Regio- and stereoselective 1,3-oxathiolane formation in the reaction of thiolactones with optically active oxiranes

Article abstract of DOI:10.1002/hlca.200490205

The reactions of 3H-isobenzofuran-1-thione (1) with (S)-2-methyloxirane (2) and (R)-2-phenyloxirane (6) in the presence of SiO₂ in anhydrous CH₂Cl₂ led to two pairs of diastereoisomeric spirocyclic 1,3-oxathiolanes, i.e., 3 and 4 with a Me group at C(5′), and 7 and 8 with a Ph group at C(4′), respectively (Schemes 2 and 3). In both cases, 3H-isobenzofuran-1-one (5) was formed as a main product. The analogous reactions of 3,4-dihydro-2H-[1]benzopyran-2-thione (9) and 3,4,5,6-tetrahydro-2H-pyran-2- thione (14) with 2 and 6 yielded four pairs of the corresponding diastereoisomeric spirocyclic compounds 10 and 11, 12 and 13, 15 and 16, and 18 and 19, respectively (Schemes 4-7). In the reaction of 14 with 6, the 1,3-oxathiolane 20 with a Ph group at C(2) was also formed. The structures of 3, 7, 8, 10, 19, and 20 were established by X-ray crystallography (Figs. 1-4). In contrast to the thiolactones 1, 9, and 14, the thioesters 21a-21d did not react with (R)-2-phenyloxirane (6) either in the presence of SiO₂ or under more-drastic conditions with BF₃ · Et₂O or SnCl₄ (Scheme 8). The results show that spirocyclic 1,3-oxathiolanes can be prepared from thiolactones with oxiranes. The nucleophilic attack of the thiocarbonyl S-atom at the SiO₂-activated oxirane ring proceeds with high regio- and stereoselectivity via an S_N2-type mechanism.

Full text of DOI:10.1002/hlca.200490205

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Helvetica Chimica Acta Vol. 87 (2004)
Regio- and Stereoselective 1,3-Oxathiolane Formation in the Reaction of
Thiolactones with Optically Active Oxiranes
by Changchun Fu1), Anthony Linden, and Heinz Heimgartner*
Organisch-chemisches Institut der Universit‰t Z¸rich, Winterthurerstrasse 190, CH-8057 Z¸rich
The reactions of 3H-isobenzofuran-1-thione (1) with (S)-2-methyloxirane (2) and (R)-2-phenyloxirane (6)
in the presence of SiO2 in anhydrous CH2Cl2 led to two pairs of diastereoisomeric spirocyclic 1,3-oxathiolanes,
i.e., 3 and 4 with a Me group at C(5'), and 7 and 8 with a Ph group at C(4'), respectively (Schemes 2 and 3). In
both cases, 3H-isobenzofuran-1-one (5) was formed as a main product. The analogous reactions of 3,4-dihydro-
2H-[1]benzopyran-2-thione (9) and 3,4,5,6-tetrahydro-2H-pyran-2-thione (14) with 2 and 6 yielded four pairs of
the corresponding diastereoisomeric spirocyclic compounds 10 and 11, 12 and 13, 15 and 16, and 18 and 19,
respectively (Schemes 4 7). In the reaction of 14 with 6, the 1,3-oxathiolane 20 with a Ph group at C(2) was also
formed. The structures of 3, 7, 8, 10, 19, and 20 were established by X-ray crystallography (Figs. 1 4). In
contrast to the thiolactones 1, 9, and 14, the thioesters 21a 21d did not react with (R)-2-phenyloxirane (6)
either in the presence of SiO2 or under more-drastic conditions with BF3 ¥ Et2O or SnCl4 (Scheme 8). The results
show that spirocyclic 1,3-oxathiolanes can be prepared from thiolactones with oxiranes. The nucleophilic attack
of the thiocarbonyl S-atom at the SiO2-activated oxirane ring proceeds with high regio- and stereoselectivity via
an SN2-type mechanism.
1. Introduction. The formation of 1,3-oxathiolanes via the Lewis acid catalyzed
reaction of thioketones with oxiranes has been investigated thoroughly in recent years
[1 6]. The results reported for this novel synthetic approach indicate that the reactions
proceed with high regio- and stereoselectivity via an SN2-type mechanism (Scheme 1).
In the case of 2-alkyl-substituted oxiranes, the nucleophilic thiocarbonyl S-atom
attacks preferentially at C(3) to give the 5-substituted 1,3-oxathiolanes with retention
of configuration at C(2) of the oxirane. On the other hand, 2-phenyloxirane is attacked
mainly at C(2) under inversion of configuration to yield the 4-Ph-substituted products.
Similar reactions have been observed with 1,3-thiazole-5(4H)-thiones [7][8], with
cyclic trithiocarbonates [9], and with a rhodanine derivative [10].
Scheme 1
1
)
Part IV of the projected Ph.D. thesis of C.F., University of Zurich. Part I: [1], Part II: [2], Part III: [3].
¹ 2004 Verlag Helvetica Chimica Acta AG, Z¸rich

Helvetica Chimica Acta Vol. 87 (2004)
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So far, the reaction of thioesters with oxiranes to afford 1,3-oxathiolanes, i.e.,
monothioorthoesters, has not been reported. With the aim of further extending the
scope of the formation of 1,3-oxathiolanes, reactions of thiolactones such as 3H-
isobenzofuran-1-thione (1), 3,4-dihydro-2H-[1]benzopyran-2-thione (9), 3,4,5,6-tetra-
hydro-2H-pyran-2-thione (14), as well as of thioesters, i.e., O-ethyl 2,2-dimethyl-
thiopropanoate (21a), O-methyl thiooctanoate (21b), O-methyl thiobenzoate (21c),
and O-phenyl thiobenzoate (21d), with optically active oxiranes were carried out. In
the present paper, the results of the reactions of 1, 9, and 14 with (S)-2-methyloxirane
(2) and (R)-2-phenyloxirane (6), and those of 21a 21d with 6 are described.
2. Results. 2.1. Reaction of 3H-Isobenzofuran-1-thione (1) with (S)-2-Methylox-
irane (2). The reaction of 1 with 2 in a molar ratio of 1:2 was carried out in anhydrous
CH2Cl2 at room temperature under N2 atmosphere in the presence of SiO2. After
stirring for 10 h, filtration and the usual workup by means of column chromatography
(CC) and HPLC on a chiral solid phase gave two diastereoisomeric spirocyclic 1,3-
oxathiolanes 3 and 4 in 16 and 8% yield, respectively. The reaction was repeated under
the same conditions, and the analysis of the reaction mixture by 1H-NMR spectroscopy
showed 26% of 3, 10% of 4, as well as 54% of 3H-isobenzofuran-1-one (5) and 9% of
1, referenced to a weighed amount of 1,1,2,2-tetrachloroethane as a standard
(Scheme 2). The enantiomeric excess (ee) of the products (> 99%) was determined
by analytical HPLC (Chiralcel OD-H, hexane/i-PrOH 25 :1).
Scheme 2
The structures of 3 and 4 were assigned on the basis of the elemental analyses, IR,
1H- and 13C-NMR (2D-NOESY, HSQC, HSQC-TOCSY, and HMBC), and mass
spectra, which clearly indicated the relative configurations of the products. The 2D-
NOESY spectrum of 3 showed one cross-signal between HÀC(7) at 7.51 7.50 ppm
and Me at 1.48ppm, and that of 4 gave one cross-signal between HÀC(7) at 7.49
7.48ppm and H ÀC(5') at 4.70 4.67 ppm. The formation of 3 and 4 proceeded by
nucleophilic attack of the thiocarbonyl S-atom at C(3) and, for this reason, the
configuration at C(2) of the oxirane 2 is retained. Therefore, the configuration at C(1)
in 3 and 4 should be (R) and (S), respectively, relative to the known (5'S)-
configuration2). Finally, the structure of 3 was established by X-ray crystallography
(Fig. 1).
2
)
This proposal was proven by the X-ray crystal-structure analysis of 10 (see Sect. 2.3).

