Enantioselective cyclopropanation reactions with planar-chiral pyridinium ylides: A substituent effect and a remote steric effect

Article abstract of DOI:10.1002/adsc.201000079

Novel planar-chiral pyridinium ylides were designed, and generated in situ from the corresponding pyridinium salts with triethylamine. Ylides with a common parapyridinophane skeleton reacted efficiently with electron-deficient dicyanoalkenes, or malononit

Full text of DOI:10.1002/adsc.201000079

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DOI: 10.1002/adsc.201000079
Enantioselective Cyclopropanation Reactions with Planar-Chiral
Pyridinium Ylides: A Substituent Effect and a Remote Steric
Effect
Nobuhiro Kanomata,a,c,* Ryo Sakaguchi,a Kazuki Sekine,b Satomi Yamashita,b
and Hiroko Tanakaa
a
Department of Chemistry and Biochemistry, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan
Fax : (+81)-3-5286-3487; e-mail: kanomata@waseda.jp
Department of Applied Chemistry, Meiji University, Kawasaki, Kanagawa 214-8571, Japan
N.K. used to be a faculty member of Meiji University (1999–2005)
b
c
Received: January 29, 2010; Revised: October 2, 2010; Published online: November 12, 2010
Dedicated to Professor Tadashi Nakata on the occasion of his 65th birthday.
Abstract: Novel planar-chiral pyridinium ylides
were designed, and generated in situ from the cor-
responding pyridinium salts with triethylamine.
Ylides with a common parapyridinophane skeleton
reacted efficiently with electron-deficient dicyanoal-
kenes, or malononitriles, to produce optically active
cyclopropane derivatives with high enantioselectivi-
ty (up to 99% ee). Remote steric effects were ob-
served on the enantioselectivities, where the R2
groups of the pyridinophane core resulted in higher
ee values of the products. Density function theory
(DFT) calculations are in good agreement with our
experimental results: the energetically favored tran-
sition state leads to the major stereoisomer, namely
the trans-cyclopropane products.
sufficient and aryl-conjugated alkenes,[3–9] or by gener-
ating ylide reagents such as sulfur ylides,[10,11] ammoni-
um ylides,[12] and pyridinium ylides[13,14] to effect addi-
tion–elimination processes with electron-deficient al-
kenes that behave as Michael acceptors. As a repre-
sentative method for the non-metallic synthesis,
Kojima and Ohkata et al. reported a highly diastereo-
selective cyclopropanation reaction (dr=98/2) with
exclusive trans-selectivity, achieved by reaction of a
malononitrile derivative with an optically active pyri-
dinium ylide A, generated in situ from the corre-
sponding a-pyridinium acetamide.[13] Recently,
Yamada et al. demonstrated an enantioselective cyclo-
propanation reaction (er up to 96/4) with pyridinium
ylide B, whose phenyl group on its chiral auxiliary
shields one side of the pyridinium ring as a result of
cation-p interactions.[14]
Keywords: cyclophanes; cyclopropanes; enantiose-
lectivity; heterocycles; planar chirality; ylides
As one of our long-term research projects on
planar-chiral molecules,[15–20] we previously reported
that the bridged NADH model C achieved highly
enantioselective reduction of a-keto esters, with up to
99% ee, mimicking the LDH reduction of pyruvate to
Optically active cyclopropanes are attractive organic lactate.[15] In these reactions, the ansa-bridge plays a
molecules in terms of both their biological activities key role in controlling the biomimetic reactions, en-
and their unique reactivities.[1] A number of chemists suring that they occur on the opposite side of the
have been studying asymmetric cyclopropanation re- bridge and, therefore, effecting stereospecific transfer
actions[2] by reacting metal carbenoids with electron- of hydrogen from the dihydropyridine core to the sub-
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Enantioselective Cyclopropanation Reactions with Planar-Chiral Pyridinium Ylides
strate. Such functionality inspired us to design a new
Table 1 summarizes the asymmetric cyclopropana-
class of pyridinium ylides D, whose planar chirality tion reactions of various electron-deficient alkenes
would induce stereoselective transfer of a carbon 16q–z with planar-chiral pyridinium ylides generated
atom bonding directly to its pyridine nitrogen. Anoth- from 9a–e. Initially, we carried out the reaction of 2-
er interesting aspect is the remote steric effect of the benzylidenemalononitrile (16q) with the pyridinium
R2 groups at C-3, the bulkiness of which would signifi- salt 9a in the presence of Et3N in dichloromethane at
cantly affect the conformation of the ansa-bridge and, room temperature for 6 h to give an optically active
accordingly, its shielding effects above the vicinity of cyclopropane derivative (2R,3S)-17aq[21] in 98% yield,
the pyridine nitrogen. In this paper, we describe with a moderate selectivity of 50% ee (entry 1). None
highly enantioselecive cyclopropanation reactions of the cis-isomer was observed in this reaction, which
with planar-chiral pyridinium ylides D, whose ansa- is in good agreement with previously reported race-
bridge functions as an excellent inducer of new ste- mic,[22] diastereoselective,[13] and enantioselective cy-
reogenic centers.
clopropanation reactions[14] with pyridinium ylides.
Scheme 1 depicts the syntheses of a series of pyridi- The reaction of 2-neopentylidenemalononitrile (16r),
nium salts 9–15, via the corresponding pyridine pre- which has a bulky tert-butyl group, with 9a proceeded
cursors 1–7, from planar-chiral bridged nicotinate (S)- enantioselectively to afford the corresponding cyclo-
1, a common starting material for enantiomerically propane 17ar[14,21b] with 98% ee (entry 2). Since the
enriched [10]ACHTUNGTRENNUNG
(2,5)pyridinophane methyl esters.[16] substituent groups proved to be crucial for enantiose-
Conversion of (S)-1 to pyridines 2–7 was performed lection, we then investigated the reactions of 9b–e,
by transformation of the carboxyl group to a methyl bearing various ester moieties, to explore the substitu-
group, N-acyloxazolidinone moieties, or bulkier silyl ent effects of the R1 group that is to be incorporated
ethers with quaternary carbon atoms at the C-3 posi- directly into the cyclopropane product. The reactions
tion. The reactions of 1–7 with 2-bromoacetophenone of the methyl and ethyl esters 9b and 9c were com-
(8a) or bromoacetates 8b–e resulted in formation of plete in 2 h at room temperature, to afford cyclopro-
the corresponding pyridinium salts 9–15, which are panes 17bq[23] and 17cq with 62% and 69% ee, respec-
planar-chiral ylide precursors.
Scheme 1. Synthesis of pyridinium salts 9–15 from pyridinophane methyl ester (S)-1. Conditions: a) 1 equiv. LAH, Et2O,
room temperature, 30 min, quantitative; b) 3 equiv. SOCl2, CHCl3, room temperature, 1 h; c) 1 equiv. LAH, THF, room tem-
perature, 4 h, 84% (two steps); d) LiOH, MeOH-H2O (9/1), room temperature, overnight, 97%; e) (COCl)2, CHCl3, room
temperature, 1.5 h; f) 2 equiv. (S)- or (R)-4-benzyloxazolidin-2-one (BnOx), 5 equiv. NaH, CH2Cl2, room temperature, 4–
20 h, 70% and quantitative (two steps) for 3 and 4, respectively; g) 3 equiv. RLi (R=Me, Ph, or Bu), THF, À208C, 1.5–15 h,
quantitative; h) 1.5 equiv. TMSCl, 3 equiv. imidazole, CH2Cl2, room temperature, 2–19 h, 80—99%; i) 5 or 10 equiv. 8a–e,
MeCN, 508C, 12 h.
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Table 1. Cyclopropanation reactions of planar-chiral ylides generated from 9a–e with 16q–z.
Entry
Pyridinium
R1
Malononitrile
R3
Time [h]
Cyclopropane
Yield [%][a]
Pyridinophane 2
9
16
17
ee [%][b]
Yield [%]a)
1
2
3
4
5
6
7
8
a
a
b
c
d
e
e
e
e
e
e
e
e
e
Ph
Ph
MeO
EtO
BnO
t-BuO
t-BuO
t-BuO
t-BuO
t-BuO
t-BuO
t-BuO
t-BuO
t-BuO
q
r
q
q
q
q
s
Ph
t-Bu
Ph
Ph
Ph
Ph
2-furyl
2-thienyl
p-ClC6H4
p-MeOC6H4
o-FC6H4
o-ClC6H4
o-MeOC6H4
o-tolyl
6
6
2
2
3
1.5
6
4
5
2
4
2
6
aq
ar
bq
cq
dq
eq
es
98
74
86
70
82
98
86
88
64
90
81
92
62
87
50[c,d]
98[c,e]
62[f,g]
69[c,g]
45[f,g]
94[f,g]
73[f,h]
90[i,j]
75
98
89
76
90
96
92
92
74
74
85
95
67
66
t
et
9
u
v
w
x
y
z
eu
ev
ew
ex
ey
ez
94[f,g]
92[k,g]
96[l,g]
98[c,m]
96]m,n]
99[h,o]
10
11
12
13
14
4
[a]
Isolated yields.
[b]
Enantiomeric excesses were measured by HPLC using a chiral stationary phase (Daicel Chemical Industries, Ltd.). Flow
rate is 1.0 mLminÀ1 unless otherwise stated.
CHIRALCEL OD.
[c]
[d]
[e]
[f]
IPA/hexane (1/5) (1.5 mLminÀ1).
IPA/hexane (1/15) (1.5 mLminÀ1).
CHIRALPAK AD-H.
IPA/hexane (1/9).
[g]
[h]
[i]
IPA/hexane (1/19).
CHIRALPAK IA.
THF/hexane (1/19).
CHIRALPAK AS-H.
CHIRALCEL OJ-H.
IPA/hexane (1/99).
CHIRALPAK IC.
CHIRALCEL OD-H.
