13 (2002) 2407–2415
2413
1294, 1230, 1113, 1051; MS: m/z (% rel. int.) 278
(M++1, 0.6), 233 (1), 91 (100).
NMR: 7.62–7.54 (2H, m, Ph), 7.54–7.47 (3H, m, Ph),
7.41–7.28 (5H, m, Bn), 6.06 (1H, dd br, J=9.6, 2.2 Hz,
H-2), 5.56 (1H, d br, J=9.6 Hz, H-3), 5.09 (1H, AB,
3.4.3.
(1S,2R,4R)-3-Tosyl-2l4-thia-3-azabicyclo-
J=12.4 Hz, CH2
6
Ph), 5.07 (1H, AB, J=12.4 Hz,
), 4.25 (1H, s br, H-1), 3.32
[2.2.2]oct-5-ene 2-oxide, (1S,2R,4R)-2b. A colorless oil,
which crystallized to a white solid upon standing. [h]D20
−166 (c 1.03, CH2Cl2). HPLC analysis (Chiralpak AD;
2-propanol/n-hexane, 1:4; 1.0 ml min−1; 230 nm): 62%
CH2Ph), 4.94 (1H, d br, NH
6
6
(1H, s br, H-4), 2.13–2.04 (1H, m, H-5), 2.04–1.92 (1H,
m, H-5), 1.75–1.63 (2H, m, H-6). 13C NMR: 155.8
(CꢀO), 141.9, 136.5, 135.9 (C-2), 131.3 (Ph), 129.1
(2×C, Ph), 128.6 (2×C, Bn), 128.2 (Bn), 128.1 (Bn),
124.7 (2×C, Ph), 122.2 (C-3), 66.8 (Bn), 60.2 (C-4), 45.6
(C-1), 26.7 (C-6), 21.1 (C-5). IR (KBr): 3300, 1705,
1525, 1245, 1045. Anal. calcd for C20H21NO3S: C,
67.58; H, 5.95; N, 3.94. Found: C, 67.11; H, 5.76; N,
3.93%. A racemic sample of 10, recrystallized in
CH2Cl2/n-heptane, melted at 96.0–96.2°C.
1
ee; rt 29.2 (1R,2S,4S), 46.2 (1S,2R,4R) min. H NMR:
7.80 and 7.31 (each 2H, AA%BB%, JAB=8.4 Hz, Ts), 6.70
(1H, dt, J=7.4, 1.5 Hz, H-5), 6.23 (1H, t, J=7.4 Hz,
H-6), 4.59–4.54 (1H, m, H-4), 4.35 (1H, dd, J=6.6, 5.2
Hz, H-1), 2.41 (3H, s, Me), 1.80–1.70 (2H, m, H-1%/H-
4%), 1.62–1.52 (1H, m, H-1%), 1.16–1.07 (1H, m, H-4%).
13C NMR: 144.5 (Ts), 136.6 (C-5), 136.5 (Ts), 129.9
(Ts), 127.7 (Ts), 125.9 (C-6), 57.4 (C-1), 51.3 (C-4), 24.2
(C-4%), 21.7 (Me), 15.0 (C-1%). IR (KBr): 1348, 1165,
1116. MS m/z (% rel. int.): 298 (0.4), 297 (M+, 0.7), 266
(0.2), 249 (0.3), 217 (12), 201 (7), 155 (47), 91 (76), 80
(100). Anal. calcd for C13H15NO3S2: C, 52.51; H, 5.08;
N, 4.71. Found: C, 52.26; H, 4.97; N, 4.63%. The
structural assignment to (1S,2R,4R)-2b was corrobo-
rated by X-ray crystallographic analysis of the enan-
tiomer (Fig. 5).41 A racemic sample, (1R*,2S*,4S*)-2b,
recrystallized from CH2Cl2/n-heptane, melted at mp
109.5–110.5°C
3.6. Benzyl [(1S,2R)-2-hydroxycyclohex-3-enyl]-
carbamate, 11
To a solution of allylic sulfoxide 10 (55% ee; 1.32 g,
3.70 mmol) in methanol (80 ml) was added trimethyl
phosphite (525 ml, 4.44 mmol) and the mixture was
refluxed at 80°C for 5 h. The mixture was concentrated
in vacuo and the residue purified by flash chromatogra-
phy (ethyl acetate/n-pentane, 1:1) to afford the allylic
alcohol 11 as a colorless oil (0.86 g, 3.44 mmol, 93%).
