Chiral synthesis of cyclopropanes. Stereoselective [2 + 1] cycloaddition reactions of 1-seleno-2-silylethenes with di-(-)-menthyl ethene-1,1- dicarboxylates

Article abstract of DOI:10.1021/jo9820925

Reaction of 1-seleno-2-silylethenes 1 with the chiral electrophiles 2, 3, and 4 derived from (-)-menthol, in the presence of zinc halides gave the cyclopropane products 5, 6, and 7, respectively, with high diastereoselectivity. The absolute configuration of 5a, prepared by the reaction of 1-(phenylseleno)-2-(trimethylsilyl)ethene (1a) and di-(-)- menthyl methylenemalonate (2), was determined to be 2S by conversion to the known chiral compound 11. The proposed mechanism, involving fixation of the (-)-menthyl group to the C=C plane by the Lewis acid in the addition step, is consistent with the experimental observations. A selenium-participating secondary orbital interaction in the synclinal addition path was elucidated by ab initio calculations and explained the observed diasteroselectivity.

Full text of DOI:10.1021/jo9820925

J . Org. Chem. 1999, 64, 2367-2374
2367
Ch ir a l Syn th esis of Cyclop r op a n es. Ster eoselective [2 + 1]
Cycloa d d ition Rea ction s of 1-Selen o-2-silyleth en es w ith
Di-(-)-m en th yl Eth en e-1,1-d ica r boxyla tes
Shoko Yamazaki,* Hitomi Kataoka, and Shinichi Yamabe*
Department of Chemistry, Nara University of Education, Takabatake-cho, Nara 630-8528, J apan
Received October 19, 1998
Reaction of 1-seleno-2-silylethenes 1 with the chiral electrophiles 2, 3, and 4 derived from (-)-
menthol, in the presence of zinc halides gave the cyclopropane products 5, 6, and 7, respectively,
with high diastereoselectivity. The absolute configuration of 5a , prepared by the reaction of
1-(phenylseleno)-2-(trimethylsilyl)ethene (1a ) and di-(-)-menthyl methylenemalonate (2), was
determined to be 2S by conversion to the known chiral compound 11. The proposed mechanism,
involving fixation of the (-)-menthyl group to the CdC plane by the Lewis acid in the addition
step, is consistent with the experimental observations. A selenium-participating secondary orbital
interaction in the synclinal addition path was elucidated by ab initio calculations and explained
the observed diasteroselectivity.
In tr od u ction
bonyl compounds.7 Accordingly, there is a need for
methods that would effect such an addition to R,â-
unsaturated carbonyl compounds. This is because the
resulting and highly substituted cyclopropanes, including
carbonyl groups, are endowed with functional diversity
and are potentially useful for further elaboration.
We have recently reported the development of various
Lewis acid-mediated reactions of (E)-1-(phenylseleno)-2-
silylethenes (1) with R,â-unsaturated carbonyl com-
pounds to afford cyclopropane products.8 These reactions
have high stereoselectivity, and it was proposed that they
involve a selenium-stabilized silicon migration and also
involve a Se- - -CdO secondary orbital interaction in the
first synclinal addition step. The stereochemistry adopted
in the first addition step appears to be retained through-
out the reaction course, leading to the high stereoselec-
The construction of chiral cyclopropane derivatives is
of continuing interest, since cyclopropane moieties are
present in a large number of natural products and
biologically active compounds.1 In addition, chiral cyclo-
propanes are used as synthons in the synthesis of chiral
carbocycles having other ring sizes by utilizing their
unique structural and reactivity properties.2,3 Numerous
synthetic methods for the preparation of chiral cyclopro-
panes have been developed.4 The most generally used
methods are Simmons-Smith reactions5 and metal-
catalyzed decomposition of diazo compounds in the pres-
ence of alkenes.6 However, there are relatively few
methods available for asymmetric synthesis of chiral
cyclopropanes involving addition to R,â-unsaturated car-
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1995, 2, 511. For recent examples, see: (b) FR900848: Yoshida, M.;
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Marshall, V. P. J . Am. Chem. Soc. 1995, 117, 10629. (d) Curacin A:
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Baier, H.; Frank, G.; Du¨rner, G. Liebigs Ann. Chem. 1982, 1999. (c)
Baier, H.; Du¨rner, G.; Quinkert, G. Helv. Chim. Acta 1985, 68, 1054.
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Schmalz, H.-G.; Dzierzynski, E. M.; Du¨rner, G.; Bats, J . W. Angew.
Chem., Int. Ed. Engl. 1986, 25, 992.
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1994, 35, 8939. (b) Corey, E. J .; Grant, T. G. Tetrahedron Lett. 1994,
35, 5373. (c) Romo, D.; Romine, J . L.; Midura, W.; Meyers, A. I.
Tetrahedron 1990, 46, 4951. (d) Schotten, T.; Boland, W.; J aenicke, L.
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Org. Chem. 1997, 62, 3390. (d) Takahashi, H.; Yoshikawa, M.;
Shibasaki, M.; Ohno, M.; Imai, N.; Kobayashi, S. Tetrahedron 1995,
51, 12013. (e) Denmark, S. E.; O’Connor, S. P. J . Org. Chem. 1997,
62, 584. (f) Imai, N.; Sakamoto, K.; Maeda, M.; Kouge, K.; Yoshizane,
K.; Nokami, J . Tetrahedron Lett. 1997, 38, 1423. (g) Kitajima, H.; Ito,
K.; Aoki, Y.; Katsuki, T. Bull. Chem. Soc. J pn. 1997, 70, 207.
(6) (a) Mu¨ller, P.; Baud, C.; Ene, D.; Motallebi, S.; Doyle, M. P.;
Brandes, B. D.; Dyatkin, A. B.; See, M. M. Helv. Chim. Acta 1995, 78,
459. (b) Denmark, S. E.; Stavenger, R. A.; Faucher, A.-M.; Edwards,
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R.; Lake, D. H.; Kong, N.; Fall, M. J . J . Am. Chem. Soc. 1996, 118,
6897. (d) Davies, H. M. L.; Bruzinski, P. R.; Fall, M. J . Tetrahedron
Lett. 1996, 37, 4133. (e) Doyle, M. P.; Zhou, Q.-L.; Charnsangavej, C.;
Longoria, M. A.; McKervey, M. A.; Garcia, C. F. Tetrahedron Lett. 1996,
37, 4129. (f) Doyle, M. P.; Austin, R. E.; Bailey, A. S.; Dwyer, M. P.;
Dyatkin, A. B.; Kalinin, A. V.; Kwan, M. M. Y.; Liras, S.; Oalmann, C.
J .; Pieters, R. J .; Protopopova, M. N.; Raab, C. E.; Roos, G. H.; Zhou,
Q.-L.; Martin, S. F. J . Am. Chem. Soc. 1995, 117, 5763. (g) Doyle, M.