[j]
[k]
[l]
[m]
[n]
[o]
tively (entries 3 and 4), but the benzyl ester 9d pro- nitrile (16s) gave 17es with 73% ee (entry 7), other al-
duced 17dq with merely 45% ee (entry 5). kenes 16t–z, with 2-thienyl, o,p-chlorophenyl, o,p-me-
In contrast, the enantioselectivity of the cyclopro- thoxyphenyl, o-fluoro, and o-tolyl groups, provided
panation reaction with tert-butyl ester 9e was signifi- the corresponding compounds 17et–ez with more than
cantly enhanced under similar reaction conditions, 90% ee (entries 8–14). In particular, the o-substituted
giving (1R,3S)-tert-butyl 2,2-dicyano-3-phenylcyclo- phenyl groups of 16w–z achieve extremely high enan-
propanecarboxylate (17eq) in 98% yield, with an ex- tioselectivity to give 17ew–ez with 96–99% ee (en-
cellent enantiomeric excess of 94%, as well as pyridi- tries 11–14).
nophane 2 recovery in 96% yield (entry 6). These re-
Since the bulkiness of the ester moieties is of signif-
sults revealed that the ester moieties strongly influ- icant importance in the above-mentioned cyclopropa-
ence the stereoselectivities, and the sterically demand- nation reactions, we expected steric interaction be-
ing tert-butyl ester turned out to be the most tween the R1 groups and the pyridinophane ansa-
effective.
bridges to be a key factor in controlling the enantiose-
We then examined the scope of the asymmetric cy- lectivity. To test this working hypothesis, we next fo-
clopropanation by the reactions of various alkenes cused attention on identifying the substituent effects
16s–z with 9e. Although 2-(2-furylmethylene)malono- of R2 on pyridine that would induce “remote steric ef-
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Enantioselective Cyclopropanation Reactions with Planar-Chiral Pyridinium Ylides
Table 2. Remote steric effects of R2 substituents in asymmetric cyclopropanation reactions.
Entry
Pyridinium salts
Time [h]
Cyclopropane
Yield [%][a]
Pyridinophane
1, 3–7
Yield [%][a]
10–15
R1
R2
17
ee [%][b,c]
1
10a
11a
12a
13a
14a
15a
15a
10b
14b
14c
14d
10e
14e
15e
Ph
Ph
Ph
Ph
Ph
Ph
Ph
MeO
MeO
EtO
BnO
t-BuO
t-BuO
t-BuO
CO2Me
3.5
14
12
17
2
aq
aq
aq
aq
aq
aq
aq
bq
bq
cq
dq
eq
eq
eq
69
91
97
63
89
87
76 (50)
66 (50)
63 (50)
72 (50)
61 (50)
73 (50)
76 (50)
79 (62)
81 (62)
79 (69)
77 (45)
95 (94)
93 (94)
93 (94)
1
3
4
5
6
7
7
1
6
6
6
1
6
7
64
85
91
69
97
96
78
54
2[d]
3[d]
4[d,e]
5
CO-(S)-BnOx
CO-(R)-BnOx
CMe2OTMS
CPh2OTMS
CBu2OTMS
CBu2OTMS
CO2Me
CPh2OTMS
CPh2OTMS
CPh2OTMS
CO2Me
6
3
7[d,e]
8
15
24
2
2
1.5
2
87
24[f]
95
9
94
10
11
12
13
14
96
79
quant.
85
85
quant.
quant.
quant.
84
CPh2OTMS
CBu2OTMS
2
1.5
93
[a]
Isolated yields.
[b]
Enantiomeric excesses were measured by HPLC using a chiral stationary phase (Daicel Chemical Industries, Ltd.). See
Table 1 for conditions.
[c]
[d]
[e]
[f]
The ee values in parentheses are those obtained with 9a–e (R2 =Me) for reference.
LiH was employed instead of Et3N.
Carried out at 08C.
Alkene 16q was recovered in 58% yield.
fects”, or relayed steric interactions, between R2 and excesses of (1R,3S)-17eq reached 93–95% ee, these
the ester groups, mediated by the conformational flex- values being comparable with that obtained with 9e
ibility of the ansa-bridges on the generated ylide in- (entries 12–14).
termediates.
Scheme 2 shows that the remote steric effect was
Asymmetric cyclopropanation reactions exhibiting observed in reactions with some other electron-rich
such effects of R2 are shown in Table 2. As for the re- alkenes such as 16s and 16t; 2-furyl- and 2-thienylcy-
actions of malononitrile 16q with 10a, 11a, and 12a, clopropanes 17es and 17et resulted from the reactions
with a carbonyl group at R2, the enantiomeric excess- with 14e (R1 =t-BuO; R2 =CPh2OTMS), and the se-
es of the resulting cyclopropane (2R,3S)-17aq in- lectivities were improved to 86% and 93% ee, respec-
creased to 63–76% (entries 1–3); the stereochemis- tively, compared with the results obtained for the re-
tries of the 4-benzyloxazolidin-2-one moieties were actions with 9e (73% and 90% ee, respectively). The
found to be less important (entries 2 and 3). Bulkier “remote stereocontrol” effect observed here is worth
substituents incorporating quaternary carbon atoms mentioning as it is a unique property of planar-chiral
generally exhibited better results with 13a and 15a,
providing 17aq with 72–79% ee, except for 14a, where
the ee was 61% ee (entries 4–7). For pyridinium salts
with ester moieties COR1, the remote steric effects in-
duced by 10b and 14b–d (R2 =CO2Me or
CPh2OTMS) had a remarkable influence on the cor-
responding cyclopropanes, which were produced with
higher enantiomeric excesses (77–81% ee) than were
obtained with 9b–d (R2 =Me, 45–69% ee) (entries 8–
Scheme 2. Remote steric effect of 14e (R2 =CPh2OTMS) in
11). For ylides prepared from 10e, 14e, and 15e, incor-
porating a tert-butoxy group for R1, the enantiomeric asymmetric cyclopropanation of 16s and 16t.
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pyridinium ylides for enhancing stereoselectivity, even
though the R2 substituents are apparently located at a
distance from their reaction sites, beyond the bridge,
and, therefore, seem not to be crucial.
The relative structures of the cyclopropane prod-
ucts were unambiguously assigned from their spectro-
scopic data.[24] Their absolute configurations are pro-
posed to be (2R,3S) for 17aq and 17ar, (1R,3S) for
17bq–eq, 17eu, 17ev, and 17ez, and (1R,3R) for 17es,
17et, and 17ew–ey (2-furyl, 2-thienyl, o-fluorophenyl,
o-chlorophenyl, and o-methoxyphenyl groups receive
higher priority than a phenyl group) based on the fol-
lowing CD spectral and/or experimental analyses: (i)
there is good correlation between the line shapes of
the CD spectra for 17ar (R1 =Ph; R3 =t-Bu) and the
known (2R,3S)-17aq (R1, R3 =Ph), and also among
17bq–eq (R1 =MeO, EtO, BnO, or t-BuO; R3 =Ph,
see Figure 1); these findings show that the absolute
configurations of these molecules are identical to one
another; (ii) the CD spectral analyses of some other
cyclopropanes 17eu, 17ev, and 17ex–ez (R1 =t-BuO;
R3 =o,p-ClC6H5, o,p-MeOC6H5, and o-tolyl) showed
that they had structures similar to that of 17eq; (iii)
enantiomerically pure tert-butyl 2,2-dicyano-3-phenyl-
cyclopropanecarboxylate (17eq) was obtained by
simple recrystallization, and its absolute structure was
determined to be the trans-(1R,3S) configuration by
Figure 2. X-ray crystallographic structure of trans-(1R,3S)-
17eq.
Scheme 3. Transformation of optically active cyclopropane
17eq into 17bq. Conditions: a) HCO2H/CH2Cl2 (1/1), room
temperature, 4 d; b) 3 equiv. TMSCHN2, MeOH, room tem-
perature, 6 h; c) SOCl2, reflux, 35 h.
X-ray crystallographic analysis (Figure 2);[25,26] and the remote steric effects increase the enantiomeric ex-
(iv) chemical transformation of (1R,3S)-17eq to cesses of 17es and 17et, but do not decrease the ee
(1R,3S)-17bq via intermediates 18 and 19[24] supports values (Scheme 2), and the cyclopropane 17ew was
an unambiguous structural correlation between these obtained with very high ee as well as other products.
enantiomerically enriched substances (Scheme 3).[27]
These results suggest that the asymmetric cyclopropa-
The absolute configuration of the remaining 17es, nation reactions proceeded through similar transition
17et, and 17ew (R1 =t-BuO; R3 =heteroaromatic and states in the same enantioselective fashion.
o-FC6H4) was eventually assigned to be (1R,3R),
The proposed reaction pathway for obtaining trans-
which is substantially the same as the others because (2R,3S)-17a (R1 =Ph) and trans-(1R,3S)-17b–e (R1 =
MeO, EtO, BnO, and t-BuO) is illustrated in
Scheme 4. Treatment of the pyridinium salts 9–15
under basic conditions generated the corresponding
planar-chiral ylides. An electron-deficient alkene is
principally accessible from the other side of the
shielding ansa-bridge, or less hindered “bottom-side”,
of the ylide, and a reversible reaction occurs to form
adducts E–H. The face selectivities of both ylides and
malononitriles 16 are crucial in determining both the
enantioselectivity and the diastereoselectivity of cis-
and trans-17; four possible combinations of the Re-
face and Si-face of the sp2 carbon of the generated
ylide and malononitrile 16 establish new stereogenic
centers in cyclopropane 17. Irreversible cyclopropane
ring formation occurs mostly from intermediate E or
its rotamer E’, which leads to a major stereoisomer,
namely trans-(2R,3S)-17a or trans-(1R,3S)-cyclopro-
pylcarboxylate, represented by 17eq, whereas such a
ring closure from the intermediate F or F’, leading to
a minor trans-isomer, is less favorable because of
Figure 1. CD spectra of (1R,3S)-cyclopropanecarboxylates
17bq–eq.
steric repulsion between the COR1 or R3 groups and
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Enantioselective Cyclopropanation Reactions with Planar-Chiral Pyridinium Ylides
Scheme 4. Proposed reaction pathways to trans-cyclopropane 17.
the ansa-bridges of the pyridinophane moieties. The against even a small ester group in a TS-F-type transi-
exclusive formation of trans-cyclopropanes is rational- tion state.
ized by the more strained transition states expected
Consequently, asymmetric cyclopropanation reac-
for ring-closing substitution reactions of G and H tions of 2-substituted malononitriles proceeded effi-
(steric interactions of -COR1 vs. R3), which would dis- ciently with planar-chiral pyridinium ylides generated
assemble the intermediates without formation of cis- from 9–15, and, in particular for the ylide generated
cyclopropane 17.