[h]2D0 −55.8 (c 1.0, CH2Cl2). HPLC analysis (Chiracel
OD-H; 2-propanol/n-hexane, 1:9; 0.7 ml min−1): 58%
3.4.4.
(1R*,2R*,4S*)-3-Tosyl-2l4-thia-3-azabicyclo-
1
[2.2.2]oct-5-ene 2-oxide, (1R*,2R*,4S*)-2b. A colorless
oil, which crystallized to a white solid in the refrigera-
tor. Mp 139.0–139.5°C (CH2Cl2/heptane). HPLC analy-
sis (Chiralpak AD; 2-propanol/n-hexane, 1:4; 1.0 ml
ee; rt 13.2 (1S,2R), 22.0 (1R,2S) min. H NMR: 7.35–
7.30 (5H, m, Ph), 5.87 (1H, ABt, J=9.9, 3.5 Hz, H-4),
5.78 (1H, ABdd, J=9.9, 2.2 Hz, H-3), 5.39 (1H, d br,
J=7.3 Hz, NH
3.81–3.73 (1H, m, H-1), 2.14 (2H, s br, H-5), 2.01 (1H,
6 ), 5.09 (2H, s, Bn), 4.11 (1H, s br, H-2),
1
min−1; 230 nm): rt 27.3 (−), 36.3 (+) min. H NMR:
7.71 and 7.30 (each 2H, AA%BB%, JAB=8.4 Hz, Tos),
6.37 (1H, dd, J=8.0, 5.9 Hz, H-5), 6.11 (1H, t, J=7.5
Hz, H-6), 4.47 (1H, m, H-4), 4.00 (1H, m, H-1), 2.84–
2.79 (1H, m, H-1%), 2.43 (3H, s, Me), 2.28–2.19 (1H, m,
H-4%), 1.50–1.38 (2H, m, H-1%/H-4%). 13C NMR: 144.6
(Ts), 139.5 (C-5), 136.6 (Ts), 130.0 (Ts), 128.2 (Ts),
127.1 (C-6), 57.4 (C-1), 50.8 (C-4), 25.4 (C-4%), 21.7
(Me), 10.9 (C-1%). Anal. calcd for C13H15NO3S2: C,
52.51; H, 5.08; N, 4.71. Found: C, 52.50; H, 4.90; N,
4.62%.
s br, OH6 ), 1.80–1.72 (1H, m, H-6), 1.68–1.58 (1H, m,
H-6). 13C NMR: 156.2 (CꢀO), 136.6 (Ph), 131.6 (C-4),
128.6 (3×C, Ph), 128.2 (2×C, Ph), 127.3 (C-3), 66.8
(C-2), 65.2 (Bn), 50.7 (C-1), 24.8 (C-5), 23.5 (C-6). IR
(KBr): 3400 (m; O-H, N-H), 1700, 1500. MS: m/z (%
rel. int.) 248 (M++1, 0.5), 247 (M+, 0.3), 178 (27), 117
(30), 91 (100).