P.; Peterson, C. S.; Protopopova, M. N.; Marnett, A. B.; Parker, D. L.,
J r.; Ene, D.; Lynch, V. J . Am. Chem. Soc. 1997, 119, 8826. (h) Doyle,
M. P.; Dyatkin, A. B.; Kalinin, A. V.; Ruppar, D. A.; Martin, S. F.;
Spallar, M. R.; Liras, S. J . Am. Chem. Soc. 1995, 117, 11021.
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1995, 117, 10393. (b) Pyne, S. G.; Dong, Z.; Skelton, B. W.; White, A.
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10.1021/jo9820925 CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/12/1999

2368 J . Org. Chem., Vol. 64, No. 7, 1999
Yamazaki et al.
Ta ble 1. [2 + 1] Cycloa d d ition Rea ction s of 1-Selen o-2-silyleth en es 1 w ith Di-(-)-m en th yl Meth ylen em a lon a te (2)a
entry
selenosilylethene
Lewis acid
reaction temp (time)
5 + 8, % yield
5:8 ratiob
9,c ee%d
10,c ee%d
1
2
3
4
5
1a
1a
1a
1a
1b
ZnBr2
ZnI2
ZnBr2
ZnI2
ZnI2
-30 °C (180 min), 10 °C (10 min)
-30 °C (180 min), 10 °C (10 min)
-30 °C (90 min), 0 °C (30 min)
-30 °C (90 min), 0 °C (30 min)
-30 °C (180 min), 10 °C (10 min)
56
92
95
99
87
1.4:1
1:1
1.9:1
1.8:1
1:1.5
86
77
80
81
79
61
78
74
68
84
a
b
All reactions were carried out in with 1 mmol of 1, ca. 2.6 mmol of 2, and 1.5 mmol of ZnX2 in CH2Cl2 (2 mL). 5:8 ratio was determined
1
1
by H NMR. c 9 and 10 were isolated in ca. 50% total (9 + 10) yield. The ratio of 9:10 was similar to the 5:8 ratio determined by H NMR.
d
ee% was determined by HPLC using a chiral column (CHIRALCEL OF).
tivity . Since the first addition step is similar to that in
concerted Diels-Alder reactions, the asymmetric induc-
tion methodology commonly employed in Diels-Alder
reactions9 can potentially be applied. Previously, we
attempted asymmetric [2 + 1] cycloaddition reactions of
1 and vinyl ketones in the presence of a BINOL ((R)- or
(S)-1,1′-binaphthol)-derived chiral titanium Lewis acid.
However, the reactions only gave cyclopropanes with
relatively low, although reproducible, enantioselectivity.8c
As part of further efforts to develop this [2 + 1] cycload-
dition reaction leading to efficient asymmetric cyclopro-
panation, we have now found and report herein that
reaction of 1 with the chiral electrophiles 2, 3, and 4,
containing (-)-menthyl ester moieties in the presence of
a Lewis acid (ZnX2), gave cyclopropane products 5, 6, and
7 with high diastereoselectivity (eq 1).
b oxyla t es. Ethene-1,1-dicarboxylates such as methyl-
enemalonates and 2-carbonyl-substituted ethene-1,1-
dicarboxylates have been shown to have high reactivity
toward (E)-1-(phenylseleno)-2-silylethenes (1) in the pres-
ence of ZnBr2.8b,d Since highly diastereoselective Lewis
acid-mediated Diels-Alder reactions of di-(-)-menthyl
methylenemalonates have been reported,10 (-)-menthyl
esters 2-4 are attractive substrates for diastereoselective
[2 + 1] cycloaddition reactions of 1 under Lewis acid
conditions. These reactions were examined as described
in the following discussion.
Reaction of 1a ,b with di-(-)-menthyl methylenema-
lonate (2) in the presence of Lewis acid gave [2 + 1] and
[2 + 2] cycloadducts 5 and 8 (eq 2), similar to the reaction
of the achiral substrates such as di-tert-butyl and di-
methyl methylenemalonates. As a Lewis acid, ZnBr2 was
first examined since the total chemical yield was high in
the case of di-tert-butyl malonate.8b The reaction leads
to a high net yield of the cyclopropane, even though
mixtures of cyclopropane and cyclobutane products re-
sulted. ZnI2 was also examined, and Table 1 summarizes
these reactions (Table 1 containing more data is included
in the Supporting Information).
To a solution of 1 in CH2Cl2 at -78 °C was added the
Lewis acid, followed by 2 in CH2Cl2. Reaction tempera-
ture and time were as shown in Table 1. Quenching with
triethylamine gave a mixture of 5 and 8. The observed
trends for the total yield of 5+8 and the ratio are as
follows. Using the same reaction temperature and time
in the reaction of 1a and 2, ZnBr2 gave a slightly higher
amount of cyclopropane 5 than that of the cyclobutane
8. ZnI2 gave a slightly higher total yield (entries 1,3 vs
In addition, we have analyzed the reaction mechanism
theoretically. The selenium-participating synclinal ad-
dition was carefully examined. So far, there are no
detailed reports which address the synclinal addition and
secondary orbital interactions precisely in terms of
transition state modeling. Since the π facial selectivity
of the addition is essential for the observed high diaste-
reoselectivity, a precise and theoretical examination of
the synclinal addition has been performed as is described
herein.
Resu lts a n d Discu ssion
[2 + 1] Cycloa d d ition Rea ction s of 1-Selen o-2-
silyleth en es w ith Di-(-)-m en th yl Eth en e-1,1-d ica r -
(10) (a) Katagiri, N.; Haneda, T.; Hayasaka, E.; Watanabe, N.;
Kaneko, C. J . Org. Chem. 1988, 53, 227. (b) Katagiri, N.; Haneda, T.;
Watanabe, N.; Hayasaka, E.; Kaneko, C. Chem. Pharm. Bull. 1988,
36, 3867. (c) Loncharich, R. J .; Schwartz, T. R.; Houk, K. N. J . Am.
Chem. Soc. 1987, 109, 14.
(9) For reviews, see (a) Oppolzer, W. Angew. Chem., Int. Ed. Engl.
1984, 23, 876. (b) Masamune, S.; Choy, W.; Peterse, J . S.; Sita, L. R.
Angew. Chem., Int. Ed. Engl. 1985, 24, 1.