from 9e, exhibited high enantioselectivity, to give op-
Figure 3 illustrates the proposed transition state ge- tically active cyclopropanes with up to 99% ee. These
ometries, TS-E and TS-F, generated from intermedi- results suggest that planar-chiral pyridinophanes are
ates E and F, respectively (R1 =t-BuO, R2 =Me, and excellent for stereoselective carbon atom transfer in
R3 =Ph) for the formation of the major and minor such a series of asymmetric cyclopropanation reac-
trans-cyclopropanes (1R,3S)- and (1S,3R)-17eq DFT tions. The “remote stereocontrol” designed here was
(B2LYP/6-31G**) calculations indicate that the tran- successful in fine-tuning the conformations of pyridi-
sition state TS-E, leading to the major isomer trans- nophane cores to enhance asymmetric induction in
(1R,3S)-17eq, is energetically more favored than TS-F cyclopropanation reactions, without the aid of chiral
(DErel =7.82 kJmolÀ1),[28] leading to the minor isomer auxiliaries. Catalytic cyclopropanation reactions in-
trans-ACHTUNGTRENNUNG(1S,3R)-17eq; this is in good agreement with our volving such pyridinium ylides are now being investi-
experimental results. Apparently, the tert-butyl group gated in our laboratory.
in TS-F is located closer to some methylene units of
the ansa-bridge than is the case in TS-E, and these re-
pulsive interactions increase the TS-F transition state
Experimental Section
energy. It seems that the choice of ester group is so
important primarily because their bulkiness differenti-
ates the pathways for optically active cyclopropanes
with high enantioselectivity. A remote steric effect of
the substituent at C-3 is also expected since the
bridge overhanging the nitrogen side of the pyridine
Synthesis of 3-Methyl[10]ACTHNUTRGENUGN(2,5)parapyridinophane (2)
To a suspension of LiAlH4 (30 mg, 0.792 mmol) in anhy-
drous ether (4 mL) was added a solution of bridged nicoti-
nate (S)-1 (218 mg, 0.792 mmol) in ether (4 mL) at 08C, and
ring would cause a greater repulsive interaction the mixture was stirred at room temperature for 30 min.
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Nobuhiro Kanomata et al.
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Figure 3. Transition state geometries from 9e and 16q, estimated by DFT (B3LYP/6-31G**) calculations: (a) TS-E, leading
to the major isomer trans-(1R,3S)-17eq; and (b) TS-F, leading to trans-(1S,3R)-17eq.
After the reaction was complete, 15% aqueous sodium hy-
droxide (0.2 mL) was added at 08C, followed by addition of
water (0.2 mL). MgSO4 was added and the mixture was fil-
tered through Celite (Hyflo Supercel). After removal of the
on silica gel with ether/hexane (1/1) to give the methyl de-
rivative 2; yield: 154 mg (0.666 mmol, 84%); yellow oil;
1H NMR (399.65 MHz, CDCl3): d=0.21 (m, 1H), 0.46 (m,
1H), 0.74–0.85 (m, 4H), 1.10–1.23 (m, 6H), 1.36 (m, 1H),
1.51 (m, 1H), 1.82 (m, 2H), 2.33 (s, 3H), 2.52 (ddd, J=14.6,
10.3, 4.3 Hz, 1H), 2.63–2.76 (m, 2H), 3.05 (ddd, J=10.7, 6.4,
4.4 Hz, 1H), 7.23 (s, 1H), 8.19 (s, 1H); 13C NMR
(100.40 MHz, CDCl3): d=18.5, 24.5, 25.0, 26.3, 26.5, 26.6,
27.9, 28.0, 28.5, 32.0, 34.3, 130.9, 134.5, 138.1, 146.8, 158.1;
CD (MeCN): lext =276 (De=+8.9), 251 (À3.5), 219
(+11.1); [a]2D0: +80.6 (c 1.0 in CHCl3). HR-MS (FAB+):
m/z=232.2073, calcd. for C16H26N+ [M+H]+: 232.2065;
chiral HPLC analysis [CHIRALCEL OD-H, IPA-hexane
(1/99), flow rate=1.0 mL/min, 258C]: retention times=
7.4 min (R) and 9.8 min (S).
solvent vacuum,
hydroxymethyl[10]ACHTUNGTRENNUNG(2,5)pyridinophane;
under
the
residue
yield:
gave
3-
197 mg,
(0.796 mmol, quantitative); white solid; mp 95.8–97.58C;
1H NMR (399.65 MHz, CDCl3): d=0.19 (m, 1H), 0.43 (m,
1H), 0.60–0.85 (m, 7H), 1.04–1.30 (m, 4H), 1.35–1.56 (m,
2H), 1.75–1.91 (m, 2H), 2.57 (ddd, J=14.1, 9.8, 4.2 Hz, 1H),
2.74 (dt, J=13.8, 5.2 Hz, 1H), 2.80 (dt, J=13.7, 4.6 Hz, 1H),
3.40 (ddd, J=13.3, 6.8, 4.3 Hz, 1H), 4.75 (d, J=12.9 Hz,
1H), 4.86 (d, J=12.9 Hz, 1H), 7.56 (d, J=2.2 Hz, 1H), 8.28
(d, J=2.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=24.5,
25.0, 26.4, 26.5, 26.9, 27.8, 28.0, 28.3, 32.1, 33.5, 61.0, 134.8,
134.9, 135.5, 147.5, 156.8; CD (MeCN): lext =220 (De=
+26.0), 251 (À6.3), 276 (+16.6); [a]2D6: +81.7 (c 1.0, CHCl3).
HR-MS (EI, 70 eV): m/z=247.1904, calcd. for C16H25NO+
[M]+: 247.1936.
Synthesis of 3 and 4
The benzylisoxazolidinone derivatives 3 and 4 were ob-
tained according to the experimental protocol that we pub-
lished previously for the preparation of the corresponding
(S)-isopropyloxazolidinone derivatives.[15a]
A
CHCl3 (8 mL) solution of the alcohol (196 mg,
0.792 mmol) thus obtained was treated with thionyl chloride
(170 mL, 2.38 mmol), and the reaction mixture was stirred at
room temperature for 1 h. After concentration of the reac-
tion mixture under vacuum, the residue was dissolved in
ether and a saturated sodium bicarbonate solution was
added to give pHꢀ8. The ethereal layer was removed, the
aqueous layer was further extracted with ether, and the
combined ethereal layers were dried over MgSO4. After re-
moval of the solvent under vacuum, the residue was dis-
solved in THF (4 mL) and added to a mixture of LiAlH4
(45 mg, 1.18 mmol) in anhydrous THF (4 mL) at 08C; the
mixture was stirred at room temperature for 4 h. The stan-
dard procedure described above was used, and the residual
crude product was further purified by flash chromatography
1
3: oil; H NMR (399.78 MHz, CDCl3): d=0.47 (m, 1H),
0.58–0.65 (m, 2H), 0.72–0.91 (m, 5H), 1.01–1.17 (m, 2H),
1.20–1.30 (m, 2H), 1.45 (m, 1H), 1.56 (m, 1H), 1.74–1.87
(m, 2H), 2.60 (ddd, J=18.0, 10.0, 4.0 Hz, 1H), 2.73 (ddd,
J=18.0, 10.0, 4.8 Hz, 1H), 2.85 (dd, J=12.8, 10.0 Hz, 1H),
2.95 (t, J=5.6 Hz, 2H), 3.59 (dd, J=12.8, 5.6 Hz, 1H), 4.25
(dd, J=9.2, 4.4 Hz, 1H), 4.30 (t, J=9.2 Hz, 1H), 4.91 (ddd,
J=12.8, 7.6, 4.4 Hz, 1H) 7.28–7.39 (m, 5H), 7.52 (d, J=
2.0 Hz, 1H), 8.47 (d, J=2.0 Hz, 1H); 13C NMR (67.80 MHz,
CDCl3): d=24.6, 25.2, 26.3, 26.4, 27.6, 27.65, 27.70, 28.3,
31.9, 35.1, 37.9, 55.2, 66.3, 127.3, 128.8 (2C), 129.2 (2C),
129.4, 133.7, 134.8, 136.1, 150.5, 152.1, 157.3, 168.3; CD
2972
asc.wiley-vch.de
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2966 – 2978

Enantioselective Cyclopropanation Reactions with Planar-Chiral Pyridinium Ylides
(MeCN): lext =218 (De= +2.6), 238 (+12.4), 262 (+5.8),
280 (+9.5); HR-MS (FAB+): m/z=421.2479, calcd. for
6: colorless oil; 1H NMR (399.65 MHz, CDCl3): d=0.12
(s, 9H), 0.18 (m, 1H), 0.23 (m, 1H), 0.45 (m, 1H), 0.52 (m,
1H), 0.81 (m, 1H), 0.99–1.20, 1.33 (m, 1H), 1.40–1.66 (m,
4H), 1.92–2.09 (m, 2H), 2.77 (ddd, J=14.2, 9.9, 3.3 Hz, 1H),
2.95 (ddd, J=13.7, 5.2, 4.6 Hz, 1H), 3.03 (ddd, J=14.2, 6.3,
4.6 Hz, 1H), 3.57 (ddd, J=13.7, 10.3, 4.6 Hz, 1H), 7.41 (dd,
J=7.4, 2.9 Hz, 2H), 7.53–7.57 (m, 5H), 7.62 (t, J=7.4 Hz,
2H), 7.74 (d, J=7.4 Hz, 2H), 8.54 (d, J=1.7 Hz, 1H);
13C NMR (125.77 MHz, CDCl3): d=1.73 (3C), 24.7, 26.6,
26.8, 27.0, 27.1, 29.7 (2C), 30.3, 32.2, 34.5, 85.2, 127.0, 127.6,
127.69 (2C), 127.74 (2C), 128.4 (2C), 129.8 (2C), 132.2,
+
C26H33N2O3 [M+H]+: 421.2491.