3.7. (3aS,7aR)-3a,4,5,7a-Tetrahydrobenzo[d]-
[1,3]oxazolidin-2-one, 12
3.5. Benzyl [(1S,4R)-4-(phenylsulfinyl)cyclohex-2-enyl]-
A cooled (0°C) solution of potassium tert-butoxide
(0.40 g, 3.56 mmol) in anhydrous THF (10 ml) was
added to a solution of 11 (58% ee; 0.81 g, 3.28 mmol)
in anhydrous THF (110 ml) at 0°C and the mixture was
stirred for 1 h. The reaction mixture was diluted with
aqueous NH4Cl (satd, 80 ml) at 0°C, the layers were
separated and the aqueous layer was extracted with
ether (4×20 ml). The combined organics were washed
with brine (20 ml), dried (MgSO4) and concentrated in
vacuo. Purification of the crude product by flash chro-
matography (ethyl acetate/n-pentane, 4:1) afforded the
cyclic carbamate 12 as a white solid (0.36 g, 2.58 mmol,
carbamate, 10
A solution of phenylmagnesium bromide in ether (3 M,
1.65 ml, 4.95 mmol) was added to a stirred solution of
(1R,2S,4S)-2a (50% ee; 1.22 g, 4.4 mmol) in anhydrous
THF (30 ml) at −60°C. The resultant mixture was
stirred for 30 min and then hydrolyzed with aqueous
NH4Cl (satd, 60 ml). The layers were separated and the
aqueous layer extracted with ether (3×20 ml). The
combined organics were washed with brine (20 ml),
dried (MgSO4) and concentrated in vacuo. Purification
of the crude product by flash chromatography (ethyl
acetate/n-pentane, 1:1 to 7:3) afforded the allylic sulf-
oxide 10 (1.38 g, 3.89 mmol, 88%) as a colorless oil
which crystallized to white crystals on standing in the
refrigerator. [h]2D0 +202.3 (c 1.0, CHCl3). HPLC analysis
(Chiracel OJ; 2-propanol/n-hexane, 35:65; 0.5 ml
1
79%). [h]2D0 +15.0 (c 1.0, CH2Cl2). H NMR: 6.58 (1H,
s br, NH6 ), 6.16 (1H, dt, J=10.1, 4.0 Hz, H-6), 5.81
(1H, dtt, J=10.1, 3.7, 1.8 Hz, H-7), 4.90 (1H, m, H-7a),
3.97 (1H, sex, J=3.7 Hz, H-3a), 2.28–2.18 (1H, m,
H-5), 1.99–1.89 (1H, m, H-5), 1.89–1.82 (1H, m, H-4),
1.72–1.64 (1H, m, H-4). 13C NMR: 160.3 (CꢀO), 134.3
(C-6), 122.7 (C-7), 72.5 (C-7a), 51.2 (C-3a), 25.7 (C-4),
1
min−1): 55% ee; rt 18.6 (1S,4R), 30.0 (1R,4S) min. H

2414
A. Bayer et al. / Tetrahedron: Asymmetry 13 (2002) 2407–2415
20.8 (C-5); IR (KBr): 3300, 1740, 1720. GC–MS: m/z
(% rel. int.): 139 (M+, 3), 124 (3), 111 (9), 95 (51), 67
(47), 41 (100). Anal. calcd for C7H9NO2: C, 60.42; H,
6.52; N, 10.07. Found: C, 60.66; H, 6.54; N, 9.80%.
A racemic sample of 12 melted at 83.2–84.5°C.
3.10. Benzyl N-[(1S)-cyclohex-3-enyl]carbamate, (S)-
14a
Treatment of (1R,2S,4S)-2a (52% ee; 284 mg, 1.02
mmol) according to the procedure described above
for preparation of (R)-14b afforded after flash chro-
matography (ethyl acetate/pentane, 3:7) (S)-14a as a
white solid (205 mg, 87%). Data for (S)-14a. [h]D20
3.8. (3aS,7aR)-3a,4,5,6,7,7a-Hexahydrobenzo[d]-
[1,3]oxazolidin-2-one, (3aS,7aR)-13
1
−13.9 (52% ee, c 0.895, CH2Cl2). H NMR: 7.36–7.32
(5H, m, Ph), 5.67 (1H, ABm, J=9.9 Hz, H-4), 5.59
(1H, ABm, J=9.9 Hz, H-3), 5.09 (2H, s, Bn), 4.79
(1H, s br, NH6 ), 3.87 (1H, m, H-1), 2.39 (1H, d br,
A solution of the carbamate 12 (53 mg, 0.38 mmol)
in hexane (5 ml) and ethyl acetate (3 ml) was hydro-
genated at 1 atm and 25°C for 21 h using 5% Rh–
Al2O3 (10 mg) as catalyst. The catalyst was removed
by filtration through Celite 545 and the filtrate con-
centrated in vacuo. Purification of the crude by flash
J=16.8 Hz, H-2), 2.12 (2H, s br, H-5), 1.92–1.82
(2H, m, H-2/H-6), 1.61–1.53 (1H, m, H-6). 13C NMR:
155.8 (CꢀO), 136.7 (Ph), 128.6 (2×C, Ph), 128.23
(Ph), 128.17 (2×C, Ph), 127.1 (C-4), 124.4 (C-3), 66.6
(Bn), 46.2 (C-1), 32.0 (C-2), 28.3 (C-6), 23.5 (C-5). IR
(KBr): 3300, 1680, 1540. GC–MS m/z (% rel. int.):
231 (M+, 1.1), 170 (10), 152 ( 7), 132 (6), 108 (32), 91
(100), 80 (51). Anal. calcd for C14H17NO2: C, 72.70;
H, 7.41; N, 6.06. Found: C, 72.97; H, 7.30; N, 5.97%.