Chiral Synthesis of Cyclopropanes
J . Org. Chem., Vol. 64, No. 7, 1999 2369
Ta ble 2. [2 + 1] Cycloa d d ition Rea ction s of 1-Selen o-2-silyleth en e 1a w ith Di-(-)-m en th yl Ester s 3 a n d 4a
entry
dimenthyl ester
Lewis acid
reaction temp (time)
6/7 (% yield)
6/7 de%b
byproduct
recovered 1, % yield
1
2
3
4
5
6
7
8
9
3
3
3
4a
4b
4c
4d
4e
4f
ZnBr2
ZnI2
SnCl4
ZnI2
ZnI2
ZnI2
ZnI2
ZnI2
ZnI2
-30 °C (8 h)
-30 °C (14 h)
-78 °C (1 h)
-30 °C (5.5 h)
-30 °C (8 h)
-30 °C (7 h)
-30 °C (7 h)
-30 °C (8 h)
-30 °C (8 h)
6a (20)
6a (39)
6a (0)
7a (77)
7b (84)
7c (71)
7d (ca. 74)
7e (80)
7f (65)
90
92
62
60
6
9
8
12
23
17
14
14 (86)
ca. 95d
ca. 95d
ca. 95d
ca. 95d
ca. 95d
ca. 95d
a
b
All reactions were carried out with 1 mmol of 1a , 1.3 mmol of 3/4, and 1.5 mmol of ZnX2 in CH2Cl2 (2 mL). de% was determined by
1H NMR. c A mixture of desilylated compounds including 14 was produced but could not be purified. A trace amount of impurity was
d
present, but the structure could not be determined as the corresponding diastereoisomer.
2,4). Higher temperature (+10 °C) reduced the total yield
of 5+8 with ZnBr2, resulting in desilylated byproducts
(entry 1). Use of 1b instead of 1a decreased the ratio of
5 to 8, probably because steric hindrance disturbs the
silicon migration (compare entry 2 with entry 5). Cyclo-
propanes 5a ,b and cyclobutanes 8a ,b could not be
separated by column chromatography. The cycloadducts
5 and 8 were reduced to the corresponding alcohols 9a ,b
and 10a ,b, which were then readily separated (eq 3). The
selectivity of each reaction was examined by measuring
the ee% of 9 and 10 using chiral HPLC. In all cases,
reaction of 1 with a chiral electrophile 2 gave cyclopro-
pane products 5 with high diastereoselectivity (de 77-
88%, deduced from the ee% of 9). The cyclobutane 8
wasalso obtained with modest to high diastereoselectivity
(de 61-84%, deduced from the ee% of 10), with some
excep-tions (see the Supporting Information).
yield.11 Wittig reaction of 12 with methylenetriphen-
ylphosphorane in THF gave 13 in 68% yield. Hydrolysis
and subsequent treatment with diazomethane gave (R)-
(+)-dimethyl vinylcyclopropanedicarboxylate (11) in 77%
yield. The enantiopurity of 11 was determined to be 69-
71% ee by comparison with the reported optical rota-
tion.12 The absolute configuration of 5a was also thereby
confirmed to be 2S.
(eq 4)
Next, reactions of 1a with 2-carbonyl-subsituted ethene-
1,1-dicarboxylates 3 and 4 were examined (eq 5 and Table
2; Table 2 containing more data is in the Supporting
Information). Reactions of 1a with the corresponding
dimethyl or diethyl esters gave cyclopropanes in satisfac-
tory yields.8d However, reaction of 1a with triester olefin
The absolute configuration of 5a was determined by
conversion to the known chiral compound 11 in eq 4, a
useful synthetic intermediate for steroids, prostaglan-
dins, and jasmonates.2 Thus, the 1.8:1 mixture of 5a and
8a , prepared as in entry 4, was oxidized with NaIO4 in a
THF-H2O solution at room temperature. The reaction
mixture was purified by column chromatography to give
the sila-Pummerer product, cyclopropane 12, in 50%
(11) (a) Reich, H. J .; Shah, S. K. J . Org. Chem. 1977, 42, 1773. (b)
Brook, A. G.; Anderson, D. G. Can J . Chem. 1968, 46, 2115. (c) Carey,
F. A.; Hernandez, O. J . Org. Chem. 1973, 38, 2670. (d) Vedejs, E.;
Mullins, M. Tetrahedron Lett. 1975, 2017.
(12) (a) Danishefsky, S.; Rovnyak, G. J . Chem. Soc., Chem. Commun.
1972, 821. (b) Hayashi, T.; Yamamoto, A.; Ito, Y. Tetrahedron Lett.
1988, 29, 669.

2370 J . Org. Chem., Vol. 64, No. 7, 1999
Yamazaki et al.
Sch em e 1
(eq 5)
3 in the presence of ZnBr2 or ZnI2 proceeded sluggishly
with low chemical yield (entries 1 and 2), probably due
to steric hindrance from the menthyl group. Longer
reaction time in the presence of ZnBr2, higher tempera-
ture, or use of a stronger Lewis acid such as SnCl4
resulted in formation of desilylated byproducts, e.g., 14
(entry 3). Reactions of di-(-)-menthyl 2-acylethene-1,1-
dicarboxylates 4 with 1a were next examined. The
starting olefins 4 were conveniently prepared by reaction
of di-(-)-menthyl oxomalonate (15) and acyl-substituted
triphenylmethylenephosphoranes 16 (eq 6).13 We found
that reactions of di-(-)-menthyl 2-acylethene-1,1-dicar-
(eq 6)
cross-peak between H2 and H3 in 2D-NOESY.15 The
determination of configurations of 6 and 7 by conversion
to other useful chiral molecules is currently under
investigation in our group.
boxylates 4 with 1a proceeded faster than those with
triester 3 (entries 4-9). Thus, reaction of 4 with 1a in
the presence of ZnI2 at -30 °C in CH2Cl2 for 5.5-8 h gave
7 in 62-84% yield with ca. 95% purity.14 It should be
noted that the terminal vinyl group of 4e did not
participate in the cycloaddition reaction (entry 8).
Th eor etica l Stu d y of th e Rea ction Mech a n ism
To account for the diastereoselective [2 + 1] cycload-
dition reaction of 1 and chiral ethene-1,1-dicarboxylates,
the [2 + 1] cycloaddtion mechanism was theoretically
studied and the similarity with Lewis acid promoted
Diels-Alder reactions was investigated. The total reac-
tion mechanism was proposed as shown in Scheme 1.8
The reaction involves a Se- - -CdO secondary orbital
interaction in the first synclinal addition step, and also
involves a selenium-stabilized silicon migration in the
Reactions of 1a with olefins 3 and 4 gave C2,C3-cis-
substituted cyclopropanes 6 and 7, respectively, and no
cyclobutanes were produced, similar to reactions of 1 with
the corresponding dimethyl or diethyl esters.8d The C2,C3-
cis stereochemistry of 6 and 7 was detemined by a NOE
(13) 16a -c were prepared from R-chloro/bromo ketones and tri-
phenylphosphine and subsequent treatment with NaHCO3. (a) Ramirez,
F.; Dershowitz, S. J . Org. Chem. 1957, 22, 41. 16d -f were prepared
from the reaction of acetomethylenetriphenylphosphorane (16a ), n-
BuLi, and alkyl halides according to the literature procedure. (b)
Taylor, J . D.; Wolf, J . F. J . Chem. Soc., Chem. Commun. 1972, 876. (c)
Cooke, M. P., J r. J . Org. Chem. 1973, 38, 4082.