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Helvetica Chimica Acta Vol. 87 (2004)
Fig. 1. ORTEP Plot [11] of the molecular structure of 3 (arbitrary numbering of the atoms; displacement
ellipsoids with 50% probability)
The crystals of 3 were enantiomerically pure, but, due to the quality of the crystals,
the absolute configuration of the molecule could not be confirmed unequivocally by
refinement of the absolute structure parameter. The enantiomer used in the refinement
was, therefore, chosen to correspond with the known (5'S)-configuration. Based on this
assumption, the stereogenic center C(1) has the (R)-configuration.
2.2. Reaction of 3H-Isobenzofuran-1-thione (1) with (R)-2-Phenyloxirane (6). The
analogous reaction of 1 with 6 (molar ratio 1:1.5) in anhydrous CH2Cl2 at room
temperature for 10 h under N2 atmosphere in the presence of SiO2 gave two
diastereoisomeric spiroheterocycles 7 and 8 in 29 and 10% yield, respectively.
Repetition of the reaction led to 7, 8, 5, and 1 in 29, 16, 29, and 26% yield, respectively,
based on the 1H-NMR spectrum of the reaction mixture and 1,1,2,2-tetrachloroethane
as an internal standard (Scheme 3). The ee values of the products (> 99%) were
determined by analytical HPLC (Chiralcel OD-H, hexane/i-PrOH 25 :1). It was to be
expected that 7 and 8 were formed via nucleophilic attack of the S-atom at C(2) of 6
with inversion of configuration, leading to the (S)-configuration at C(4') of the
products.
Scheme 3

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The structures of 7 and 8 were assigned on the basis of their elemental analyses and
spectroscopic data, particularly 2D-NOESY, HSQC, HSQC-TOCSY, and HMBC
NMR spectra, and they were confirmed by X-ray crystallography (Fig. 2). The 2D-
NOESY spectrum of 7 showed no significant cross-signals that could be used for the
determination of the relative configuration, but that of 8 gave one weak cross-signal
between two ortho-H atoms of Ph at 7.59 7.58ppm and two H ÀC(3) at 5.23
5.17 ppm, which indicated that 8 has the cis-configuration, i.e., the (1R,4'S)-
configuration. Therefore, the diastereoisomer 7 should have the (1S,4'S)-configuration,
in accordance with the X-ray crystal-structure analysis.
Fig. 2. ORTEP Plots [11] of the molecular structures of a) 7 and b) 8 (arbitrary numbering of the atoms;
displacement ellipsoids with 50% probability)
The crystals of 7 and 8 were enantiomerically pure, and the absolute configurations
of the molecules have been determined independently by the diffraction experiment
and found to be (1S,4'S) and (1R,4'S), respectively.
2.3. Reaction of 3,4-Dihydro-2H-[1]benzopyran-2-thione (9) with (S)-2-Methylox-
irane (2). The reaction of 9 with 2 in a molar ratio of 1:2 was carried out in anhydrous
CH2Cl2 at room temperature under N2 atmosphere in the presence of SiO2. After
stirring for 3 d, filtration and the usual workup by means of column chromatography
(CC) gave a 4 :1 mixture (1H-NMR) of two diastereoisomeric spirocyclic 1,3-
oxathiolanes 10 and 11 in 40% total yield (Scheme 4). Separation of the mixture by
HPLC led to 10 in 29% yield, but 11 could not be obtained in pure form because of its
partial epimerization to 10. The ee of 10 (> 99%) was determined by analytical HPLC
(Chiralcel OD-H, hexane/i-PrOH 50 :1).

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Scheme 4
The structure of 10 was again assigned on the basis of elemental analysis and
spectroscopic data, particularly those obtained from NMR experiments. The 2D-
NOESY spectrum of 10 showed one cross-signal between HÀC(8) at 6.83 ppm and
HÀC(5') at 4.83 4.78 ppm, which clearly indicated the (S)-configuration at C(2)
relative to the known (5'S)-configuration. Therefore, the diastereoisomer 11 should
have the (2R,5'S)-configuration. Finally, the structure of 10 was established by X-ray
crystallography (Fig. 3).
Fig. 3. ORTEP Plot [11] of the molecular structure 10 (arbitrary numbering of the atoms; displacement
ellipsoids with 50% probability)
The crystals of 10 were enantiomerically pure and the absolute configuration of the
molecule has been determined independently by the diffraction experiment: the
molecule has the expected (2S,5'S)-configuration.
2.4. Reaction of 9 with (R)-2-Phenyloxirane (6). The analogous reaction of 9 with 6
(molar ratio 1:1.5) in anhydrous CH2Cl2 at room temperature for 3 d under N2
atmosphere in the presence of SiO2 gave two diastereoisomeric spirocyclic compounds
12 and 13 in 35 and 7% yield, respectively. The ee values of the products, determined by
analytical HPLC (Chiralcel OD-H, hexane/i-PrOH 50 :1), showed that 12 and 13 were
formed with lower stereoselectivity, and partial racemization of ca. 10% was observed
(Scheme 5).