A racemic sample of 14a melted at 63.0–63.5°C.
chromatography
(ethyl
acetate/n-pentane,
4:1)
afforded the cyclic carbamate (3aS,7aR)-13 as a white
solid (25 mg, 0.18 mmol, 47%). [h]2D01 +17.9 (c 1.1,
abs. EtOH) lit.16 +25.0 (c 1.0, EtOH). H NMR: 5.60
(1H, s br, NH6 ), 4.58 (1H, dt, J=4.8, 6.6 Hz, H-7a),
3.73 (1H, qua, J=6.2 Hz, H-3a), 2.03–1.96 (1H, m,
H-7), 1.86–1.70 (2H, m, H-4/H-7), 1.66–1.40 (4H, m,
H-4/H-5/2×H-6), 1.33–1.22 (1H, m, H-5). 13C NMR:
160.5 (CꢀO), 76.0 (C-7a), 51.8 (C-3a), 28.8 (C-7), 26.8
(C-4), 19.9, 19.6. GC–MS m/z (% rel. int.): 142 (4),
141 (M+, 53), 98 (100). Anal. calcd for C7H11NO2: C,
59.56; H, 7.85; N, 9.92. Found: C, 59.92; H, 7.68; N,
9.69%.
3.11. N-[(1S)-Cyclohex-3-enyl]-p-toluenesulfonamide,
(S)-14b
Trimethylsilyl iodide (412 ml, 3.03 mmol) was added
to a solution of N-benzoyloxyamine (S)-14a (52% ee;
180 mg, 0.78 mmol) in dry acetonitrile (10 ml) at
0°C. The solution was stirred at 0°C for 30 min
before methanol (2.8 ml) was added. After 10 min,
the volatiles were evaporated in vacuo and the
residue dissolved in dry CH2Cl2 (4 ml). The solution
was cooled to 0°C before triethylamine (273 ml, 1.96
mmol) and tosyl chloride (187 mg, 0.98 mmol) were
added. The reaction mixture was stirred at rt for 24
h. H2SO4 (2 M, 2 ml) was added and the aqueous
layer neutralized by saturated aqueous NaHCO3 (8
ml). The layers were separated and the aqueous layer
extracted with CH2Cl2 (3×5 ml). The combined
organics were dried (MgSO4) and concentrated in
vacuo. Purification of the crude by flash chromatog-
raphy (diethyl ether/n-pentane, 3:7) afforded the (1S)-
N-tosylamine, (S)-14b (73 mg, 0.29 mmol, 37%, 54%
ee).
3.9. N-[(1R)-Cyclohex-3-enyl]-p-toluenesulfonamide,
(R)-14b
A suspension of (1S,2R,4R)-2b (from entry 11, Table
2; 320 mg, 1.1 mmol) in aqueous NaOH (1.25 M, 5
ml) was stirred for 19 h at 25°C. The mixture was
cooled to 0°C and added aqueous HCl (0.5 M, 12
ml) and CH2Cl2 (15 ml). The layers were separated
and the aqueous layer neutralized by addition of
aqueous NaHCO3 (satd), and then extracted with
CH2Cl2 (3×15 ml). The combined organics were dried
(MgSO4) and concentrated in vacuo. Purification of
the crude by flash chromatography (ethyl acetate/n-
pentane, 1:3) afforded the (1R)-N-tosyl amine (R)-14b
as a white solid (96 mg, 0.38 mmol, 34%, 64% ee).
Mp 65.8–67.0°C. [h]2D0 +2.0 (c 1.0, CH2Cl2); HPLC
analysis (Chiralpak AD; abs. ethanol/n-hexane, 1:9;
1.0 ml min−1, 230 nm): 64% ee; rt 18.8 (1R), 21.7
Acknowledgements
1
(1S) min. H NMR: 7.76 and 7.29 (each 2H, AA%BB%,
J
AB=8.4 Hz, Ts), 5.65–5.59 (1H, m AB, 4-H), 5.50–
This work was supported by a grant from the Norwe-
gian Research Council (grant 122792/432 to A.B.)
which is gratefully acknowledged. We also thank Mr.