4: oil; 1H NMR (399.78 MHz, CDCl3): d=0.44–0.51 (m,
1H), 0.57–0.67 (m, 2H), 0.80–0.88 (m, 5H), 1.09–1.15 (m,
2H), 1.22–1.29 (m, 2H), 1.42–1.50 (m, 1H), 1.59–1.66 (m,
1H), 1.76–1.89 (m, 2H), 2.63 (ddd, J=14.0, 10.0, 4.5 Hz,
1H), 2.75 (ddd, J=13.5, 6.0, 4.5 Hz, 1H), 2.83 (ddd, J=12.5,
8.0, 4.0 Hz, 1H), 2.93 (m, 1H), 2.95 (dd, J=10.0, 3.0 Hz,
1H), 3.52 (dd, J=13.0, 3.0 Hz, 1H), 4.26 (dd, J=9.0, 3.0 Hz,
1H), 4.33 (t, J=9.0 Hz, 1H), 4.85 (m, 1H) 7.27 (d, J=
7.0 Hz, 2H), 7.31 (t, J=7.0 Hz, 1H), 7.37 (t, J=7.0 Hz, 2H),
7.45 (d, J=2.3 Hz, 1H), 8.48 (d, J=2.3 Hz, 1H); 13C NMR
(125.77 MHz, CDCl3): d=24.5, 24.9, 26.2, 26.3, 27.4, 27.5,
27.6, 28.1, 31.8, 35.0, 37.4, 53.3, 55.5, 66.1, 127.3, 128.8 (2C),
129.2, 129.3 (2C), 133.6, 134.8, 135.7, 150.9, 152.2, 156.6,
168.3; CD (MeCN): lext =207 (De=À22.2), 210 (À21.6), 211
(À21.8), 241 (+9.8), 261 (+4.7), 280 (+7.9); HR-MS
137.1, 141.1, 144.4, 146.1, 146.9, 159.8; CD (MeCN): lext
=
206 (De= +50.7), 234 (+2.8), 238 (+3.5), 256 (À4.2), 282
(+18.8); [a]2D6: +59.0 (c 1.0 in CHCl3); HR-MS (FAB+):
m/z=472.3039, calcd. for C31H42NOSi+ [M+H]+: 472.3036.
7: colorless oil; 1H NMR (399.65 MHz, CDCl3): d=0.18
(s, 9H), 0.24 (m, 1H), 0.35 (m, 1H), 0.50 (m, 1H), 0.83 (t,
J=7.4 Hz, 6H), 0.86–1.02 (m, 5H), 1.10 (m, 1H), 1.14–1.36
(m, 11H), 1.56 (m, 1H), 1.74–1.86 (m, 5H), 1.92 (m, 1H),
2.17 (ddd, J=14.3, 12.6, 4.6 Hz, 1H), 2.50 (ddd, J=13.7,
10.9, 4.0 Hz, 1H), 2.73 (dt, J=13.7, 4.6 Hz, 1H), 2.79 (ddd,
J=13.7, 7.4, 4.6 Hz, 1H), 3.37 (ddd, J=13.7, 8.0, 4.6 Hz,
1H), 7.36 (d, J=1.7 Hz, 1H), 8.20 (d, J=1.7 Hz, 1H);
13C NMR (125.77 MHz, CDCl3): d=2.4 (3C), 14.07, 14.13,
22.8, 23.0, 25.2, 25.3, 25.8, 26.6, 26.7, 26.8, 27.95, 28.05, 28.1,
28.9, 32.4, 35.5, 42.3, 42.8, 81.5, 133.0, 135.8, 138.7, 146.5,
157.3; CD (MeCN): lext =280 (De=+9.3), 253 (À3.2), 222
(+10.6); [a]2D3: +36.3 (c 0.6 in CHCl3); HR-MS (FAB+):
m/z=431.3662, calcd. for C27H50NOSi+ [M+H]+: 432.3668.
+
(FAB+): m/z=421.2480, calcd. for C26H33N2O3 [M+H]+:
421.2491.
Synthesis of TMS Ethers 5–7: Representative
Procedure
To a solution of (S)-1 (206 mg, 0.748 mmol) in anhydrous
THF (8 mL) was added a butyllithium solution in hexane
(2.24 mmol) at À208C. After stirring the mixture at À208C
for 5 h, the solvent was removed under vacuum and a satu-
rated ammonium chloride solution was added to the mix-
ture. The aqueous layer was extracted with ether (3ꢁ) and
the combined ethereal solution was washed with brine and
dried over MgSO4. After concentration of the mixture
under vacuum, the residue was purified by flash chromatog-
raphy with ether/hexane (1/4) to give the desired tertiary al-
cohol 7; yield: 269 mg (0.748 mol, quantitative).
The compound (235 mg, 0.654 mmol) thus obtained was
dissolved in dichloromethane (7 mL) and imidazole
(113 mg, 1.96 mmol) and trimethylsilyl chloride (130 mL,
0.978 mmol) were added successively to the mixture at 08C.
After stirring the reaction mixture at room temperature for
19 h, water was added and the aqueous layer was extracted
with dichloromethane (3ꢁ). The combined organic layer
was washed with brine and was dried over MgSO4. After re-
moval of the solvent under vacuum, the resulting crude
product was purified by flash chromatography on silica gel
using ether/hexane (1/4), to give TMS ether 7; yield: 225 mg
(0.521 mmol, 80%).
Asymmetric Cyclopropanation Reactions with Planar-
Chiral Pyridinium Ylides: Representative Procedure
To a solution of the pyridinium bromide 14e (42 mg,
0.063 mmol) in anhydrous dichloromethane (0.60 mL) was
added triethylamine (13 mL, 0.095 mmol) at 08C, and the
mixture was stirred at 08C for 1 h. Benzalmalononitrile
(16q) (8.8 mg, 0.057 mmol) was added, and the reaction mix-
ture was stirred at room temperature for 2 h. After the reac-
tion was complete, the reaction was quenched with saturated
aqueous ammonium chloride solution and the aqueous
phase was extracted with dichloromethane (3ꢁ). The organ-
ic phase was dried over anhydrous MgSO4, and concentrated
under vacuum. The residue was then separated by TLC on
silica gel using ethyl acetate/cyclohexane (1/10) to give cy-
clopropane 17eq (yield: 13 mg, 0.048 mmol, 85%, 93% ee)
and pyridinophane 6 (yield: 23 mg, 0.048 mmol, 85%).
The enantiomeric excess of (À)-17eq was measured by
HPLC (DAICEL Chemical Industries, Ltd., CHIRALPAK
AD-H, 10% isopropyl alcohol in hexane). The enantiomeric
excess of (À)-17eq increased to 99% after recrystallization
from methanol. The absolute structure was identified as
(1R,3S)-17eq by X-ray crystallographic analysis. Chiral
HPLC analysis (DAICEL Chemical Industries, Ltd., CHIR-
ALPAK AD-H, 10% isopropyl alcohol in hexane, flow rate
1.0 mL/min): 10.8 min for (À)-(1R,3S)-17eq and 12.9 min for
(+)-(1S,3R)-17eq.
Similar experimental protocols were employed for the
syntheses of 5 and 6, using methyl- and phenyllithium, re-
spectively, instead of butyllithium.
5: colorless oil; 1H NMR (399.65 MHz, CDCl3): d=0.09
(s, 9H), 0.33–0.48 (m, 2H), 0.53 (m, 1H), 0.62–0.98 (m, 6H),
1.05–1.39 (m, 5H), 1.67 (s, 3H), 1.70 (s, 3H), 1.80 (m, 1H),
1.92 (m, 1H), 2.52 (ddd, J=13.3, 10.5, 4.1 Hz, 1H), 2.70 (dt,
J=13.3, 5.0 Hz, 1H), 2.87 (ddd, J=13.7, 6.4, 4.6 Hz, 1H),
3.48 (ddd, J=13.7, 9.2, 3.7 Hz, 1H), 7.40 (d, J=1.8 Hz, 1H),
8.24 (d, J=1.8 Hz, 1H); 13C NMR (125.77 MHz, CDCl3):
d=2.4 (3C), 25.3, 25.4, 26.5, 26.6, 27.6, 27.8 (2C), 28.4, 32.2,
32.3, 32.5, 35.0, 75.3, 133.29, 133.34, 142.0, 146.8, 157.8; CD
(MeCN): lext =278 (De=+16.5), 253 (À5.6), 220 (+19.6);
[a]1D8: +73.3 (c 1.0 in CHCl3); HR-MS (FAB+): m/z=
348.2720, calcd. for C21H38NOSi+ [M+H]+: 348.2723.
1
9a (R1 =Ph, R2 =Me): yellow oil; H NMR (399.65 MHz,
CDCl3): d=0.50 (m, 1H), 0.62 (m, 1H), 0.70–1.01 (m, 5H),
1.12 (m, 2H), 1.23 (m, 1H), 1.38 (m, 1H), 1.59–1.83 (m,
4H), 2.00 (m, 1H), 2.66 (s, 3H), 2.78 (m, 2H), 3.03–3.10 (m,
1H), 3.21 (ddd, J=15.2, 8.5, 5.4 Hz, 1H), 6.02 (d, J=
Adv. Synth. Catal. 2010, 352, 2966 – 2978
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2973

Nobuhiro Kanomata et al.
COMMUNICATIONS
18.5 Hz, 1H), 7.58 (t, J=7.8 Hz, 2H), 7.69 (t, J=7.8 Hz,
1H), 8.00 (s, 1H), 8.30 (d, J=7.8 Hz, 2H), 8.45 (d, J=
18.5 Hz, 1H), 9.96 (s, 1H); 13C NMR (125.77 MHz, CDCl3):
d=19.8, 24.07, 24.13, 25.5, 25.6, 25.9, 27.1, 27.3, 27.6, 28.2,
31.1, 64.1, 128.6 (2C), 128.8 (2C), 132.7, 134.6, 137.3, 140.0,
145.2, 147.0, 155.6, 189.2; CD (MeCN): lext =209 (De=
+19.0), 247 (À6.0), 279 (+0.9); [a]2D1: À83.5 (c 1 in CHCl3);
HR-MS (FAB+): m/z=350.2480, calcd. for C24H32NO+ [M]+:
d=20.2, 24.4, 24.6, 25.9, 26.0, 26.2, 27.5, 27.6, 27.9 (4C),
28.4, 31.5, 59.0, 85.4, 137.2, 140.5, 147.2 (2C), 154.7, 164.6;
CD (MeCN): lext =274 (De=+1.0), 239 (À2.3), 209
(+15.8); [a]2D6: +0.83 (c 1.0 in CHCl3); HR-MS (FAB+):
+
m/z=346.2752, calcd. for C22H36NO2 [M]+: 346.2746, m/z=
+
771.4641, calcd. for C44H7279BrN2O4 [2M+Br]+: 771.4675.