Helvetica Chimica Acta Vol. 87 (2004)
2301
Scheme 5
The structures of 12 and 13 were assigned in the same way as that of 10. According
to previous reactions of thiocarbonyl compounds with 6, the formation of 12 and 13 was
expected to take place mainly via inversion of the configuration at C(2) of 6, which
leads to the (4'S)-configuration of the products. The 2D-NOESY spectrum of 12
showed two cross-signals between two ortho-H atoms of Ph at 7.40 7.39 ppm and two
HÀC(3) at 2.60 2.55 and 2.51 2.46 ppm, respectively, which indicated the (2R,4'S)-
configuration. On the other hand, the 2D-NOESY spectrum of 13 showed one cross-
signal between two ortho-H atoms of Ph at 7.53 ppm and HÀC(8) at 6.95 6.93 ppm,
and another one between HÀC(4') at 4.94 ppm and two HÀC(3) at 2.51 2.40 ppm,
indicating the (2S,4'S)-configuration.
2.5. Reaction of 3,4,5,6-Tetrahydro-2H-pyran-2-thione (14) with (S)-2-Methyloxi-
rane (2). The reaction of 14 with 2 (molar ratio 1:2) in anhydrous CH2Cl2 at 08 for 2 d
under N2 atmosphere in the presence of SiO2 gave two diastereoisomeric spirocyclic
1,3-oxathiolanes 15, 16, together with lactone 17 in 63, 22, and 15% yield, respectively,
based on the 1H-NMR spectrum of the reaction mixture and 1,1,2,2-tetrachloroethane
as a standard (Scheme 6). Separation of the two diastereoisomers by MPLC and HPLC
gave 15 as a pure compound in 38% yield, but 16 was obtained only in 90% purity
because of its partial epimerization to 15. The ee value of 15 was determined by
analytical HPLC as > 99% (Chiralcel OB, hexane/EtOH 80 :1).
Scheme 6
As in the previous cases, the structures of 15 and 16 were assigned on the basis of
their elemental analysis and spectroscopic data. The 2D-NOESY spectrum of 15
showed one cross-signal between HÀC(2) at 4.65 4.59 ppm and one HÀC(7) at 3.94
3.90 ppm, which indicated the trans-configuration, i.e., the (R)-configuration at C(5)
relative to the known (2S)-configuration. On the other hand, the spectrum of 16
showed one cross-signal between HÀC(2) at 4.33 4.28ppm and two H ÀC(10) at
2.11 2.01 ppm, which implies the (2S,5S)-configuration.

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Helvetica Chimica Acta Vol. 87 (2004)
2.6. Reaction of 14 with (R)-2-Phenyloxirane (6). The analogous reaction of 14 with
6 (molar ratio 1:1.5) in anhydrous CH2Cl2 at room temperature for 11 h under N2
atmosphere in the presence of SiO2 gave three spirocyclic 1,3-oxathiolanes 18, 19, and
20 in 54, 11, and 8% yield, respectively. The ee values of the products, determined by
analytical HPLC (Chiralcel OB, hexane/EtOH 80 :1), showed that the reaction
proceeded with lower stereoselectivity and partial racemization (10% in the case of 19;
Scheme 7).
Scheme 7
The structures of 18, 19, and 20 were assigned as usual. The 2D-NOESY spectrum
of 18 showed one cross-signal between two ortho-H atoms at 7.38 7.36 ppm and two
HÀC(10) at 2.27 2.16 ppm, indicating the trans-(3S,5S)-configuration. The 1D-
NOESY spectrum of 19, on irradiation of HÀC(3) at 4.8ppm, gave one NOE signal
for two HÀC(10) at 2.17 2.05 ppm, corresponding to the cis-(3S,5R)-configuration.
Finally, the 2D-NOESY spectrum of 20 showed one cross-signal between two ortho-H
atoms of Ph at 7.47 7.45 ppm and one HÀC(7) at 4.06 4.02 ppm, and another one
between HÀC(2) at 5.30 ppm and two HÀC(10) at 2.17 2.08ppm, indicating the
(2R,5R)-configuration. The structures and absolute configurations of 19 and 20 were
established by X-ray crystallography (Fig. 4).
Fig. 4. ORTEP Plots [11] of the molecular structures of a) 19 and b) 20 (displacement ellipsoids with 50%
probability)
The crystals of 19 and 20 were enantiomerically pure, and the absolute
configurations of the molecules have been determined independently by the diffraction
experiment. The molecules of 19 and 20 have the (3S,5R)- and (2R,5R)-configuration,
respectively.

Helvetica Chimica Acta Vol. 87 (2004)
2303
2.7. Reactions of Thioesters 21a 21d with (R)-2-Phenyloxirane (6). In analogy to
the reactions with thiolactones (Sect. 2.1 2.6), the reactions of 21a 21d with 6 were
carried out in anhydrous CH2Cl2 at room temperature for 2 6 d under an N2
atmosphere in the presence of SiO2. Surprisingly, none of the expected 1,3-oxathiolanes
was formed. Therefore, the reactions of 21a 21b with 6 were repeated in anhydrous
CH2Cl2 at À 788 for 20 30 min under an N2 atmosphere in the presence of the stronger
Lewis acids BF3 ¥ Et2O or SnCl4, but they did not lead to any of the expected product
(Scheme 8).
Scheme 8
3. Discussion and Conclusions. The results presented show that thiolactones 1, 9,
and 14 react with the monosubstituted oxiranes 2 and 6 to yield the spirocyclic 1,3-
oxathiolanes with high regio- and stereoselectivity. On the other hand, no reactions
occur between the thioesters 21a 21d and 6. An SN2-type mechanism for the 1,3-
oxathiolane formation is proposed in Scheme 9, whereby the nucleophilic thiocarbonyl
S-atom favorably attacks the C(3)-atom (OÀC(3) cleavage) of the activated (S)-2-
methyloxirane (2) to give the thiocarbonylium ion A with retention of the
configuration. The latter undergoes ring closure by nucleophilic addition of the O-
atom from the si- and re-face of the thiocarbonylium group to yield the spirocyclic 1,3-
oxathiolanes 15 and 16, respectively. On the other hand, the addition to (R)-2-
phenyloxirane (6) occurs selectively at the C(2)-atom (OÀC(2) cleavage) with
inversion of the configuration leading to intermediate B. Cyclization of B by addition of
the O-atom from the re- and si-face gives 18 and 19, respectively. The partial loss of the
stereochemical integrity of the phenyloxirane moiety in the formation of 19 may be
interpreted by a competing reaction in which the oxirane ring-opening takes place prior
to the nucleophilic attack (SN1-type). The formation of lactones in the cases of 1 and 14
can be explained by the hydrolysis of intermediates of type A and B.
Although thiolactones 9 and 14 are enolizable, their reactions with oxiranes 2 and 6
do not yield the open-chain enesulfanyl alcohols apart from the spirocyclic 1,3-
oxathiolanes, in contrast to the reactions of thiocamphor with oxiranes [2].
The observed epimerizations of 11 and 16 to the thermodynamically more-stable
epimers 10 and 15, respectively, proceed smoothly during column chromatography on
SiO2. This isomerization can be explained via acid-catalyzed ring opening of 1,3-
oxathiolanes, as has been described in Scheme 9 of [2].