(15) The origin of C2,C3-cis selectivity of 6 and 7 probably arises
from the larger LUMO coefficient of C4 than that of C5 in 3-ZnX2 or
4-ZnX2 complexes, which was shown for the corresponding trimethyl
ester.8d
(14) A trace amount of impurity was present, but the structure could
not be determined to be the corresponding diastereoisomer.

Chiral Synthesis of Cyclopropanes
J . Org. Chem., Vol. 64, No. 7, 1999 2371
Sch em e 2. Th e π F a cia l Ster eoch em istr y for th e
Dia ster eoselectivity of Cyclop r op a n es 5-7
Figure 1, both menthyl groups are fixed by chelation with
ZnBr2. A C2 symmetry axis exists with respect to the C1d
C3 double bond. The ester carbonyl (C4dO1) is syn-
periplanar to the O2-C7 bond, and the H-C7 bond is
almost syn-periplanar to the C4-O2 bond. In Figure 1,
the proposed synclinal approaches of 1a from the si face
and re face of C2 to 2-ZnBr2 are outlined, where C4- - -
Se and C3- - -C2 distances are set to 3.7 and 3.5 Å,
respectively, as the initial complex prior to the transition
state in the addition step. These distances are taken from
calculated results of the model system (see the Support-
ing Information). Approach from the re face of C2 results
in steric repulsion between Se and the isopropyl carbon
of the menthyl group. This proposed diastereoselection
is similar to that observed in asymmetric Diels-Alder
reactions involving (-)-menthyl acrylates.3,19 The stere-
ochemistry controlled in the first addition step seems to
be retained throughout the reaction, leading to high
stereoselectivity. Thus, attack from the si-side with
respect to C2 finally leads to (2S)-5a in the reaction of
1a and 2 according to the mechanism shown in Scheme
1.20 This proposed mechanism is consistent with the
experimental observation of the absolute stereochemistry
of the product 5a by conversion to 11 (eq 4). Although
the absolute configurations of 6 and 7 have not been
determined yet, the observed high diastereoselectivity
suggests the stereoselective pathway shown in Scheme
2 for the [2 + 1] cycloaddition of 1a , and 3 and 4.
F igu r e 1. Proposed approaches of 1a to 2-ZnBr2. For the
structures of 1a and 2-ZnBr2, RHF/3-21G* optimized bond
lengths and bond angles are used. They are shown in Figure
5S of the Supporting Information. C3---C2 and C4---Se distances
are set to 3.5 and 3.7 Å, respectively, as an initial complex in
the addition step. These distances are taken from the model
system (see Figure 2S in the Supporting Information).
resulting zwitterionic intermediate. Using model calcula-
tions, we have determined the structure of the weakly
interacting system composed of 1 and 2-ZnBr2 as the
complex prior to the transition state.16,17 Such weakly
interacting systems are also known in Lewis-acid pro-
moted Diels-Alder reactions.18
The structures of 1a and 2-ZnBr2 were fully optimized
(see Figure 1 and the Supporting Information). In the
optimized structure of 2-ZnBr2 shown at the top of
(16) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T.; Petersson,
G. A.; Montgomery, J . A.; Raghavachari, K.; Al-Laham, M. A.;
Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.; Cioslowski, J .;
Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala,
P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts,
R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .;
Stewart, J . J . P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A. Gaussian
94, Revision B.1, Gaussian, Inc., Pittsburgh, PA, 1995. MO calculations
using Gaussian 94 were made on the CONVEX SPP1200/XA at the
Information Processing Center (Nara University of Education).
(17) A detailed discussion of the ab initio calculations is presented
in the Supporting Information.
In the case of chiral triester-substituted olefin 17 (eq
7), the Lewis acid is bidentately coordinated to two
ethoxycarbonyl groups and the (-)-menthoxycarbonyl
group may be not fixed in the CdC plane.8d As a result,
(19) Recently, we reported the diastereoselective reaction of 1a and
(-)-menthyl 2-(dimethylphosphono)acrylate in the presence of SnCl4.
Yamazaki, S.; Takada, T.; Imanishi, T.; Moriguchi, Y.; Yamabe, S. J .
Org. Chem. 1998, 63, 5919.
(18) Yamabe, S.; Dai, T.; Minato, T. J . Am. Chem. Soc. 1995, 117,
10994.
(20) The configuration of C6 of 5a was assumed as S, following the
previous discussion on the relative stereochemistry of C2-C6.8b

2372 J . Org. Chem., Vol. 64, No. 7, 1999
Yamazaki et al.
0.042 (s, 9H × 0.36), 0.602 (d, J ) 6.8 Hz, 6H), 0.704-1.19
(m, 18H), 1.31-1.73 (m, 8H + 2H × 0.64), 1.93-2.25 (m, 4H
+ 1H × 0.64 + 2H × 0.36), 2.40 (d, J ) 12.7 Hz, 1H × 0.64),
2.76 (m, 1H × 0.36), 4.35 (d, J ) 10.5 Hz, 1H × 0.36), 4.68-
4.88 (m, 2H), 7.27-7.31 (m, 3H), 7.61-7.67 (m, 2H); IR (neat)
2922, 2870, 1717, 1580 cm-1; MS (EI) m/z 648; exact mass M+
648.3091 (calcd for C35H56O4SeSi 648.3113).
Di-(-)-m en th yl 2-(1-(P h en ylselen o)-1-(tr ieth ylsilyl)m eth -
yl)cyclop r op a n e-1,1-d ica r boxyla te (5b) a n d Di-(-)-m en -
th yl 2-(P h en ylselen o)-3-(tr im eth ylsilyl)cyclobu ta n e-1,1-
d ica r boxyla te (8b) (en tr y 5 in Ta ble 1). 5b and 8b were
obtained as a 1:1.5 mixture (Rf ) 0.5 (hexane-ether ) 9:1));
1H NMR (200 MHz, CDCl3) δ (ppm) 0.474-0.593 (m, 6H),
0.658-1.21 (m, 33H), 1.25-2.28 (m, 12H + 3H × 0.4 + 2H ×
0.6), 2.50 (d, J ) 12.5 Hz, 1H × 0.4), 2.75 (m, 1H × 0.6), 4.40
(d, J ) 9.3 Hz, 1H × 0.6), 4.61-4.89 (m, 2H), 7.22-7.26 (m,
3H), 7.56-7.67 (m, 2H); IR (neat) 2920, 1717, 1580 cm-1; MS
(EI) m/z 690; exact mass M+ 690.3552 (calcd for C38H62O4SeSi
690.3583).