10a (R1 =Ph, R2 =CO2Me): yellow oil; 1H NMR
(399.65 MHz, CDCl3): d=0.32 (m, 1H), 0.57 (m, 1H), 0.78
(m, 2H), 0.95 (m, 3H), 1.09 (m, 2H), 1.24 (m, 2H), 1.37 (m,
1H), 1.61–1.75 (m, 3H), 2.03 (m, 1H), 2.70 (ddd, J=14.9,
7.1, 5.3 Hz, 1H), 2.84 (ddd, J=14.0, 9.0, 5.0 Hz, 1H), 3.14
(ddd, J=14.0, 9.0, 5.0 Hz, 1H), 4.08 (s, 3H), 4.14 (m, 1H),
6.20 (d, J=18.3 Hz, 1H), 7.59 (t, J=7.7 Hz, 2H), 7.70 (t, J=
7.7 Hz, 1H), 8.28 (d, J=8.4 Hz, 2H), 8.47 (d, J=18.3 Hz,
1H), 8.69 (s, 1H), 10.44 (s, 1H); 13C NMR (100.40 MHz,
CDCl3): d=24.3, 24.8, 25.9, 26.2, 27.2, 27.5, 27.7, 28.1, 29.1,
31.7, 54.0, 64.8, 129.2 (2C), 129.4 (2C), 130.7, 133.0, 135.3,
350.2478, m/z=779.4187, calcd. for C48H6479BrN2O2 [2M+
+
Br]+: 779.4151.
9b (R1 =MeO, R2 =Me): oil (foam); 1H NMR
(270.05 MHz, CDCl3): d=0.37 (m, 1H), 0.52–1.01 (m, 6H),
1.02–1.78 (m, 5H), 1.81–2.03 (m, 4H), 2.62 (s, 3H), 2.77
(ddd, J=13.8, 7.6, 4.8 Hz, 1H), 2.97 (dt, J=15.4, 5.8 Hz,
1H), 3.11 (ddd, J=13.8, 8.6, 4.5 Hz, 1H), 3.23 (ddd, J=15.4,
8.7, 5.3 Hz, 1H), 3.87 (s, 3H), 5.66 (d, J=17.6 Hz, 1H), 6.91
(d, J=17.6 Hz, 1H), 8.01 (s, 1H), 10.03 (s, 1H); 13C NMR
(125.40 MHz, CDCl3): d=20.2, 24.4, 24.6, 26.0 (2C), 26.2,
27.4, 27.6, 27.9, 28.5, 31.5, 53.8, 58.2, 137.5, 140.7, 146.9,
147.5, 155.0, 166.2; CD (MeCN): lext =296 (De=À0.68), 276
(+2.9), 239 (À5.2), 210 (+42.5), 208 (+38.3), 206 (+42.1),
203 (+18.3), 202 (+30.4); [a]2D3: +16.7 (c 0.3 in CHCl3);
141.2, 146.9, 151.1, 159.4, 163.5, 189.2; CD (MeCN): lext
=
231 (De= +8.2), 258 (+0.7), 271 (+1.1), 295 (À0.9); [a]2D1:
À53.7 (c 1 in CHCl3); HR-MS (FAB+): m/z=394.2385,
+
calcd. for C25H32NO3 [M]+: 394.2382.
10b (R1 =MeO, R2 =CO2Me): colorless oil (foam);
1H NMR (399.65 MHz, CDCl3): d=0.156 (m, 1H), 0.52 (m,
1H), 0.66–1.38 (m, 10H), 1.56–2.00 (m, 4H), 2.88 (ddd, J=
13.9, 8.2, 4.5 Hz, 1H), 3.01 (m, 1H), 3.21 (ddd, J=13.9, 7.8,
4.5 Hz, 1H), 3.89 (s, 3H), 4.07 (s, 3H), 4.13 (m, 1H), 5.91
(d, J=17.6 Hz, 1H), 6.88 (d, J=17.6 Hz, 1H), 8.69 (s, 1H),
10.43 (s, 1H); 13C NMR (100.40 MHz, CDCl3): d =23.9,
24.8, 25.8, 26.0, 27.0, 27.2, 27.4, 28.0, 28.9, 31.3, 53.9, 54.0,
58.3, 131.0, 141.1, 147.1, 151.3, 158.5, 163.3, 165.8; CD
(MeCN): lext =296 (De=À0.264), 276 (+1.59), 228 (+10.6),
202 (À6.8); [a]2D1: +38.0 (c 1.0 in CHCl3); HR-MS (FAB+):
+
HR-MS (FAB+): m/z=304.2278, calcd. for C19H30NO2
[M]+: 304.2277, m/z=687.3725, calcd. for C38H6079BrN2O4
+
[2M+Br]+: 687.3736.
9c (R1 =EtO, R2 =Me): yellow oil (foam); 1H NMR
(270.05 MHz, CDCl3): d=0.38 (m, 1H), 0.52–1.01 (m, 6H),
1.02–1.56 (m, 5H), 1.36 (t, J=7.0 Hz, 3H), 1.69 (m, 2H),
1.90 (m, 2H), 2.62 (s, 3H), 2.76 (ddd, J=13.5, 8.0, 5.0 Hz,
1H), 2.94 (ddd, J=15.2, 7.0, 5.1 Hz, 1H), 3.12 (ddd, J=13.5,
8.0, 5.0 Hz, 1H), 3.22 (ddd, J=15.2, 9.1, 5.1 Hz, 1H), 4.31
(m, 2H), 5.62 (d, J=17.7 Hz, 1H), 6.84 (d, J=17.7 Hz, 1H),
7.99 (s, 1H), 10.04 (s, 1H); 13C NMR (100.40 MHz, CDCl3):
d=14.0, 20.2, 24.4, 24.6, 25.9, 26.2, 27.4, 27.6, 27.9, 28.4,
31.5, 58.3, 63.4, 77.2, 137.3, 140.7, 147.1, 147.4, 154.8, 165.8;
CD (MeCN): lext =276 (De=+2.2), 239 (À2.5), 210
(+20.4); [a]2D3: +8.5 (c 1.0 in CHCl3); HR-MS (FAB+): m/
+
m/z=348.2173, calcd. for C20H30NO4 [M]+: 348.2169, m/z=
+
775.3543, calcd. for C40H60N2O8 [2M+Br]+: 775.3533.
10e (R1 =t-BuO, R2 =CO2Me): oil (foam); 1H NMR
(399.65 MHz, CDCl3): d=0.18 (m, 1H), 0.53 (m, 1H), 0.69–
0.96 (m, 5H), 0.98–1.22 (m, 2H), 1.31 (m, 1H), 1.53 (s, 9H),
1.67 (m, 1H), 1.72–1.90 (m, 4H), 1.96 (m, 1H), 2.80–2.90
(m, 2H), 3.25 (ddd, J=13.9, 8.3, 4.6 Hz, 1H), 4.05 (s, 3H),
4.15 (ddd, J=15.4, 8.8, 4.6 Hz, 1H), 5.72 (d, J=17.3 Hz,
1H), 6.59 (d, J=17.3 Hz, 1H), 8.63 (d, J=1.7 Hz, 1H),
10.38 (d, J=1.7 Hz, 1H); 13C NMR (100.40 MHz, CDCl3): d
=24.1, 24.9, 25.9, 26.1, 27.1, 27.4, 27.5, 27.9 (3C), 28.1, 28.8,
31.5, 54.0, 59.2, 85.9, 130.7, 141.0, 146.9, 151.9, 158.1, 163.5,
164.2; CD (MeCN): lext =295 (De=À1.9), 227 (+16.2), 203
(À6.9); [a]2D1: +28.9 (c 1.0 in CHCl3). HR-MS (FAB+):
+
z=318.2442, calcd. for C20H32NO2 [M]+: 318.2433, m/z=
715.4048, calcd. for C40H6479BrN2O4 [2M+Br]+: 715.4049.
+
9d (R1 =BnO, R2 =Me): oil (foam); 1H NMR
(270.05 MHz, CDCl3): d=0.31 (m, 1H), 0.54 (m, 1H), 0.69–
1.38 (m, 9H), 1.49–2.01 (m, 5H), 2.59 (s, 3H), 2.76 (ddd, J=
13.8, 7.7, 4.6 Hz, 1H), 2.89 (ddd, J=15.3, 6.4, 5.6 Hz, 1H),
3.04–3.21 (m, 2H), 5.27 (s, 2H), 5.70 (d, J=17.6 Hz, 1H),
6.82 (d, J=17.6 Hz, 1H), 7.32–7.41 (m, 5H), 7.99 (s, 1H),
9.99 (s, 1H); 13C NMR (100.40 MHz, CDCl3): d =20.2, 24.3,
24.6, 25.9, 26.0, 26.2, 27.4, 27.6, 27.9, 28.4, 31.6, 58.3, 68.9,
128.7 (2C), 128.8 (2C), 128.9, 134.2, 137.3, 140.7, 147.1,
147.3, 154.8, 165.7; CD (MeCN): lext =276 (De=+1.2), 239
(À2.7), 209 (+19.7); [a]23: +5.8 (c 1.0 in CHCl3); HR-MS
+
m/z=390.2647, calcd. for C23H36NO4 [M]+: 390.2644, m/z=
+
859.4475, calcd. for C46H72N2O8 [2M+Br]+: 859.4472.
11a
[R1 =Ph,
R2 =CO-(S)-BnOx]:
oil;
1H NMR
(FAB+): m/z=380.2584D, calcd. for C25H34NO2 [M]+:
+
(270.05 MHz, CDCl3): d=0.08 (m, 1H), 0.66–1.37 (m, 10H),
1.49 (m, 1H), 1.80–1.92 (m, 4H), 2.79 (ddd, J=18.9, 6.8,
5.1 Hz, 1H), 2,90–3.10 (m, 4H), 3.46 (dd, J=13.2, 3.2 Hz,
1H), 4.30 (dd, J=8.9, 2.4 Hz, 1H), 4.58 (t, J=8.9 Hz 1H),
4.95–5.10 (m, 1H), 6.27 (d, J=17.8 Hz, 1H), 7.25–7.38 (m,
5H), 7.54 (t, J=7.0 Hz, 2H), 7.67 (t, J=7.0 Hz, 1H), 7.87
(d, J=17.8 Hz, 1H), 8.24 (d, J=7.0 Hz, 2H), 8.40 (s, 1H),
9.88 (s, 1H); 13C NMR (67.80 MHz, CDCl3): d=24.1, 24.9,
26.2, 26.4, 27.1, 27.2, 27.6, 28.0, 30.6, 31.4, 37.9, 55.5, 63.6,
67.5, 127.4, 128.9 (4C), 129.1 (2C), 129.3 (2C), 133.1, 134.5,
134.8, 135.4, 140.3, 145.2, 148.8, 152.6, 154.8, 163.7, 188.7;
380.2590, m/z 839.4356, calcd. for C50H6879BrN2O4 [2M+
+
Br]+: 839.4362.