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 9
We thank the analytical services of our institute for NMR and mass spectra, and elemental analyses, Mr. B.
B¸rgi for his assistance with the determination of the crystal structures, and the Swiss National Science
Foundation and F. Hoffmann-La Roche AG, Basel, for financial support.
Experimental Part
1. General. See [12]. The thiolactones 1 [13], 9 [14], and 14 [15] have been prepared by thionation of the
corresponding lactones according to the literature procedures. Similarly, the thioesters 21a 21d were obtained
from the esters by treatment with Lawesson×s reagent [16]. Optical rotations: Perkin-Elmer-241 polarimeter
(c ˆ 1, in THF). IR Spectra: film or KBr, cmÀ1. NMR Spectra: at 600 (1H) and 150.9 MHz (13C) in CDCl3.
Enantiomeric excesses (ee) were determined by anal. HPLC on a Chiralcel OD-H or Chiralcel OB column.
2. General Procedure for the Reactions of 3H-Isobenzofuran-1-thione (1), 3,4-Dihydro-2H-[1]benzopyran-
2-thione (9), and 3,4,5,6-Tetrahydro-2H-pyran-2-thione (14) with (S)-Methyl- and (R)-Phenyloxirane (2 and 6,
resp.). To the soln. of 1, 9, or 14 (ca. 1 mmol), and oxirane 2 or 6 (ca. 2 mmol) in anh. CH2Cl2 (15 ml) under N2
atmosphere, 4.5 g of silica gel (SiO2, Uetikon-Chemie Chromatographiegel C-560) were added at r.t. or 08. After
stirring the suspension for 10 h 3 d at r.t. or 08, the mixture was filtered, and the residue was washed with Et2O
(4Â). Then, the combined filtrate was evaporated in vacuo. and the products were separated by
chromatography (SiO2 or Alox; hexane/Et2O, or hexane/AcOEt; CC, MPLC or HPLC).
3. Reactions of 1. 3.1. With (S)-2-Methyloxirane (2). Reaction of 1 (300 mg, 2 mmol) with 2 (232 mg,
4 mmol) and 4.5 g of SiO2 at r.t., 34 h, and CC (Alox, hexane/Et2O 10 :1) yielded 115 mg (28%) of a mixture of
(1R,5'S)- and (1S,5'S)-1,3-dihydro-5'-methylspiro[isobenzofuran-1,2'-[1,3]oxathiolane] (3 and 4, resp.). Sepa-
ration of the two diastereoisomers by HPLC (Chiralcel OD column, hexane/i-PrOH 25 :1) gave 68mg (16%) of
3 and 35 mg (8%) of 4. Repetition of the reaction of 1 (150 mg, 1 mmol) with 2 (116 mg, 2 mmol) for 10 h
yielded 26% of 3, 10% of 4, and 54% of 3H-isobenzofuran-1-one (5) based on 1H-NMR analysis of the reaction
mixture and a weighed amount of 1,1,2,2-tetrachloroethane as a standard. In addition, 9% of 1 remained
(Scheme 2).
23
D
Data of 3: Colorless crystals. M.p. 64.4 65.18. ‰aŠ ˆ ‡136.4 (> 99% ee). IR (KBr): 3081w, 3049w, 3022w,
2975m, 2936m, 2915m, 2904m, 2864m, 1643w, 1476w, 1461m, 1450w, 1385w, 1358w, 1349m, 1281m, 1253s, 1227w,
1193w, 1182w, 1170w, 1140m, 1110m, 1088m, 1037s, 1009s, 998s, 962m, 951s, 937s, 912m, 8 52m, 768s, 732w, 713w.
1H-NMR: 7.51 7.50 (m, HÀC(7)); 7.38 7.36 ( m, HÀC(5), HÀC(6)); 7.23 7.21 (m, HÀC(4)); 5.15 (d, J ˆ 12.6,
1 HÀC(3)); 5.09 (d, J ˆ 12.6, 1 HÀC(3)); 4.67 4.64 (m, HÀC(5')); 3.36 (dd, J ˆ 10.0, 4.7, 1 HÀC(4')); 3.03 (t,
J ˆ 10.1, 1 HÀC(4')); 1.48( d, J ˆ 6.1, Me). 13C-NMR: 139.4 (s, C(3a)); 138.1 (s, C(7a)); 128.8 (d, C(5)); 128.3 (d,
C(6)); 124.1 (d, C(7)); 124.0 (s, C(1)); 121.0 (d, C(4)); 78.9 (d, C(5')); 72.0 (t, C(3)); 41.6 (t, C(4')); 19.1 (q, Me).