(eq 7)
the diastereoselectivity was low (de 33%). Thus, fixation
of the (-)-menthyl group by the Lewis acid in the addition
step is presumed to be critical for the diastereoselective
[2 + 1] cycloadditions of 1 with (-)-menthol-based chiral
electrophilic olefins.
P r ep a r a tion of 9 a n d 10 (en tr y 4 in Ta ble 1). LiAlH4
(79 mg, 2.09 mmol) was slowly added to a solution of a mixture
of 5a and 8a (1.8:1) (300 mg, 0.46 mmol) in anhydrous diethyl
ether (5.9 mL) with stirring at 0 °C. The mixture was allowed
to warm to room temperature and stirred for 4.5 h. Saturated
Na2SO4 solution was added to the stirred mixture with ice-
cooling. The mixture was extracted with ether. The aqueous
layer was acidified by 1 N HCl and extracted with ether. The
combined organic phase was dried (MgSO4) and evaporated
in vacuo. The residue was purified by column chromatography
over silica gel eluting with hexanes-ether (1:4) to give 9a (53
mg, 30%) (Rf ) 0.4) and 10a (40 mg, 23%) (Rf ) 0.6).
2,2-Bis(h yd r oxym et h yl)-1-[(p h en ylselen o)(t r im et h yl-
silyl)m eth yl]cyclop r op a n e (9a ). HPLC (hexane-iPrOH )
9:1) major peak tR1 38.6 min, minor peak tR2 81.6 min, 81%
ee. The 1H NMR spectrum was in accord with the reported
In summary, we have shown new diastereoselective
cyclopropanation reactions of 1-seleno-2-silylethene 1
with di-(-)-menthyl ethene-1,1-dicarboxylates 2-4 in the
presence of zinc halides. The absolute stereochemistry
of cycloadduct 5a was determined by conversion to the
known chiral compound 11. The stereochemical outcome
of this reaction is consistent with a selective addition step
in the proposed mechanism, as shown using ab initio
calculations. Thus, the readily available and inexpensive
(-)-menthol is a suitable chiral auxiliary in this [2 + 1]
cycloaddition reaction. Further work is in progress on the
utilization of these chiral highly functionalized cyclopro-
panes.
data.;8b [R]28.4 -9.3 (c 0.66, CHCl3).
D
4,4-Bis(h yd r oxym eth yl)-1-(p h en ylselen o)-2-(tr im eth yl-
silyl)cyclobu ta n e (10a ). HPLC (hexane-iPrOH ) 9:1) major
peak tR1 18.1 min, minor peak tR2 29.1 min, 68% ee. The 1H
Exp er im en ta l Section
NMR spectrum was in accord with the reported data.;8b [R]24.7
+34.1 (c 1.0, CHCl3).
D
Gen er a l Meth od s. Melting points are uncorrected. IR
spectra were recorded in the FT mode. H NMR spectra were
1
2,2-Bis(h ydr oxym eth yl)-1-[(ph en ylselen o)(tr ieth ylsilyl)-
m eth yl]cyclop r op a n e (9b). (Rf ) 0.4 (hexane-ether ) 1:4).
Pale yellow oil; HPLC (hexane-iPrOH ) 9:1) major peak tR1
30.6 min, minor peak tR2 52.1 min, 79% ee; 1H NMR (200 MHz,
CDCl3) 0.348 (dd, J ) 5.4, 5.4 Hz, 1H), 0.559-0.683 (m, 6H),
0.866-0.972 (m, 10H), 1.24 (ddd, J ) 12.8, 8.0, 5.4 Hz, 1H),
2.17 (d, J ) 12.8 Hz, 1H), 2.50 (bs, 1H), 2.95 (bd, J ) 9.0 Hz,
1H), 3.44-3.87 (m, 4H), 7.24-7.30 (m, 3H), 7.61-7.66 (m, 2H);
13C NMR (50.1 MHz, CDCl3) δ 3.317, 7.609, 18.79, 26.15, 29.77,
30.09, 64.49, 69.86, 128.0, 129.1, 129.3, 135.0; IR (neat) 3400,
2956, 2878, 1578 cm-1; MS (EI) m/z 386; exact mass M+
recorded in CDCl3 at 200 or 400 MHz. 13C NMR spectra were
recorded in CDCl3 at 50.1 or 100.6 MHz. Chemical shifts are
reported in ppm relative to Me4Si or residual nondeuterated
solvent. Mass spectra were recorded at an ionizing voltage of
70 eV by EI or FAB. HPLC analysis was performed with a
UV detector (detection, 254 nm light) and a flow rate of 0.5
mL/min using a CHIRALCEL OF (0.46 cm × 25 cm). Optical
rotations were measured with a cylindrical 1 cm i.d. × 10 cm
or 0.33 cm i.d. × 10 cm cell. All reactions were carried out
under a nitrogen atmosphere.
Di-(-)-m en th yl 2-(1-(P h en ylselen o)-1-(tr im eth ylsilyl)-
m eth yl)cyclop r op a n e-1,1-d ica r boxyla te (5a ) a n d Di-(-)-
m en th yl 2-(P h en ylselen o)-3-(tr im eth ylsilyl)cyclobu ta n e-
1,1-d ica r boxyla te (8a ). 2 was prepared according to the
literature.10b 2 could not be purified from traces of remaining
starting di-(-)-menthyl malonate, and the mixture was used
in the reaction.
A Typ ica l Exp er im en ta l P r oced u r e (en tr y 4 in Ta ble
1). To a solution of 1a (255 mg, 1.0 mmol) in dichloromethane
(2.0 mL) cooled to -78 °C was added ZnI2 (479 mg, 1.5 mmol)
followed by a solution of 2 (1.021 g, ca. 2.6 mmol including a
small amount of di-(-)-menthyl malonate) in dichloromethane
(0.5 mL). The mixture was allowed to warm to -30 °C and
stirred for 90 min and then at 0 °C for 30 min. The reaction
mixture was quenched by triethylamine (0.36 mL, 2.37 mmol),
and then saturated aqueous NaHCO3 was added to the
mixture. The mixture was extracted with dichloromethane,
and the organic phase was washed with water, dried (Na2SO4),
and evaporated in vacuo. The residue was purified by column
chromatography over silica gel eluting with hexanes-ether (9:
1) to give a mixture of 5a and 8a (638 mg, 99%). 5a and 8a
were obtained as a 1.8:1 mixture (Rf ) 0.4 (hexane-ether )
9:1)); 1H NMR (200 MHz, CDCl3) δ (ppm) 0.009 (s, 9H × 0.64),
386.1181 (calcd for C18H30O2SeSi 386.1180); [R]30.4 -5.5 (c
D
0.21, CHCl3).