9e (R1 =t-BuO, R2 =Me): colorless oil; 1H NMR
(500.00 MHz, CDCl3): d=0.36 (m, 1H), 060 (m, 1H), 0.69–
0.86 (m, 4H), 0.86–0.98 (m, 2H), 1.04 (m, 1H), 1.08–1.19
(m, 2H), 1.31 (m, 1H), 1.52 (s, 9H), 1.62–1.73 (m, 2H),
1.83–1.99 (m, 2H), 2.61 (s, 3H), 2.75 (ddd, J=13.9, 7.6,
4.6 Hz, 1H), 2.91 (ddd, J=15.3, 6.8, 5.3 Hz, 1H), 3.12 (ddd,
J=13.9, 8.2, 4.3 Hz, 1H), 3.22 (ddd, J=15.3, 8.9, 5.2 Hz,
1H), 5.51 (d, J=17.4 Hz, 1H), 6.63 (d, J=17.4 Hz, 1H),
7.95 (s, 1H), 9.99 (s, 1H); 13C NMR (100.40 MHz, CDCl3):
+
HR-MS (FAB+): m/z=539.2894, calcd. for C34H39N2O4
2974
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2966 – 2978

Enantioselective Cyclopropanation Reactions with Planar-Chiral Pyridinium Ylides
[M]+: 539.2910; HR-MS (ESI+): m/z=1157.5018, calcd. for
4.1 Hz, 1H), 2.77 (dt, J=16.1, 4.9 Hz, 1H), 3.08 (ddd, J=
+
C68H7879BrN4O8 [2M+Br]+: 1157.5003.
13.9, 9.8, 4.1 Hz, 1H), 3.83 (s, 3H), 4.00 (ddd, J=16.1, 10.7,
5.4 Hz, 1H), 5.67 (d, J=17.6 Hz, 1H), 6.76 (d, J=17.6 Hz,
1H), 7.04 (dd, J=7.7, 1.8 Hz, 2H), 7.46–7.33 (m, 8H), 7.91
(s, 1H), 10.07 (s, 1H); 13C NMR (100.40 MHz, CDCl3): d=
1.7 (3C), 24.1, 25.1, 25.9, 26.5, 27.3, 27.4, 27.6, 28.0, 29.3,
31.5, 53.7, 58.1, 85.5, 127.9 (2C), 128.4, 128.6 (2C), 128.8
(2C), 129.0, 129.7 (2C), 139.1, 141.6, 143.8, 145.2, 147.7,
149.0, 158.2, 166.2; CD (MeCN): lext =286 (De=+2.7), 255
(À2.4), 218 (+23.3), 210 (+19.0), 207 (+19.9), 204 (+19.3),
203 (+19.8), 201 (+18.8); [a]2D8: +70.8 (c 1.0 in CHCl3);
HR-MS (FAB+): m/z=544.3233, calcd. for C34H46NO3Si+
12a [R1 =Ph, R2 =CO-(R)-BnOx]: yellow solid; mp 119.9–
1
124.38C; H NMR (399.65 MHz, CDCl3): d=0.14 (m, 1H),
0.72–0.86 (m, 2H), 0.88–1.00 (m, 2H), 1.02–1.12 (m, 3H),
1.15–1.28 (m, 3H), 1.40 (m, 1H), 1.67 (m, 1H), 1.77 (m,
1H), 1.90 (m, 1H), 2.01 (m, 1H), 2.80 (ddd, J=13.9, 7.9,
4.8 Hz, 1H), 2.99 (m, 2H), 3.04–3.16 (m, 3H), 3.49 (dd, J=
13.3, 3.1 Hz, 1H), 4.51 (t, J=8.5, Hz, 1H), 4.94 (m, 1H),
6.08 (d, J=18.1 Hz, 1H), 7.28 (m, 2H) 7.34 (t, J=7.4 Hz,
1H), 7.39 (t, J=7.4 Hz, 2H), 7.56 (t, J=7.6 Hz, 2H), 7.67 (t,
J=7.6 Hz, 1H), 7.96 (s, 1H), 8.28 (d, J=7.6 Hz, 2H), 8.38
(d, J=18.1 Hz, 1H), 10.13 (s, 1H); 13C NMR (125.77 MHz,
CDCl3): d=24.4, 24.8, 26.2, 26.4, 27.3, 27.4, 27.5, 28.0, 30.6,
31.6, 37.4, 55.5, 64.3, 67.4, 127.7, 129.1 (2C), 129.18 (2C),
129.23 (2C), 129.5 (2C), 133.1, 134.4, 134.7, 135.1, 140.6,
144.4, 149.6, 152.4, 155.2, 163.7, 188.9; HR-MS (FAB+):
[M]+: 544.3241, m/z=167.5682, calcd. for C68H9279BrN2O6Si2
+
[2M+Br]+: 1167.5677.
14c (R1 =EtO, R2 =CPh2OTMS): oil (foam); 1H NMR
(399.65 MHz, CDCl3): d=À0.47 (m, 1H), À0.37 (m, 1H),
À0.18 (s, 9H), 0.25–0.40 (m, 2H), 0.42 (m, 1H), 0.56 (m,
1H), 0.76–0.90 (m, 4H), 1.02 (m, 1H), 1.15–1.29 (m, 2H),
1.29 (d, J=7.2 Hz, 3H), 1.38–1.56 (m, 2H), 1.85 (m, 1H),
2.63–2.78 (m, 2H), 3.05 (ddd, J=13.9, 9.5, 3.9 Hz, 1H), 3.97
(ddd, J=15.9, 11.2, 5.4 Hz, 1H), 4.25 (q, J=7.2 Hz, 2H),
5.62 (d, J=17.6 Hz, 1H), 6.66 (d, J=17.6 Hz, 1H), 7.02 (dd,
J=7.6, 1.7 Hz, 2H), 7.29–7.43 (m, 8H), 7.89 (s, 1H); 10.05
(s, 1H); 13C NMR (100.40 MHz, CDCl3): d=1.6 (3C), 14.0,
24.0, 25.0, 25.9, 26.4, 27.2, 27.3, 27.5, 27.8, 29.2, 31.4, 58.1,
63.2, 85.4, 127.8 (2C), 128.3, 128.5 (2C), 128.7 (2C), 129.0,
129.6 (2C), 138.9, 141.5, 143.8, 145.1, 147.6, 148.8, 158.0,
165.6; CD (MeCN): lext =290 (De=+2.4), 255 (À2.4), 218
(+18.3), 211 (+14.3); [a]25: +48.4 (c 1.0 in CHCl3); HR-MS
(FAB+): m/z=558.3430,D calcd. for C35H48NO3Si+ [M]+:
+
m/z=539.2930, calcd. for C34H39N2O4 [M]+: 539.2910; HR-
MS (ESI+): m/z=1157.4993, calcd. for C68H7879BrN4O8
+
[2M+Br]+: 1157.5003.
13a (R1 =Ph, R2 =CMe2OTMS): yellow solid; mp 107.9–
111.18C; 1H NMR (399.78 MHz, CDCl3): d=0.18 (s, 9H),
0.68–1.00 (m, 9H), 1.11–1.33 (m, 4H), 1.66–1.69 (m, 2H),
1.73 (s, 3H), 1.83 (s, 3H), 1.91 (m, 1H), 2.68 (dt, J=15.1,
5.0 Hz, 1H), 2.80 (ddd, J=13.7, 7.3, 4.1 Hz, 1H), 2.99 (ddd,
J=13.7, 6.2, 4.1 Hz, 1H), 4.12 (ddd, J=15.1, 10.1, 6.0 Hz,
1H), 6.07 (d, J=18.3 Hz, 1H), 7.52 (t, J=7.6 Hz, 2H), 7.63
(t, J=7.6 Hz, 1H), 8.13 (s, 1H), 8.23 (d, J=7.6 Hz, 2H),
8.24 (d, J=18.3 Hz, 1H), 9.87 (s, 1H); 13C NMR
(125.77 MHz, CDCl3): d=2.4 (3C), 24.80, 24.83, 25.9, 26.5,
27.1, 27.3, 27.4, 27.9, 28.8, 31.6, 32.1, 32.9, 64.8, 75.8, 129.0
(2C), 129.1 (2C), 133.2, 134.8, 139.8, 142.0, 146.3, 148.0,
157.4, 189.6; CD (MeCN): lext =281 (De=+0.03), 252
(À0.06), 208 (+0.1), 204 (+0.06), 202 (+0.1); HR-MS
(FAB+): m/z=466.3144, calcd. for C29H44NO2Si+ [M]+:
558.3403, m/z=1195.5952, calcd. for C70H9679BrN2O6Si2
+
[2M+Br]+: 1195.5990.
14d (R1 =BnO, R2 =CPh2OTMS): oil (foam); 1H NMR
(399.65 MHz, CDCl3): d=À0.51 (m, 1H), À0.43 (m, 1H),
À0.17 (s, 9H), 0.20–0.38 (m, 2H), 0.42 (m, 1H), 0.58 (m,
1H), 0.73–0.83 (m, 4H), 1.04 (m, 1H), 1.12–1.32 (m, 2H),
1.39 (m, 1H), 1.54 (m, 1H), 1.87 (m, 1H), 2.63–2.77 (m,
2H), 3.08 (ddd, J=14.1, 9.5, 3.7 Hz, 1H), 3.95 (ddd, J=16.1,
11.2, 5.4 Hz, 1H), 5.20 (d, J=12.0 Hz, 1H), 5.31 (d, J=
12.0 Hz, 1H), 5.73 (d, J=17.6 Hz, 1H), 6.76 (d, J=17.6 Hz,
1H), 7.02 (d J=8.0 Hz, 2H), 7.28–7.46 (m, 13H), 7.89 (s,
1H), 10.11 (s, 1H); 13C NMR (100.40 MHz, CDCl3): d =1.65
(3C), 24.0, 25.1, 25.9, 26.5, 27.2, 27.3, 27.6, 27.9, 29.3, 31.5,
58.2, 68.8, 85.5, 127.8 (2C), 128.4, 128.60 (2C), 128.63 (2C),
128.7 (3C), 128.8 (2C), 129.1, 129.7 (2C), 134.4, 139.0, 141.6,
466.3141, m/z=1011.5496, calcd. for C58H8879BrN2O4Si2
+
[2M+Br]+: 1011.5466.