Helvetica Chimica Acta Vol. 87 (2004)
2305
‡
‡
ESI-MS (MeOH ‡ NaI): 439 (5, [2 M ‡ Na] ), 231 (100, [M ‡ Na] ), 157 (45). Anal. calc. for C11H12O2S
(208.28): C 63.43, H 5.81, S 15.40; found: C 63.35, H 5.86, S 15.40.
Crystals of 3 suitable for the X-ray crystal-structure determination were grown from hexane/i-PrOH.
23
D
Data of 4: Colorless oil. ‰aŠ ˆ À63.7 (> 99% ee). IR (film): 3078w, 3039w, 2976m, 2930m, 2868m, 1612w,
1463m, 1437w, 1378m, 1353m, 1307w, 1281m, 1251s, 1198w, 1176w, 1140w, 1113s, 1088m, 1036s, 1025s, 1012s, 955s,
1
941s, 924s, 757s, 720m, 711w. H-NMR: 7.49 7.48( m, HÀC(7)); 7.37 7.35 (m, HÀC(5), HÀC(6)); 7.23 7.21
(m, HÀC(4)); 5.20 (d, J ˆ 12.6, 1 HÀC(3)); 5.05 (d, J ˆ 12.6, 1 HÀC(3)); 4.70 4.67 (m, HÀC(5')); 3.35 (dd,
J ˆ 10.6, 5.2, 1 HÀC(4')); 3.17 (dd, J ˆ 10.6, 8.0, 1 HÀC(4')); 1.53 (d, J ˆ 6.2, Me). 13C-NMR: 139.2 (s, C(7a));
138.7 (s, C(3a)); 129.5 (d, C(5)); 128.1 (d, C(6)); 125.2 (s, C(1)); 123.4 (d, C(7)); 120.9 (d, C(4)); 81.2 (d, C(5'));
‡
71.6 (t, C(3)); 40.3 (t, C(4')); 20.3 (q, Me). ESI-MS (MeOH ‡ NaI): 439 (5, [2 M ‡ Na] ), 231 (100, [M ‡
‡
Na] ), 157 (17). Anal. calc. for C11H12O2S (208.28): C 63.43, H 5.81, S 15.40; found: C 63.43, H 5.89, S 15.46.
3.2. With (R)-2-Phenyloxirane (6). Reaction of 1 (150 mg, 1 mmol) with 6 (180 mg, 1.5 mmol) and 4.5 g of
SiO2 at r.t., 10 h, and CC (Alox, hexane/Et2O 10 :1) yielded 79 mg (29%) of (1S,4'S)- and 26 mg (10%) of
(1R,4'S)-1,3-dihydro-4'-phenylspiro[isobenzofuran-1,2'-[1,3]oxathiolane] (7 and 8, resp.). Repetition of the
reaction of 1 (150 mg, 1 mmol) with 6 (180 mg, 1.5 mmol) for 10 h yielded 29% of 7, 16% of 8, and 29% of 5
based on 1H-NMR analysis of the reaction mixture and a weighed amount of 1,1,2,2-tetrachloroethane. In
addition, 26% of 1 remained (Scheme 3).
23
D
Data of 7: Colorless crystals. M.p. 112.5 113.48. ‰aŠ ˆ À63.9 (> 99% ee). IR (KBr): 3050w, 3028w, 2981w,
2942m, 2886w, 2874m, 1601w, 1495m, 1475w, 1462s, 1351m, 1303w, 1283s, 1251s, 1236s, 1197m, 1147m, 1108s,
1085m, 1054vs, 1018vs, 1007vs, 98 4s, 962vs, 947vs, 938vs, 929vs, 8 74w, 795w, 766vs, 752s, 702s. 1H-NMR: 7.57 (d,
J ˆ 6.9, HÀC(7)); 7.53 (d, J ˆ 7.4, 2 arom. H of Ph); 7.41 7.36 (m, HÀC(5), 2 arom. H of Ph, HÀC(6)); 7.31
7.28( m, 1 arom. H of Ph); 7.26 7.24 (m, HÀC(4)); 5.19 (d, J ˆ 12.6, 1 HÀC(3)); 5.13 (d, J ˆ 12.6, 1 HÀC(3));
4.95 (dd, J ˆ 5.9, 2.2, HÀC(4')); 4.68( dd, J ˆ 9.4, 5.9, 1 HÀC(5')); 4.51 (dd, J ˆ 9.3, 2.3, 1 HÀC(5')). 13C-NMR:
142.5 (s, 1 arom. C of Ph); 139.6 (s, C(7a)); 137.5 (s, C(3a)); 130.0 (d, C(5)); 129.0 (d, 2 arom. CH of Ph); 128.4
(d, C(6)); 127.8( d, 1 arom. CH of Ph); 127.4 (d, 2 arom. CH of Ph); 125.8( s, C(1)); 124.2 (d, C(7)); 121.1 (d,
‡
C(4)); 77.0 (t, C(5')); 72.2 (t, C(3)); 54.2 (d, C(4')). CI-MS (NH3): 271 (1, [M ‡ H] ), 153 (9), 152 (100). Anal.
calc. for C16H14O2S (270.35): C 71.08, H 5.22, S 11.86; found: C 70.92, H 5.03, S 11.63.
Crystals of 7 suitable for the X-ray crystal-structure determination were grown from Et2O/hexane.
23
D
Data of 8: Colorless crystals. M.p. 120.4 124.08. ‰aŠ ˆ ‡61.2 (> 99% ee). IR (KBr): 3079w, 3061w, 3029w,
2978w, 2940w, 2923w, 2879w, 1600w, 1492w, 1461m, 1454w, 1367w, 1354w, 1281w, 1257m, 1242m, 1200w, 1189w,
1110m, 1082w, 1061s, 1047m, 1009s, 992s, 973m, 949s, 927m, 8 59w, 755s, 726w, 698s. 1H-NMR: 7.59 7.58( m,
HÀC(7), 2 arom. H of Ph); 7.42 7.39 (m, HÀC(5), HÀC(6)); 7.37 7.35 (m, 2 arom. H of Ph); 7.31 7.28( m, 1
arom. H of Ph); 7.27 7.24 (m, HÀC(4)); 5.21 (d, J ˆ 12.6, 1 HÀC(3)); 5.19 (d, J ˆ 12.6, 1 HÀC(3)); 5.08( dd,
J ˆ 10.4, 6.4, HÀC(4')); 4.56 (dd, J ˆ 9.3, 6.4, 1 HÀC(5')); 4.26 (dd, J ˆ 10.3, 9.5, 1 HÀC(5')). 13C-NMR: 139.5 (s,
C(7a)); 137.8( s, C(3a)); 137.1 (s, 1 arom. C of Ph); 130.0 (d, C(5)); 129.0 (d, 2 arom. CH of Ph); 128.6 (d, 2 arom.
CH of Ph); 128.4 (d, C(6)); 128.2 (d, 1 arom. CH of Ph); 126.0 (s, C(1)); 124.2 (d, C(4)); 121.0 (d, C(7)); 77.0 (t,
‡
C(5')); 72.4 (t, C(3)); 56.6 (d, C(4')). CI-MS (NH3): 271 (1, [M ‡ H] ), 153 (9), 152 (100). Anal. calc. for
C16H14O2S (270.35): C 71.08, H 5.22, S 11.86; found: C 71.00, H 5.02, S 11.78.
Crystals of 8 suitable for the X-ray crystal-structure determination were grown from Et2O/hexane.
4. Reactions of 9. 4.1. With (S)-2-Methyloxirane (2). Reaction of 9 (328mg, 2 mmol) with 2 (232 mg,
4 mmol) and 4.5 g of SiO2 at r.t., 3 d; CC (SiO2, hexane/AcOEt 10 :1) yielded 180 mg (40%) of a mixture of
(2S,5'S)- and (2R,5'S)-3,4-dihydro-5'-methylspiro[1-benzopyran-2(2H),2'-[1,3]oxathiolane] (10 and 11, resp.).
The 1H-NMR spectrum of the mixture showed 32% of 10 and 8% of 11. Separation of the two diastereoisomers
by HPLC (Nucleosil 100-7 column, hexane/THF 125 :1) gave 130 mg (29%) of 10, but 11 could not be purified
due to its partial epimerization to 10 (Scheme 4).
23
D
Data of 10: Colorless crystals. M.p. 69.0 70.18. ‰aŠ ˆ ‡217.4 (> 99% ee). IR (KBr): 3075w, 3053w, 3038w,
2989w, 2979w, 2966m, 2921m, 2851w, 1607w, 1580m, 1487s, 1457m, 1445m, 1379w, 1352w, 1345w, 1324w, 1299w,
1275w, 1234s, 1201s, 1174w, 1160m, 1138s, 1108w, 1087m, 1067s, 1049s, 1021m, 992s, 972w, 939m, 921w, 8 93s, 8 8 0s,
863m, 8 52m, 8 38m, 758s. 1H-NMR: 7.12 7.09 (m, HÀC(7)); 7.08( d, J ˆ 7.6, HÀC(5)); 6.89 (td, J ˆ 7.4, 1.1,
HÀC(6)); 6.83 (dd, J ˆ 8.2, 0.8, HÀC(8)); 4.83 4.78 ( m, HÀC(5')); 3.29 (dd, J ˆ 10.0, 4.9, 1 HÀC(4')); 3.09
3.03 (m, 1 HÀC(4)); 2.91 2.86 (m, 1 HÀC(4)); 2.87 (t, J ˆ 10.0, 1 HÀC(4')); 2.43 2.39 (m, 1 HÀC(3)); 2.35
2.30 (m, 1 HÀC(3)); 1.45 (d, J ˆ 6.1, Me). 13C-NMR: 152.8( s, C(8a)); 129.0 (d, C(5)); 127.4 (d, C(7)); 121.3 (s,
C(4a)); 121.2 (d, C(6)); 117.3 (d, C(8)); 116.2 (s, C(2)); 79.0 (d, C(5')); 39.6 (t, C(4')); 33.3 (t, C(3)); 24.2 (t,
.
‡
C(4)); 18.9 (q, Me). EI-MS: 222 (21, M ), 149 (11), 148(100), 120 (43), 91 (12), 74 (11). Anal. calc. for
C12H14O2S (222.31): C 64.83, H 6.35, S 14.42; found: C 64.96, H 6.59, S 14.59.
Crystals of 10 suitable for the X-ray crystal-structure determination were grown from Et2O/MeOH.