4,4-Bis(h yd r oxym eth yl)-1-(p h en ylselen o)-2-(tr ieth ylsi-
lyl)cyclobu ta n e (10b). (Rf ) 0.6 (hexane-ether ) 1:4). Pale
yellow oil; HPLC (hexane-iPrOH ) 9:1) major peak tR1 17.9
min, minor peak tR2 29.2 min, 84% ee; 1H NMR (400 MHz,
CDCl3) 0.578 (q, J ) 8.0 Hz, 6H), 0.962 (t, J ) 8.0 Hz, 9H),
1.72-1.74 (m, 2H), 1.95 (ddd, J ) 11.0, 9.9, 9.9 Hz, 1H), 3.64
(s, 2H), 3.81 (d, J ) 11.7 Hz, 1H), 3.84 (d, J ) 11.0 Hz, 1H),
4.21 (d, J ) 11.7 Hz, 1H), 7.24-7.29 (m, 3H), 7.53-7.55 (m,
2H); 13C NMR (100.6 MHz, CDCl3) δ 2.423, 7.642, 23.13, 26.74,
44.91, 50.28, 67.56, 69.28, 127.4, 129.4, 131.1, 133.0; IR (neat)
3380, 2950, 2876, 1578 cm-1; MS (EI) m/z 386; exact mass M+
386.1175 (calcd for C18H30O2SeSi 386.1180); [R]25.3 +20.3 (c
D
0.54, CHCl3).
Di-(-)-m en th yl 2-F or m ylcyclop r op a n e-1,1-d ica r boxyl-
a te (12). To a solution of a mixture of 5a and 8a (1.8:1)
(prepared as in entry 4, Table 1) (621 mg, 0.96 mmol) in THF
(19.2 mL) and water (9.6 mL) was added NaIO4 (1.03 g, 4.8
mmol) with vigorous stirring. The mixture was stirred for 6 h
at room temperature. The reaction mixture was poured into
ether and saturated aqueous NaHCO3 solution and extracted
with ether (×2). The combined organic layer was washed with

Chiral Synthesis of Cyclopropanes
J . Org. Chem., Vol. 64, No. 7, 1999 2373
water, dried (MgSO4), and concentrated in vacuo. The residue
was purified by column chromatography over silica gel eluting
with hexanes-ether (3:1) to give 12 (208 mg, 50%). (Rf ) 0.4
(hexane-ether ) 3:1)). Pale yellow oil; 1H NMR (200 MHz,
CDCl3) 0.736 (d, J ) 6.8 Hz, 3H), 0.745 (d, J ) 7.1 Hz, 3H),
0.819-1.18 (m, 18H), 1.21-2.12 (m, 14H), 2.75 (ddd, J ) 8.7,
6.8, 4.9 Hz, 1H), 4.74 (ddd, J ) 10.7, 10.7, 4.3 Hz, 1H), 4.76
2:1); colorless oil; 1H NMR (200 MHz, CDCl3) 0.745 (d, J )
7.0 Hz, 3H), 0.753 (d, J ) 6.8 Hz, 3H), 0.828-1.08 (m, 18H),
1.13-1.71 (m, 8H), 1.83-2.03 (m, 4H), 2.93 (d, J ) 7.6 Hz,
2H), 3.69 (s, 3H), 3.81 (t, J ) 7.6 Hz, 1H), 4.726 (ddd, J )
10.9, 10.9, 4.4 Hz, 1H), 4.733 (ddd, J ) 10.9, 10.9, 4.3 Hz, 1H);
13C NMR (50.1 MHz, CDCl3) δ 15.99, 16.19, 20.78, 20.95, 22.03,
22.99, 23.29, 25.65, 26.12, 31.35, 33.10, 34.18, 40.46, 40.54,
46.79, 46.85, 48.31, 52.02, 75.82, 167.9, 168.1, 171.3; IR (neat)
2950, 2870, 1734, 1456, 1412, 996, 915, 845, 733 cm-1; MS
(ddd, J ) 10.9, 10.9, 4.2 Hz, 1H), 9.22 (d, J ) 4.9 Hz, 1H); 13
C
NMR (50.1 MHz, CDCl3) δ 15.70, 16.14, 19.17, 20.87, 22.00,
22.09, 22.88, 23.20, 25.71, 26.06, 31.40, 34.15, 34.91, 37.89,
40.52, 40.66, 46.71, 47.08, 76.63, 165.5, 167.6, 196.3; IR (neat)
2960, 2872, 1727 cm-1; MS (EI) m/z (relative intensity) 435
(30) M+ + 1, 419 (15), 297 (100); [R]17.5D -19.2 (c 0.80, CHCl3).
Di-(-)-m en th yl 2-Vin ylcyclop r op a n e-1,1-d ica r boxyla te
(13). A solution of n-BuLi (1.25 M in n-hexane, 0.99 mL, 1.24
mmol) was added dropwise to a stirred and ice-cold suspension
of methyltriphenylphosphonium iodide (443 mg, 1.24 mmol)
in THF (4.2 mL). The mixture was stirred to 0 °C for 15 min.
A solution of 12 (208 mg, 0.48 mmol) in THF (1.4 mL) was
added to the mixture at 0 °C. After the mixture was allowed
to warm to room temperature, it was stirred for 2.5 h. Water
was added, and the mixture was extracted with ether. The
ether layer was separated, dried (MgSO4), and concentrated
in vacuo. The residue was purified by column chromatography
over silica gel eluting with hexanes-ether (9:1) to give 13 (141
mg, 68%) (Rf ) 0.8 (hexane-ether ) 9:1)). Colorless oil; 1H
NMR (400 MHz, CDCl3) 0.707 (d, J ) 6.8 Hz, 3H), 0.747 (d, J
) 7.0 Hz, 3H), 0.849-0.927 (m, 14H), 0.956-1.09 (m, 4H),
1.21-1.53 (m, 6H), 1.64-1.70 (m, 4H), 1.83-1.94 (m, 2H),
2.04-2.08 (m, 2H), 2.56 (ddd, J ) 7.9, 7.9, 8.2 Hz, 1H), 4.70
(ddd, J ) 10.6, 10.6, 4.4 Hz, 1H), 4.72 (ddd, J ) 10.6, 10.6, 4.3
Hz, 1H), 5.09 (dd, J ) 10.0, 1.6 Hz, 1H), 5.29 (dd, J ) 17.0,
1.6 Hz, 1H), 5.40 (ddd, J ) 17.0, 10.0, 8.2 Hz, 1H); 13C NMR
(100.6 MHz, CDCl3) δ 16.08, 16.50, 20.24, 20.83, 22.10, 22.17,
23.21, 23.65, 26.33, 30.66, 31.48, 34.37, 34.42, 36.56, 40.92,
46.98, 47.32, 75.60, 75.81, 118.0, 133.7, 167.1, 169.6; IR (neat)
2950, 2872, 1717, 1640, 984, 913 cm-1; MS (EI) m/z 432; MS
(FAB) m/z 453 (MH+); [R]17.6 -59.9 (c 0.8, CHCl3).