14a (R1 =Ph, R2 =CPh2OTMS): yellow solid; mp 101.1–
103.48C; H NMR (399.78 MHz, CDCl3): d=À0.36 (m, 1H),
1
À0.21 (m, 1H), À0.13 (s, 9H), 0.37–0.53 (m, 3H), 0.62 (m,
1H), 0.80–1.00 (m, 4H), 1.08 (m, 1H), 1.20–1.38 (m, 4H),
1.53 (m, 1H), 1.89 (m, 1H), 2.58 (ddd, J=16.0, 4.8, 4.5 Hz,
1H), 2.69 (ddd, J=13.7, 6.9, 4.2 Hz, 1H), 2.98 (ddd, J=13.7,
9.6, 3.7 Hz, 1H), 3.94 (ddd, J=16.0, 8.2, 7.8 Hz, 1H), 6.03
(d, J=18.3 Hz, 1H), 7.06–7.12 (m, 2H), 7.34–7.40 (m, 4H),
7.40–7.47 (m, 4H), 7.52 (t, J=7.6 Hz, 2H), 7.63 (t, J=
7.6 Hz, 1H), 7.94 (s, 1H), 8.23 (d, J=7.6 Hz, 2H), 8.27 (d,
J=18.3 Hz, 1H), 9.91 (s, 1H); 13C NMR (100.40 MHz,
CDCl3): d=1.67 (3C), 24.1, 25.2, 26.0, 26.6, 27.3, 27.5, 28.0,
29.4, 31.6, 64.8, 85.5, 127.9 (2C), 128.4, 128.5 (2C), 128.8
(2C), 129.0, 129.2 (2C), 129.7 (2C), 133.4, 134.8, 138.9,
141.8, 144.1, 144.9, 146.9, 148.7, 159.2, 189.6; CD (MeCN):
lext =291 (De=+0.02), 254 (À0.07), 220 (+0.2), 212 (+0.1),
209 (+0.2), 205 (+0.02), 204 (+0.08); HR-MS (FAB+):
m/z=590.3447, calcd. for C39H48NO2Si+ [M]+: 590.3454,
143.9, 145.2, 147.8, 149.0, 158.1, 165.8; CD (MeCN): lext
=
289 (De=+2.6), 254 (À3.2), 218 (+22.6), 211 (+15.0), 209
(+18.4), 207 (+14.1), 205 (+18.1), 203 (+11.6), 201
(+30.1); [a]2D8: +50.9 (c 1.0 in CHCl3); HR-MS (FAB+):
m/z=620.3579, calcd. for C40H50NO3Si+ [M]+: 620.3560,
m/z=1319.6284, calcd. for C80H10079BrN2O6Si2 [2M+Br]+:
+
1319.6303.
1
14e (R1 =t-BuO, R2 =CPh2OTMS): oil (foam); H NMR
(399.65 MHz, CDCl3): d =À0.38 (m, 2H), À0.15 (s, 9H),
0.26–0.38 (m, 2H), 0.44 (m, 1H), 0.60 (m, 1H), 0.76–0.97
(m, 4H), 1.04 (m, 1H), 1.16–1.36 (m, 3H), 1.43 (m, 1H),
1.49 (s, 9H), 1.88 (m, 1H), 2.63–2.78 (m, 2H), 3.09 (ddd, J=
13.7, 9.5, 3.9 Hz, 1H), 3.97 (ddd, J=15.9, 11.0, 5.1 Hz, 1H),
5.51 (d, J=17.6 Hz, 1H), 6.56 (d, J=17.6 Hz, 1H), 7.01–7.10
(m, 2H), 7.32–7.50 (m, 8H), 7.90 (s, 1H), 10.08 (s, 1H);
13C NMR (100.40 MHz, CDCl3): d=1.6 (3C), 24.0, 25.1,
26.0, 26.5, 27.2, 27.4, 27.7, 27.9 (4C), 29.3, 31.5, 59.0, 85.0,
+
m/z=1259.6102, calcd. for C78H9679BrN2O4Si2 [2M+Br]+:
1259.6092.
14b (R1 =MeO, R2 =CPh2OTMS): white crystal; 111.2–
1
112.88C; H NMR (399.65 MHz, CDCl3): d=À0.44 (m, 1H),
À0.34 (m, 1H), À0.15 (s, 9H), 0.26–0.49 (m, 3H), 0.59 (m,
1H), 0.78–0.93 (m, 4H), 1.05 (m, 1H), 1.17–1.32 (m, 2H),
1.42–1.60 (m, 2H), 1.85 (m, 1H), 2.71 (ddd, J=13.9, 7.1,
Adv. Synth. Catal. 2010, 352, 2966 – 2978
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asc.wiley-vch.de
2975

Nobuhiro Kanomata et al.
COMMUNICATIONS
85.4, 127.8 (2C), 128.4, 128.6 (2C), 128.7 (2C), 129.0, 129.7
(2C), 138.9, 141.7, 143.9, 144.9, 148.0, 148.7, 158.0, 164.7;
CD (MeCN): lext =299 (De=+4.1), 242 (À6.5), 219 (+43.3),
211 (+26.1); [a]1D6: +59.9 (c 1.0 in CHCl3); HR-MS (FAB+):
m/z=586.3716, calcd. for C37H52NO3Si+ [M]+: 586.3716,
(MeCN): lext =257 (De=+2.42), 226 (À0.79), 217 (+4.57);
[a]22: À107.3 (c 0.851 in CHCl3).
(DÀ)-(1R,3S)-17bq: 81% ee;[22a] white solid; 1H NMR
(399.65 MHz, CDCl3): d=3.16 (d, J=8.3 Hz, 1H), 3.70 (d,
J=8.3 Hz, 1H), 3.93 (s, 3H), 7.29–7.33 (m, 2H), 7.42–7.46
(m, 3H); CD (MeCN): lext =272 (De=+0.349), 269
(+0.213), 266 (+0.363), 263 (+0.200), 259 (+0.306), 256
(+0.151), 235 (À0.915), 219 (+1.52); [a]2D5: À108.6 (c 1.0 in
CHCl3).
m/z=1251.6605, calcd. for C74H10479BrN2O6Si2 [2M+Br]+:
+
1251.6616.
15a (R1 =Ph, R2 =CBu2OTMS): yellow solid; mp 102.1–
105.68C; 1H NMR (399.78 MHz, CDCl3): d=0.27 (s, 9H),
0.58 (m, 1H), 0.66 (m, 1H), 0.82 (m, 1H), 0.89 (t, J=7.2 Hz,
3H), 0.94 (t, J=7.2 Hz, 3H), 0.98 (m, 1H), 1.03–1.14 (m,
5H), 1.14–1.31 (m, 5H), 1.31–1.51 (m, 4H), 1.58 (m, 1H),
1.62–1.80 (m, 5H), 1.88 (ddd, J=14.9, 12.6, 3.4 Hz, 1H),
1.95–2.07 (m, 2H), 2.32 (ddd, J=14.9, 12.6, 4.0 Hz, 1H),
2.57 (ddd, J=14.9, 6.3, 5.7 Hz, 1H), 2.80 (ddd, J=13.7, 6.9,
4.6 Hz, 1H), 3.06 (ddd, J=14.3, 9.2, 4.0 Hz, 1H), 4.08 (dt,
J=14.9, 6.9 Hz, 1H), 6.04 (d, J=18.3 Hz, 1H), 7.56 (t, J=
7.5 Hz, 2H), 7.66 (t, J=7.5 Hz, 1H), 7.96 (s, 1H), 8.27 (d,
J=7.5 Hz, 2H), 8.44 (d, J=18.3 Hz, 1H), 10.04 (s, 1H).
13C NMR (125.77 MHz, CDCl3): d=2.4 (3C), 14.0, 14.1,
22.6, 22.9, 24.67, 24.72, 25.7, 26.0, 26.5, 26.6, 27.6, 27.9, 28.5,
28.6, 28.8, 31.8, 42.0, 45.2, 65.3, 82.9, 129.1 (2C), 129.2 (2C),
133.3, 134.9, 139.5, 144.5, 144.6, 146.4, 157.5, 189.5; CD
(MeCN): lext =282 (De=+0.02), 251 (À0.07), 207 (+0.2),
201 (À0.003); HR-MS (FAB+): m/z=550.4107, calcd. for
C35H56NO2Si+ [M]+: 550.4080, m/z=1179.7347, calcd. for
(À)-(1R,3S)-17cq: 79% ee; yellow oil; 1H NMR
(399.65 MHz, CDCl3): d=1.39 (t, J=7.2 Hz, 3H), 3.14 (d,
J=8.2 Hz, 1H), 3.62 (d, J=8.2 Hz, 1H), 4.37 (q, J=7.1 Hz,
2H), 7.29–7.33 (m, 2H), 7.42–7.46 (m, 3H); 13C NMR
(100.40 MHz, CDCl3): d=13.9, 14.1, 33.5, 38.4, 63.4, 111.6,
111.7, 128.2 (2C), 128.9, 129.3 (2C), 129.9, 164.9; CD
(MeCN): lext =273 (De=+0.397), 269 (+0.277), 266
(+0.480), 263 (+0.268), 259 (+0.403), 257 (+0.238), 234
(À1.08), 219 (+1.47), 201 (À6.10); [a]2D5: À105.0 (c 1.0 in
CHCl3); HR-MS (FAB+): m/z=241.0980, calcd. for
+
C14H13N2O2 [M+H]+: 241.0977.
(À)-(1R,3S)-17dq: 77% ee; colorless oil; 1H NMR
(399.65 MHz, CDCl3): d=3.17 (d, J=8.0 Hz, 1H), 3.69 (d,
J=8.0 Hz, 1H), 5.31 (s, 2H), 7.24–7.30 (m, 2H), 7.38–7.44
(m, 8H); 13C NMR (100.40 MHz, CDCl3): d=14.0, 33.4,
38.5, 69.0, 111.50, 111.52, 128.2 (2C), 128.75, 128.81 (2C),
129.0 (2C), 129.1, 129.3 (2C), 129.9, 134.0, 164.9; CD
(MeCN): lext =273 (De=+0.479), 269 (+0.277), 265
(+0.530), 263 (+0.335), 259 (+0.491), 235 (À0.252), 215
(+1.76), 201 (À4.52); [a]2D5: À68.9 (c 1.0 in CHCl3); HR-MS
C70H11279BrN2O4Si2 [2M+Br]+: 1179.7344.