Jostein Johansen (University of Tromsø) and Associ-
ate Professor Helge Kjøsen (Norwegian University of
Science and Technology, Trondheim) for performing
the mass spectrometric measurements.
5.44 (1H, m AB, 3-H), 4.62 (1H, d br, J=7.7 Hz,
NH), 3.50–3.42 (1H, m, 1-H), 2.42 (3H, s, Me), 2.19
(1H, d br, J=16.9 Hz, 2-H), 2.08–2.01 (2H, m, 5-H),
1.86–1.76 (1H, m, 2-H), 1.76–1.68 (1H, m, 6-H),
1.56–1.47 (1H, m, 6-H). 13C NMR: 143.3 (C, Ar),
138.3 (C, Ar), 129.8 (2×C, Ar), 127.1 (C-4), 127.0
(2×C, Ar), 123.9 (C-3), 49.0 (C-1), 32.5 (C-2), 28.9
(C-6), 23.4 (C-5), 21.6 (Me). IR (KBr): 3270. MS m/z
(% rel. int.) 251 (M+, 1), 197 (6), 172 (21), 155 (31),
133 (65), 91 (100). Anal. calcd for C13H17NO2S: C,
62.12; H, 6.82; N, 5.57. Found: C, 62.30; H, 6.76; N,
5.46%.
References
1. Wichterle, O.; Rocek, J. Chem. Listy 1953, 47, 1768–
1780.

A. Bayer et al. / Tetrahedron: Asymmetry 13 (2002) 2407–2415
2415
2. Kresze, G.; Maschke, A.; Albrecht, R.; Bederke, K.;
Patzschke, H. P.; Smalla, H.; Trede, A. Angew. Chem.,
Int. Ed. Engl. 1962, 1, 89–98.
832; (b) Mikami, K.; Terada, M. In Lewis Acids in
Organic Synthesis; Yamamoto, H. Ed.; Wiley-VCH:
Weinheim, 2000; Vol. 2, pp. 799–847.
3. Kresze, G.; Wucherpfenning, W. Angew. Chem., Int. Ed.
25. Narasaka, K.; Iwasawa, N.; Inoue, M.; Yamada, T.;
Nakashima, M.; Sugimori, J. J. Am. Chem. Soc. 1989,
111, 5340–5345.
26. Haase, C.; Sarko, C. R.; DiMare, M. J. Org. Chem. 1995,
60, 1777–1787.
Engl. 1967, 6, 149–167.
4. Weinreb, S. M.; Staib, R. R. Tetrahedron 1982, 38,
3087–3128.
5. Bussas, R.; Kresze, H.; Mu¨nsterer, H.; Schwo¨bel, A.
Sulfur Rep. 1983, 2, 215–378.
6. Boger, D. L.; Weinreb, S. M. Hetero Diels–Alder
Methodology in Organic Synthesis; Academic Press: San
Diego, 1987; pp. 1–33.
27. Corey, E. J.; Matsumura, Y. Tetrahedron Lett. 1999, 32,
6289–6292.
28. Devine, P. N.; Oh, T. J. Org. Chem. 1992, 57, 396–399.
29. Prepared according to: Clark, R. J. H.; Coles, M. A. J.
Chem. Soc., Dalton Trans. 1974, 1462–1467.
30. Iwasawa, N.; Hayashi, Y.; Sakurai, H.; Narasaka, K.
Chem. Lett. 1989, 1581–1584.
7. Weinreb, S. M. Acc. Chem. Res. 1988, 21, 313–318.
8. Waldmann, H. Synthesis 1994, 535–551.
9. Weinreb, S. M.; Garigipati, R. S.; Gainor, J. A. Hetero-
31. Girard, C.; Kagan, H. B. Angew. Chem., Int. Ed. Engl.
cycles 1984, 21, 309–324.
1998, 37, 2922–2959.
10. (a) Anderson, G. T.; Chase, C. E.; Koh, Y.-H.; Stien, D.;
Weinreb, S. M. J. Org. Chem. 1998, 63, 7594–7595; (b)
Stien, D.; Anderson, G. T.; Chase, C. E.; Koh, Y.-H.;
Weinreb, S. M. J. Am. Chem. Soc. 1999, 121, 9574–9579.
11. (a) Heintzelman, G. R.; Weinreb, S. M.; Parvez, M. J.
Org. Chem. 1996, 61, 4594–4599; (b) Heintzelman, G. R.;
Fang, W.-K.; Keen, S. P.; Wallace, G. A.; Weinreb, S.