D
1,1-Di-(-)-m en th yl 2-Meth yl Eth en e-1,1,2-tr ica r boxyl-
a te (3). A solution containing 1,1-di-(-)-menthyl 2-methyl
ethane-1,1,2-tricarboxylate (19) (1.81 g, 4.0 mmol) in carbon
tetrachloride (7.5 mL) was treated with azobis(isobutyronitrile)
(3.7 mg). Bromine (918 mg, 5.75 mmol) was added to the
mixture in small portions with irradiation by a 100 V-60 W
lamp. The addition rate was adjusted so that hydrogen
bromide was evolved at a steady rate. After the addition,
stirring and irradiation was continued for 16 h. The reaction
mixture was concentrated in vacuo to give crude 1,1-di-(-)-
menthyl 2-methyl 1-bromoethane-1,1,2-tricarboxylate. The
crude bromide (2.355 g) was dissolved in anhydrous ether (8.5
mL) and was cooled to 0 °C. Triethylamine (425 mg, 4.20
mmol) in ether (3.2 mL) was then added dropwise to the
bromide solution. After the addition, the reaction mixture was
stirred for 16 h at 0 °C. Water was added to the mixture, and
the formed triethylamine hydrobromide salt was dissolved. The
mixture was extracted with ether, and the ether extracts were
dried (MgSO4) and evaporated in vacuo. The residue was
purified by column chromatography over silica gel eluting with
hexanes-ether (4:1) to give 3 (1.63 g, 91%). 3: Rf ) 0.7
(hexane-ether ) 2:1); colorless oil; 1H NMR (200 MHz, CDCl3)
0.74-1.15 (m, 24H), 1.32-1.88 (m, 8H), 1.99-2.26 (m, 4H),
3.78 (s, 3H), 4.86 (ddd, J ) 11.2, 11.2, 4.3 Hz, 1H), 4.91 (ddd,
J ) 11.1, 11.1, 4.3 Hz, 1H), 6.84 (s, 1H); 13C NMR (50.1 MHz,
CDCl3) δ 15.93, 20.75, 21.86, 21.98, 22.99, 25.42, 25.94, 31.32,
34.09, 40.11, 40.52, 46.79, 47.03, 52.19, 76.14, 76.49, 128.8,
139.4, 161.8, 163.7; IR (neat) 2950, 2868, 1730, 1653 cm-1; MS
(EI) m/z 450; exact mass M+ 450.2949 (calcd for C26H42O6
(FAB) m/z 433 (MH+); [R]18.0 -28.6 (c 0.89, CHCl3).
D
Dim eth yl 2-Vin ylcyclop r op a n e-1,1-d ica r boxyla te (11).
A mixture of 13 (534 mg, 1.23 mmol), NaOH (978 mg, 17.4
mmol), and a spatula of hydroquinone in H2O (1.7 mL) and
EtOH (3.4 mL) was heated for 8 h under reflux. The reaction
mixture was concentrated in vacuo, and water was added. The
mixture was washed with ether (×3). The water phase was
saturated with NaH2PO4‚2H2O and concentrated hydrochloric
acid was added to adjust to pH ) 5 with ice-cooling. The
aqueous solution was extracted with ether (×6), and the ether
extracts were dried (MgSO4) and concentrated in vacuo. The
residue was dissolved in ether (20 mL), and the solution was
treated with excess diazomethane in ether. The reaction
mixture was concentrated in vacuo. The residue was purified
by column chromatography over silica gel eluting with hex-
anes-ether (9:1) to give 11 (175 mg, 77%) (Rf ) 0.4). 11: Pale
450.2982); [R]19.3 -69.4 (c 1.0, CHCl3).
D
P r ep a r a tion of Olefin s 4. A typical experimental proce-
dure is described for the preparation of 4a .
1,1-Di-(-)-m en t h yl 2-Acet ylet h en e-1,1-d ica r b oxyla t e
(4a ). To an ice-water-cooled solution of di-(-)-menthyl ox-
omalonate (413 mg, 1.0 mmol) in benzene (2.0 mL) was added
1-triphenylphosphoranylidene-2-propanone (318 mg, 1.0 mmol).
After stirring for 2.5 h at room temperature, benzene was
evaporated and ether was added. The precipitates were
removed by filtration. The filtrate was concentrated and the
residue was purified by column chromatography over silica gel
eluting with cyclohexane-CH2Cl2 (3:1) to give 4a (410 mg,
94%). 4a : (Rf ) 0.5 (cyclohexane-CH2Cl2 ) 3:1)). Colorless
crystals; mp 70-73 °C; 1H NMR (400 MHz, CDCl3) 0.762 (d, J
) 6.8 Hz, 3H), 0.845 (d, J ) 6.8 Hz, 3H), 0.882-1.12 (m, 18H),
1.36-1.58 (m, 4H), 1.68-1.73 (m, 4H), 1.81-1.86 (m, 1H),
2.00-2.05 (m, 2H), 2.24-2.28 (m, 1H), 2.35 (s, 3H), 4.86 (ddd,
J ) 10.9, 10.9, 4.5 Hz, 1H), 4.91 (ddd, J ) 10.9, 10.9, 4.4 Hz,
1H), 7.09 (s, 1H); 13C NMR (100.6 MHz, CDCl3) δ 16.04 (q),
16.14 (q), 20.98 (q), 21.02 (q), 22.05 (q), 22.17 (q), 23.19 (t),
23.23 (t), 25.67 (d), 26.14 (d), 30.73 (q), 31.55 (d), 34.28 (t),
34.31 (t), 40.17 (t), 40.75 (t), 47.07 (d), 47.22 (d), 76.38 (d), 76.78
(d), 135.4 (d), 136.2 (s), 162.6 (s), 164.4 (s), 196.1 (s). 13C
multiplicities were determined by DEPT; IR (KBr) 2962, 2872,
1736, 1698, 1630 cm-1; MS (EI) m/z 434; exact mass M+
434.3020 (calcd for C26H42O5 434.3032); Anal. Calcd for
1
yellow oil; H NMR (400 MHz, CDCl3) 1.59 (dd, J ) 9.2, 5.0
Hz, 1H), 1.72 (dd, J ) 7.6, 5.0 Hz, 1H), 2.58 (ddd, J ) 9.2, 8.3,
7.6 Hz, 1H), 3.74 (s, 3H), 5.12-5.16 (m, 1H), 5.26-5.32 (m,
1H), 5.40-5.49 (m, 1H); 13C NMR (100.6 MHz, CDCl3) δ 20.58,
31.42, 35.79, 52.53, 52.68, 118.6, 133.0, 167.8, 170.0; IR (neat)
3014, 2958, 1729, 1640, 990, 919 cm-1; MS (EI) m/z 184; exact
mass M+ 184.0735 (calcd for C9H12O4 184.0735); [R]17.6D +38.2
(c 1.1, CCl4).