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Helvetica Chimica Acta Vol. 87 (2004)
Data of 11: 1H-NMR (300 MHz): 4.71 4.58( m, HÀC(5')); 1.55 (d, J ˆ 6.1, Me); the other signals at 7.12
7.07, 6.90 6.80, 3.32 2.85; 2.48 2.29 overlap with those of 10.
4.2. With (R)-2-Phenyloxirane (6). Reaction of 9 (328mg, 2 mmol) with 6 (360 mg, 3 mmol) and 4.5 g of
SiO2 at r.t., 3 d, CC (SiO2, hexane/Et2O 10 :1), and HPLC (Nucleosil 100-7 column, hexane/t-BuOMe 150 :1)
yielded 200 mg (35%) of (2R,4'S)- and 38mg (7%) of (2S,4'S)-3,4-dihydro-4'-phenylspiro[1-benzopyran-
2(2H),2'-[1,3]oxathiolane] (12 and 13, resp., Scheme 5).
23
D
Data of 12: Colorless crystals. M.p. 63.4 65.88. ‰aŠ ˆ À154.6 (89% ee). IR (KBr): 3081w, 3061w, 3028w,
2975w, 2942m, 2884w, 2844w, 1608w, 1600w, 1581s, 1487s, 1454s, 1440m, 1429m, 1347m, 1332w, 1303m, 1272m,
1235s, 1209s, 1145s, 1108s, 1068s, 1035s, 1013m, 98 7s, 938s, 911s, 8 95s, 8 8 s0, 8 61m, 8 36s, 794w, 757s, 742m, 697s.
1H-NMR: 7.40 7.39 (m, 2 arom. H of Ph); 7.33 7.31 (m, 2 arom. H of Ph); 7.27 7.24 (m, 1 arom. H of Ph);
7.14 7.11 (m, HÀC(7)); 7.09 (d, J ˆ 7.5, HÀC(5)); 6.91 (td, J ˆ 7.4, 1.1, HÀC(6)); 6.88 (dd, J ˆ 8.2, 0.9,
HÀC(8)); 4.86 (dd, J ˆ 5.9, 1.9, HÀC(4')); 4.78( dd, J ˆ 9.3, 6.0, 1 HÀC(5')); 4.40 (dd, J ˆ 9.2, 2.0, 1 HÀC(5'));
3.15 3.10 (m, 1 HÀC(4)); 2.94 2.89 (m, 1 HÀC(4)); 2.60 2.55 (m, 1 HÀC(3)); 2.51 2.46 (m, 1 HÀC(3)).
13C-NMR: 152.9 (s, C(8a)); 142.4 (s, 1 arom. C of Ph); 129.2 (d, C(5)); 128.9 (d, 2 arom. CH of Ph); 127.8( d, 1
arom. CH of Ph); 127.7 (d, C(7)); 127.4 (d, 2 arom. CH of Ph); 121.7 (d, C(6)); 121.4 (s, C(4a)); 118.1 (s, C(2));
.
‡
117.5 (d, C(8 )); 77.6 (t, C(5')); 53.2 (d, C(4')); 33.0 (t, C(3)); 24.4 (t, C(4)). EI-MS: 284 (7, M ), 149 (11), 148
(100), 137 (10), 136 (79), 135 (52), 120 (69), 119 (14), 105 (10), 104 (99), 103 (45), 92 (11), 91 (52), 78(48), 77
(24). Anal. calc. for C17H16O2S (284.37): C 71.80, H 5.67, S 11.28; found: C 72.07, H 5.88, S 11.06.
23
D
Data of 13: Colorless oil. ‰aŠ ˆ ‡44.4 (90% ee). IR (film): 3062w, 3028w, 2972w, 2936w, 2847w, 1601w,
1583m, 1489s, 1455s, 1349w, 1302w, 1274w, 1236m, 1211s, 1195s, 1156w, 1110s, 1070m, 1052s, 1038s, 1026s, 98 8s,
937w, 914m, 8 93m, 8 8 0s, 8 58w, 8 37w, 758s, 700s. 1H-NMR: 7.53 (d, J ˆ 7.3, 2 arom. H of Ph); 7.35 (t-like, J ꢀ 7.6, 2
arom. H of Ph); 7.28( t-like, J ꢀ 7.6, 1 arom. H of Ph); 7.16 7.14 (m, HÀC(7)); 7.10 (d, J ˆ 7.5, HÀC(5)); 6.95
6.91 (m, HÀC(8), HÀC(6)); 4.94 (dd, J ˆ 10.4, 6.6, HÀC(4')); 4.54 (dd, J ˆ 9.4, 6.7, 1 HÀC(5')); 4.36 (dd, J ˆ
10.3, 9.5, 1 HÀC(5')); 3.10 3.07 (m, 1 HÀC(4)); 2.93 2.89 (m, 1 HÀC(4)); 2.51 2.40 (m, 2 HÀC(3)).
13C-NMR: 152.9 (s, C(8a)); 137.3 (s, 1 arom. C of Ph); 129.3 (d, C(5)); 128.9 (d, 2 arom. CH of Ph); 128.7 (d, 2
arom. CH of Ph); 128.2 (d, 1 arom. CH of Ph); 127.7 (d, C(7)); 121.7 (d, C(6)); 121.5 (s, C(4a)); 118.2 (s, C(2));
.
‡
117.6 (d, C(8 )); 77.3 (t, C(5')); 55.0 (d, C(4')); 33.2 (t, C(3)); 24.2 (t, C(4)). EI-MS: 284 (14, M ), 149 (11), 148