M. J. Am. Chem. Soc. 2001, 123, 8851–8853.
12. Remiszewski, S. W.; Whittle, R. R.; Weinreb, S. M. J.
Org. Chem. 1984, 49, 3243–3244.
13. (a) Garigipati, R. S.; Freyer, A. J.; Whittle, R. R.;
Weinreb, S. M. J. Am. Chem. Soc. 1984, 106, 7861–7867;
(b) Garigipati, R. S.; Weinreb, S. M. J. Am. Chem. Soc.
1983, 105, 4499–4501.
14. Anwar, B.; Grimsey, P.; Hemming, K.; Krajniewski, M.;
Loukou, C. Tetrahedron Lett. 2000, 41, 10107–10110.
15. Whitesell, J. K.; James, D.; Carpenter, J. F. J. Chem.
Soc., Chem. Commun. 1985, 1449–1450.
32. Beck, A. K.; Bastani, B.; Plattner, D. A.; Petter, W.;
Seebach, D.; Braunschweigen, H.; Gyri, P.; La Vecchia,
L. Chimia 1991, 45, 238–244.
33. Altava, B.; Burguete, M. I.; Fraile, J. M.; Garc´ıa, J. I.;
Luis, S. V.; Mayoral, J. A.; Royo, A. J.; Vicent, M. J.
Tetrahedron: Asymmetry 1997, 8, 2561–2570.
34. Ito, Y. N.; Ariza, X.; Beck, A. K.; Boha´c, A.; Ganter, C.;
Gawley, R. E.; Ku¨hnle, F. N. M.; Tuleja, J.; Wang, Y.
M.; Seebach, D. Helv. Chim. Acta 1994, 77, 2071–2110.
35. Almquist, F.; Torstensson, L.; Gudmundsson, A.; Frejd,
T. Angew. Chem., Int. Ed. Engl. 1997, 36, 376–377.
36. Periasamy, M.; Venkatraman, L.; Sivakumar, S.; Sam-
pathkumar, N.; Ramanathan, C. R. J. Org. Chem. 1999,
64, 7643–7645.
37. Wang, Z.-M.; Sharpless, K. B. J. Org. Chem. 1994, 59,
8302–8303.
38. Larrow, J. F.; Jacobsen, E. N.; Gao, Y.; Hong, Y.; Nie,
X.; Zepp, C. M. J. Org. Chem. 1994, 59, 1939–1942.
39. Gothelf, K. V.; Jørgensen, K. A. J. Org. Chem. 1995, 60,
6847–6851.
16. Remiszewski, S. W.; Yang, J.; Weinreb, S. M. Tetra-
hedron Lett. 1986, 27, 1853–1856.
17. Hamada, T.; Sato, H.; Hikota, M.; Yonemitsu, O. Tetra-
hedron Lett. 1989, 30, 6405–6408.
40. Zhang, Y.; Flann, C. J. J. Org. Chem. 1998, 63, 1372–
1378.
18. Narasaka, K. Synthesis 1991, 1–11.
41. Inquiries concerning the X-ray structures of endo-2a and
(1R,2S,4S)-2b should be addressed to L.K.H. Crystallo-
graphic data (excluding structure factors) for structures
endo-2a and (1R,2S,4S)-2b have been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary publication nos. CCDC 181233 and CCDC 178740,
respectively. Copies of the data can be obtained free of
charge, on application to CCDC, 12 Union Road, Cam-
bridge CB2 1EZ, UK (Fax: +44-(0)1223-336033 or e-
mail: deposit@ccdc.cam.ac.uk).
19. Kagan, H. B.; Riant, O. Chem. Rev. 1992, 92, 1007–1019.
20. Dias, L. C. J. Braz. Chem. Soc. 1997, 8, 289–332.
21. Bayer, A.; Gautun, O. R. Tetrahedron Lett. 2000, 41,
3743–3746.
22. Bayer, A.; Gautun, O. R. Tetrahedron: Asymmetry 2001,
12, 2937–2939.
23. Seebach, D.; Beck, A. K.; Heckel, A. Angew. Chem., Int.
Ed. Engl. 2001, 40, 92–138.
24. Selected reviews about chiral Ti(IV)-catalysts: (a)
Duthaler, R. O.; Hafner, A. Chem. Rev. 1992, 92, 807–