1,1-Di-(-)-m en th yl 2-Meth yl Eth a n e-1,1,2-tr ica r boxyl-
a te (19). Sodium hydride (0.74 g, 57% dispersion in oil, 17.6
mmol, washed twice with hexane) was suspended in freshly
distilled THF (35 mL). After the mixture was cooled to 0 °C,
di-(-)-menthyl malonate (3.31 g, 8.69 mmol) in THF (2.3 mL)
was added dropwise over 10 min. After 30 min, methyl
chloroacetate (943 mg, 8.69 mmol) dissolved in THF (5.4 mL)
was added dropwise, and the mixture was allowed to room
temperature and stirred overnight. Water was added to the
reaction, the mixture was extracted with ether, and the organic
phase was dried (MgSO4). The solvent was evaporated in
vacuo. The residue was purified by column chromatography
over silica gel eluting with hexanes-ether (19:1 to 9:1) to give
the title compound (1.66 g, 42%). Rf ) 0.8 (hexane-ether )
C
26H42O5: C, 71.85; H, 9.74. Found: C, 71.69; H, 9.68; [R]33.9
D
-82.0 (c 0.97, CHCl3).
Typ ica l Exp er im en ta l P r oced u r e for Cycloa d d ition s
w ith 3 a n d 4 (en tr y 2 in Ta ble 2). To a solution of 1a (255
mg, 1.0 mmol) in dichloromethane (2.0 mL) cooled to -78 °C
was added ZnI2 (479 mg, 1.5 mmol) followed by a solution of
3 (586 mg, 1.3 mmol) in dichloromethane (0.5 mL). The
mixture was allowed to warm to -30 °C and stirred for 14 h.
The reaction mixture was quenched by triethylamine (0.36 mL,
2.37 mmol), and then saturated aqueous NaHCO3 was added

2374 J . Org. Chem., Vol. 64, No. 7, 1999
Yamazaki et al.
to the mixture. The mixture was extracted with dichlo-
romethane, and the organic phase was washed with water,
dried (Na2SO4), and evaporated in vacuo. The residue was
purified by column chromatography over silica gel eluting with
cyclohexane-CH2Cl2 (4:1) to give 6a (273 mg, 39%, de 92%).
peaks δ 15.93, 16.11, 20.60, 20.69, 21.89, 23.05, 23.29, 25.77,
25.91, 26.06, 31.20, 31.26, 34.03, 40.28, 40.75, 46.71, 46.79,
49.65, 52.28, 53.39, 54.00, 75.52, 75.73, 125.7, 126.8, 127.5,
128.9, 129.2, 132.6, 166.8, 166.9, 171.1.; IR (neat) 2932, 2872,
1730, 1609, 1580 cm-1; MS (EI) m/z 634; exact mass M+
634.2755 (calcd for C34H50O6Se 634.2773); Anal. Calcd for
C34H50O6Se: C, 64.44; H, 7.95. Found: C, 64.28; H, 8.07.
1
The de% was determined by integration of the H signals at δ
2.74 (major) and δ 2.86 (minor).
1,1-Di-(-)-m en th yl 2-Meth yl 3-[(P h en ylselen o)(tr im eth -
ylsilyl)m eth yl]-2,3-cis-cyclop r op a n e-1,1,2-tr ica r boxyla te
(6a ). (Rf ) 0.6 (hexane-ether ) 4:1)). Pale yellow oil; 1H NMR
(200 MHz, CDCl3) for the major diastereomer -0.081 (s, 9H),
0.754 (d, J ) 6.8 Hz, 3H), 0.788 (d, J ) 6.8 Hz, 3H), 0.837-
1.11 (m, 18H), 1.32-2.14 (m, 12H), 2.20 (dd, J ) 13.2, 9.5 Hz,
1H), 2.74 (d, J ) 9.5 Hz, 1H), 3.19 (d, J ) 13.2 Hz, 1H), 3.68
(s, 3H), 4.77 (ddd, J ) 10.9, 10.9, 4.4 Hz, 2H), 7.20-7.27 (m,
3H), 7.62-7.64 (m, 2H). Selected observed NOE's were be-
Th eor etica l ca lcu la tion s. Ab initio RHF/3-21G* calcula-
tions were performed, using the GAUSSIAN 9416 program
installed at the CONVEX SPP-1200/XA computer (Information
Processing Center, Nara University of Education). Detailed
data and related discussions are included in the Supporting
Information.
Ack n ow led gm en t. We are grateful to Dr. K. Yama-
moto (Osaka University) for measurement of mass
spectral data. This work was supported by the Grant-
in-Aid for Scientific Research on Priority Area No.
10125226 from the Ministry of Education, Science,
Sports and Culture, of the J apanese Government.
1
tween δ 2.20 (H3) and 2.74 (H2) (see H numbering in Scheme
1) and between δ 3.19 and 7.62-7.64.; 13C NMR (50.1 MHz,
CDCl3) for the major diastereomer δ -1.646, 15.90, 16.14,
21.04, 21.30, 22.09, 22.21, 22.82, 23.20, 24.07, 25.39, 26.00,
31.46, 31.52, 33.59, 34.27, 36.19, 40.40, 40.49, 40.81, 47.00,
47.17, 51.96, 75.84, 76.66, 127.6, 128.7, 129.4, 135.8, 164.3,
168.5, 168.9; IR (neat) 2930, 2344, 1730, 1578 cm-1; MS (EI)
m/z 706; exact mass M+ 706.3191 (calcd for C37H58O6SeSi
Su p p or tin g In for m a tion Ava ila ble: The detailed version
of Tables 1 and 2, the product characterization data for 4b-f,
6b (which appears in the detailed version of Table 2 in the
Supporting Information) and 7a -f, 1H NMR spectra for
compounds 3, 4b,c, 6a ,b, 7a -c, 7e,f, 9b, 10b, 11-13, and 20,
and results of theoretical analyses using ab initio calculations.
This material is available free of charge via the Internet at
http://pubs.acs.org.
706.3168); [R]20.2 -108.6 (c 1.0, CHCl3).
D
14. Yield 86% (entry 3 in Table 2). (9:1 trans-cis isomers)
(Rf ) 0.4 (hexane-ether ) 4:1). Pale yellow oil; 1H NMR (200
MHz, CDCl3) for the major trans isomer) 0.736 (d, J ) 6.6 Hz,
6H), 0.819-1.05 (m, 18H), 1.21-1.96 (m, 12H), 3.70 (s, 3H),
3.73-3.87 (m, 2H), 4.63-4.77 (m, 2H), 5.73 (ddd, J ) 15.4,
6.5, 2.6 Hz, 1H), 6.74 (d, J ) 15.4 Hz, 1H), 7.27-7.31 (m, 3H),
7.43-7.48 (m, 2H); 13C NMR (50.1 MHz, CDCl3) for major
J O9820925