(97), 137 (11), 136 (91), 135 (47), 120 (56), 119 (11), 105 (11), 104 (100), 103 (39), 91 (36), 78(33), 77 (16).
5. Reactions of 14. 5.1. With (S)-2-Methyloxirane (2). Reaction of 14 (232 mg, 2 mmol) with 2 (232 mg,
4 mmol) and 4.5 g of SiO2 at 08, 2 d; CC (SiO2, hexane/Et2O/Et3N 10 :1 :0.1) yielded 230 mg (66%) of a mixture
of (2S,5R)- and (2S,5S)-2-methyl-1,6-dioxa-4-thiaspiro[4.5]decane (15 and 16, resp.). Separation of the two
diastereoisomers by MPLC (SiO2; hexane/AcOEt 15 :1) gave 100 mg (29%) of 15. Further purification by
HPLC (Nucleosil 100-7 column, hexane/AcOEt/Et3N 45 :1:0.05) yielded 30 mg (9%) of 15, but 16 was obtained
only in 90% purity because of its partial epimerization to 15. Repetition of the reaction of 14 (116 mg, 1 mmol)
with 2 (116 mg, 2 mmol) at 08 for 2 d yielded 63% of 15, 22% of 16, and 15% of 3,4,5,6-tetrahydro-2H-pyran-2-
one (17) according to the 1H-NMR analysis of the reaction mixture and 1,1,2,2-tetrachloroethane as a standard
(Scheme 6).
23
Data of 15: Colorless oil. ‰aŠ ˆ ‡202.1 (> 99% ee). IR (film): 2963s, 2937s, 2862s, 1465m, 1452m, 1440m,
D
1381m, 1354m, 1282m, 1256w, 1230w, 1211m, 1185s, 1165m, 1147s, 1115m, 1092m, 1075s, 1037s, 1021s, 975m,
940m, 925w, 8 99m, 8 71m, 8 56m, 8 13m, 756w. 1H-NMR: 4.65 4.59 (m, HÀC(2)); 3.94 3.90 (m, 1 HÀC(7));
3.78 3.74 ( m, 1 HÀC(7)); 3.11 (dd, J ˆ 9.9, 5.0, 1 HÀC(3)); 2.76 (t, J ˆ 10.0, 1 HÀC(3)); 2.08 1.98 ( m,
2 HÀC(10)); 1.94 1.88 (m, 1 HÀC(9)); 1.66 1.60 (m, 1 HÀC(9)); 1.58 1.52 ( m, 2 HÀC(8)); 1.44 (d, J ˆ 6.2,
Me). 13C-NMR: 118.1 (s, C(5)); 78.3 (d, C(2)); 65.1 (t, C(7)); 39.0 (t, C(3)); 37.4 (t, C(10)); 24.7 (t, C(8)); 22.5 (t,
‡
C(9)); 19.2 (q, Me). CI-MS (NH3): 177 (5), 176 (10), 175 (100, [M ‡ H] ), 118(39). Anal. calc. for C 8H14O2S
(174.26): C 55.14, H 8.10, S 18.40; found: C 55.25, H 8.25, S 18.30.
23
1
Data of 16: Colorless oil. ‰aŠ ˆ À136.8( > 99% ee; containing 10% of 15). H-NMR (C6D6): 4.33 4.28
D
(m, HÀC(2)); 3.83 3.73 (m, 2 HÀC(7)); 2.71 2.65 (m, 2 HÀC(3)); 2.11 2.01 (m, 2 HÀC(10)); 1.62 1.56 (m,
1 HÀC(9)); 1.44 1.37 (m, 1 HÀC(9)); 1.24 1.18( m, 1 HÀC(8)); 1.23 (d, J ˆ 6.2, Me); 1.14 1.09 (m,
1 HÀC(8)). 13C-NMR (C6D6): 120.5 (s, C(5)); 81.8 (d, C(2)); 66.1 (t, C(7)); 38.4 (t, C(3)); 38.2 (t, C(10)); 25.4 (t,
‡
C(8)); 23.2 (t, C(9)); 21.7 (q, Me). CI-MS (NH3): 176 (9), 175 (100, [M ‡ H] ), 118(21).
5.2. With (R)-2-Phenyloxirane (6). Reaction of 14 (232 mg, 2 mmol) with 6 (360 mg, 3 mmol) and 4.5 g of
SiO2 at r.t., 11 h, CC (SiO2; hexane/Et2O/Et3N 10 :1:0.1), and MPLC (SiO2; hexane/Et2O 20 :1) yielded 257 mg
(54%) of (3S,5S)-, 50 mg (11%) of (3S,5R)-3-phenyl-1,6-dioxa-4-thiaspiro[4.5]decane (18 and 19, resp.), and
36 mg (8%) of (2R,5R)-2-phenyl-1,6-dioxa-4-thiaspiro[4.5]decane (20; Scheme 7).
23
D
Data of 18: Colorless crystals. M.p. 49.3 51.48. ‰aŠ ˆ À168.7 (95% ee). IR (KBr): 3071w, 3028w, 3006w,
2962s, 2940s, 2924s, 2878s, 2846m, 1602w, 1494m, 1456s, 1437m, 1378w, 1363w, 1352s, 1342m, 1305w, 1286m,

Helvetica Chimica Acta Vol. 87 (2004)
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1278s, 1263m, 1245w, 1203s, 1186s, 1171m, 1148s, 1129s, 1077w, 1061s, 1048s, 1016s, 959s, 942s, 930s, 8 98s, 8 68s,
846w, 8 34m, 8 20m, 8 02w, 763s, 698s. 1H-NMR: 7.38 7.36 ( m, 2 arom. H); 7.31 7.28( m, 2 arom. H); 7.24 7.22
(m, 1 arom. H); 4.65 (dd, J ˆ 6.1, 1.5, HÀC(3)); 4.62 (dd, J ˆ 9.0, 6.0, 1 HÀC(2)); 4.33 (dd, J ˆ 9.0, 1.7,
1 HÀC(2)); 3.98 3.94 ( m, 1 HÀC(7)); 3.83 3.79 (m, 1 HÀC(7)); 2.27 2.23 (m, 1 HÀC(10)); 2.20 2.16 (m,
1 HÀC(10)); 1.98 1.94 ( m, 1 HÀC(9)); 1.71 1.64 (m, 1 HÀC(9)); 1.61 1.57 (m, 2 HÀC(8)). 13C-NMR: 143.0
(s, 1 arom. C); 128.6 (d, 2 arom. CH); 127.4 (d, 1 arom. CH); 127.2 (d, 2 arom. CH); 119.6 (s, C(5)); 76.9 (t, C(2));
65.3 (t, C(7)); 52.3 (d, C(3)); 36.7 (t, C(10)); 24.6 (t, C(8)); 22.4 (t, C(9)). CI-MS (NH3): 238(11), 237 (76, [ M ‡
‡
H] ), 119 (6), 118(100). Anal. calc. for C 13H16O2S (236.33): C 66.07, H 6.82, S 13.57; found: C 66.06, H 6.85, S
13.35.
23
D
Data of 19: Colorless crystals. M.p. 74.4 74.78. ‰aŠ ˆ ‡69.0 (90% ee). IR (KBr): 3074w, 3027w, 2968w,
2941m, 2880w, 2853w, 1600w, 1491w, 1453w, 1439w, 1377w, 1361w, 1351w, 1335w, 1282w, 1278w, 1263w, 1202w,
1189w, 1155w, 1130m, 1061m, 1055m, 1013s, 969w, 955m, 928m, 8 97m, 8 68w, 8 58w, 8 36w, 8 16w, 760m, 704m,
696m. 1H-NMR: 7.46 7.44 (m, 2 arom. H); 7.33 7.30 (m, 2 arom. H); 7.27 7.24 (m, 1 arom. H); 4.84 (dd, J ˆ
10.3, 6.8, HÀC(3)); 4.51 (dd, J ˆ 9.3, 6.7, 1 HÀC(2)); 4.20 (dd, J ˆ 10.3, 9.4, 1 HÀC(2)); 4.05 4.01 (m,
1 HÀC(7)); 3.92 3.88 (m, 1 HÀC(7)); 2.17 2.13 (m, 1 HÀC(10)); 2.09 2.05 (m, 1 HÀC(10)); 1.96 1.91 (m,
1 HÀC(9)); 1.69 1.57 (m, 1 HÀC(9), 2 HÀC(8)). 13C-NMR: 138.0 (s, 1 arom. C); 128.6 (d, 2 arom. CH); 128.4
(d, 2 arom. CH); 127.8( d, 1 arom. CH); 119.9 (s, C(5)); 76.7 (t, C(2)); 65.1 (t, C(7)); 54.1 (d, C(3)); 36.9 (t,
‡
C(10)); 24.6 (t, C(8)); 22.2 (t, C(9)). CI-MS (NH3): 238(14), 237 (100, [ M ‡ H] ), 118(70), 101 (6). Anal. calc.
for C13H16O2S (236.33): C 66.07, H 6.82, S 13.57; found: C 65.96, H 7.01, S 13.49.
Crystals of 19 suitable for the X-ray crystal-structure determination were grown from Et2O/hexane.
23
D
Data of 20: Colorless crystals. M.p. 55.6 56.98. ‰aŠ ˆ À21.0 (97% ee). IR (KBr): 3068w, 3025w, 2987w,
2968w, 2941m, 2924m, 2891m, 2857m, 1488w, 1462w, 1454m, 1441w, 1422w, 1385w, 1347w, 1325w, 1308w, 1290w,
1260w, 1215m, 1205m, 1184s, 1155m, 1126m, 1070s, 1035s, 1019vs, 1000m, 990s, 948m, 940s, 914w, 907w, 8 8 s7,
871s, 8 47m, 8 11s, 767s, 739m, 700s. 1H-NMR: 7.47 7.45 (m, 2 arom. H); 7.36 7.34 (m, 2 arom. H); 7.31 7.28( m,
1 arom. H); 5.30 (dd, J ˆ 9.8, 6.1, HÀC(2)); 4.06 4.02 (m, 1 HÀC(7)); 3.96 3.91 (m, 1 HÀC(7)); 3.24 3.19
(m, 2 HÀC(3)); 2.17 2.08( m, 2 HÀC(10)); 1.95 1.91 (m, 1 HÀC(9)); 1.66 1.56 (m, 1 HÀC(9), 2 HÀC(8)).
13C-NMR: 139.9 (s, 1 arom. C); 128.7 (d, 2 arom. CH); 128.4 (d, 1 arom. CH); 126.8( d, 2 arom. CH); 119.7 (s,
C(5)); 87.6 (d, C(2)); 66.4 (t, C(7)); 39.1 (t, C(3)); 37.4 (t, C(10)); 24.9 (t, C(8)); 22.7 (t, C(9)). CI-MS (NH3): 238
‡
(8), 237 (49, [M ‡ H] ), 135 (13), 118(100).
Crystals of 20 suitable for the X-ray crystal-structure determination were grown from Et2O/MeOH.
6. X-Ray Crystal-Structure Determination of 3, 7, 8, 10, 19, and 20 (Table and Figs. 1 4)3). All
measurements were performed on a Nonius KappaCCD diffractometer [17] with graphite-monochromated
MoKa radiation (l 0.71073 ä) and an Oxford Cryosystems Cryostream 700 cooler. The data collection and
refinement parameters are given in the Table, and views of the molecules are shown in Figs. 1 4. Data reduction
was performed with HKL Denzo and Scalepack [18]. The intensities were corrected for Lorentz and
polarization effects, and an absorption correction based on the multi-scan method [19] was applied. The
structures were solved by direct methods using SIR92 [20], which revealed the positions of all non-H-atoms. The
non-H-atoms were refined anisotropically. All of the H-atoms were placed in geometrically calculated positions
and refined using a riding model where each H-atom was assigned a fixed isotropic displacement parameter with
a value equal to 1.2 Ueq of its parent C-atom (1.5 Ueq for the Me group in 3 and 10). The refinement of each
structure was carried out on F2 by full-matrix least-squares procedures, which minimized the function Sw(Fo2
F2c )2. A correction for secondary extinction was applied in the cases of 10, 19, and 20. In 3, one reflection, whose
intensitiy was considered to be an extreme outliner, was omitted from the final refinement. Refinement of the
absolute structure parameter [21] yielded values of À 0.1(2), À 0.04(6), 0.05(8), 0.03(7), À 0.05(7), and 0.01(7)
for 3, 7, 8, 10, 19, and 20, resp., which confidently confirms that the refined coordinates represent the true
enantiomorph in each case except for 3, which, due to the low precision, does not give an unambiguous
indication of the correct absolute configuration. Neutral atom scattering factors for non-H-atoms were taken
from [22a], and the scattering factors for H-atoms were taken from [23]. Anomalous dispersion effects were
included in Fc [24]; the values for f' and f'' were those of [22b]. The values of the mass attenuation coefficients
are those of [22c]. All calculations were performed with the SHELXL97 [25] program.
3
)
CCDC-235086-235091 contain the supplementary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK (fax: ‡ 44-(0)1223-336033; e-mail:
deposit@ccdc.cam.ac.uk).

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Received April 1, 2004