+
15e (R1 =t-BuO, R2 =CBu2OTMS): oil (foam); mp 86–
1
938C (from ethyl acetate); H NMR (399.65 MHz, CDCl3):
+
d=0.12 (m, 1H), 0.20 (s, 9H), 0.43–0.62 (m, 2H), 0.73–1.58
(m, 25H), 1.44 (s, 9H), 1.60–2.08 (m, 5H), 2.23 (m, 1H),
2.65 (ddd, J=14.6, 8.5, 5.9 Hz, 1H), 2.76 (ddd, J=14.6, 6.6,
4.4 Hz, 1H), 3.06 (ddd, J=13.4, 9.5, 4.4 Hz, 1H), 4.05 (m,
1H), 5.36 (dd, J=17.6, 2.7 Hz, 1H), 6.71 (dd, J=17.6,
4.1 Hz, 1H), 7.92 (s, 1H), 10.12 (d, J=5.6 Hz, 1H);
13C NMR (100.40 MHz, CDCl3): d=2.2 (3C), 13.7, 13.8,
22.4, 22.6 24.6 (2C), 25.4, 25.9, 26.40, 26.44, 27.5, 27.8 (4C),
28.2, 28.32, 28.34, 31.5, 42.1, 44.5, 59.5, 82.7, 84.9, 139.6,
144.6, 144.8, 147.2, 156.1, 164.5; CD (MeCN): lext =280
(De=+1.2), 245 (À1.2), 210 (+7.5); [a]2D4: +4.69 (c 1 in
CHCl3); HR-MS (FAB): m/z=546.4340, calcd. for
C33H60NO3Si+ [M]+: 546.4342.
(FAB+): m/z=303.1128, calcd. for C19H15N2O2 [M+H]+:
303.1134.
(À)-(1R,3S)-17eq: >99% ee; white solid; mp 117.4–
1
117.88C (from MeOH); H NMR (399.65 MHz, CDCl3): d=
1.57 (s, 9H), 3.05 (d, J=8.3 Hz, 1H), 3.62 (d, J=8.3 Hz,
1H), 7.28–7.34 (m, 2H), 7.42–7.46 (m, 3H); 13C NMR
(100.40 MHz, CDCl3): d=13.6, 27.9 (3C), 34.5, 38.2, 85.2,
111.7, 111.9, 128.3 (2C), 129.1, 129.3 (2C), 129.8, 163.6; CD
(MeCN): lext =273 (De=+0.423), 269 (+0.192), 266
(+0.501), 263 (+0.204), 259 (+0.328), 256 (+0.0117), 233
(À2.49), 217 (+1.56), 201 (À11.4); À120.4 (c 1.0 in CHCl3);
+
HR-MS (FAB+): m/z=269.1304 calcd. for C16H17N2O2
[M+H]+: 269.1290.
(À)-(2R,3S)-17aq: 76% ee;[21] yellow oil; 1H NMR
(270.05 MHz, CDCl3): d=3.90 (d, J=8.4 Hz, 1H), 4.06 (d,
J=8.4 Hz, 1H), 7.37 (m, 2H), 7.45 (m, 3H), 7.59 (t, J=
7.6 Hz, 2H), 7.73 (t, J=7.6 Hz, 1H), 8.10 (d, J=7.3 Hz,
2H); 13C NMR (67.80 MHz, CDCl3): d=15.3, 35.5, 38.7,
111.5, 112.1, 128.2 (2C), 128.6 (2C), 129.1 (2C), 129.1 (2C),
129.3, 129.7, 134.9, 135.2, 188.6; CD (MeCN): lext =259
(De=+2.20), 219 (À1.52), 213 (+1.21); [a]2D4: À93.9 (c 0.687
in CHCl3); HR-MS (FAB+): m/z=273.1027, calcd. for
C18H13N2O+ [M+H]+: 273.1028; Chiral HPLC analysis
[CHIRALCEL OD, IPA-hexane (1/5), flow rate=
1.4 mL/min, 208C]: retention times: 10.4 min (+), 17.0 min
(À).
(À)-(1R,3S)-17es: 86% ee; yellow oil; 1H NMR
(399.65 MHz, CDCl3): d=1.55 (s, 9H), 3.17 (d, J=8.0 Hz,
1H), 3.61 (d, J=8.0 Hz, 1H), 6.43 (m, 1H), 6.52 (m, 1H),
7.45 (s, 1H); 13C NMR (100.40 MHz, CDCl3): d=12.9, 27.9
(3C), 31.8, 34.0, 85.4, 111.2, 111.3, 111.7, 111.8, 143.1, 144.2,
163.0; CD (MeCN): lext =249 (De=À2.7), 228 (À0.028), 202
(À5.0); [a]2D5: À148.8 (c 0.93 in CHCl3); HR-MS (FAB+):
+
m/z=259.1076, calcd. for C14H15N2O3 [M+H]+: 259.1083.
(À)-(1R,3S)-17et: 90% ee; yellow oil; 1H NMR
(399.65 MHz, CDCl3): d=1.56 (s, 9H), 3.01 (d, J=7.9 Hz,
1H), 3.74 (d, J=7.9 Hz, 1H), 7.04–7.09 (m, 2H), 7.38 (m,
1H); 13C NMR (100.40 MHz, CDCl3): d=14.6, 27.9 (3C),
33.6, 36.1, 85.4, 111.3, 111.7, 127.6 (2C), 128.2, 131.5, 163.0;
CD (MeCN): lext =248 (De=+6.0); [a]2D2: À98.0 (c 1.0 in
CHCl3); HR-MS (FAB+): m/z=275.0849, calcd. for
C14H15N2O2S+ [M+H]+: 275.0854.
(À)-(2R,3S)-17ar: 98% ee;[14,21b] white solid; mp 51.1–
52.08C (from column chromatography, 96% ee); 1H NMR
(500.16 MHz, CDCl3): d=1.21 (s, 9H), 2.57 (d, J=8.6 Hz,
1H), 3.59 (d, J=8.6 Hz, 1H), 7.59 (t, J=7.4 Hz, 2H), 7.72
(t, J=7.4 Hz, 1H), 8.06 (d, J=7.4 Hz, 2H); 13C NMR
(125.77 MHz, CDCl3): d=10.3, 28.2 (3C), 30.6, 34.8, 45.4,
112.2, 113.3, 128.6 (2C), 129.3 (2C), 134.9, 135.4, 189.3; CD
(À)-(1R,3S)-17eu: 90% ee; yellow oil; 1H NMR
(399.65 MHz, CDCl3): d=1.56 (s, 9H), 3.01 (d, J=8.0 Hz,
1H), 3.59 (d, J=8.0 Hz, 1H), 7.23–7.29 (m, 2H), 7.38–7.44
(m, 2H); 13C NMR (100.40 MHz, CDCl3): d=13.6, 27.9
2976
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2966 – 2978

Enantioselective Cyclopropanation Reactions with Planar-Chiral Pyridinium Ylides
(3C), 34.6, 37.4, 85.4, 111.4, 111.7, 127.6, 129.5 (2C), 129.6
(2C), 136.0, 163.3; CD (MeCN): lext =240 (De=À1.4), 219
(+3.2), 204 (À1.7); [a]1D9: À59.9 (c 1.0 in CHCl3); HR-MS
action was complete, toluene was added and the excess
formic acid was removed azeotropically under vacuum. The
residue was chromatographed on silica gel with ethyl ace-
tate/hexane (1/1) and then methanol/ethyl acetate (1/4) to
give the acid amide 18; yield: 289 mg (1.25 mmol, 86%);
white solid; mp 137.1–138.38C (from toluene); 1H NMR
(399.65 MHz, acetone-d6): d=3.35 (d, J=8.3 Hz, 1H), 3.62
(d, J=8.3 Hz, 1H), 7.12 (brs, 1H), 7.36–7.48 (m, 5H), 7.48
(brs, 1H) and one peak of an acid proton was missing;
13C NMR (100.40 MHz, acetone-d6): d=29.0, 35.0, 35.8,
117.3, 129.0, 129.2 (2C), 129.4 (2C), 134.1, 164.4, 167.6; IR
(KBr): n=3440, 3320, 3185, 3037, 2242 (CN), 1708
+
(FAB+): m/z=303.0905, calcd. for C16H1635ClN2O2 [M+
H]+: 303.0900.
(À)-(1R,3R)-17ev: 94% ee; colorless oil; 1H NMR
(399.65 MHz, CDCl3): d=1.56 (s, 9H), 3.00 (d, J=7.9 Hz,
1H), 3.57 (d, J=7.9 Hz, 1H), 3.82 (s, 3H), 6.94 (d, J=
8.8 Hz, 2H), 7.22 (d, J=8.8 Hz, 2H); 13C NMR
(100.40 MHz, CDCl3): d=13.7, 27.9 (3C), 34.6, 38.1, 55.4,
85.1, 111.8, 112.1, 114.6 (2C), 120.8, 129.5 (2C), 160.6, 163.7;
CD (MeCN): lext =285 (De=À0.74), 281 (À0.57), 277
(À0.78), 267 (À0.56), 250 (À1.7), 232 (+0.71), 210 (À4.2),
203 (À0.39); [a]2D7: À103.8 (c 1.0 in CHCl3); HR-MS (FAB+):
[ ACHTUNGTREN(NUG C=O)OH], 1677 ( AHCTUNRTGNNEGU ; HR-MS
(C=O)NH2), 1600 cmÀ1
+
À
À
(FAB+): m/z=231.0767,calcd. for C12H11N2O3 [M+H]+:
231.0770.
+
m/z=299.1391, calcd. for C17H19N3O2 [M+H]+: 299.1396.
(À)-(1R,3R)-17ew: 96% ee; colorless oil; 1H NMR
(399.65 MHz, CDCl3): d=1.59 (s, 9H), 3.05 (d, J=8.3 Hz,
1H), 3.67 (d, J=8.3 Hz, 1H), 7.16–7.25 (m, 3H), 7.42 (m,
1H); 13C NMR (100.40 MHz, CDCl3): d=13.0, 27.9 (3C),
To a solution of 18 (106 mg, 0.458 mmol) in dry methanol
(4.0 mL) was added a 2.0M ethereal solution of trimethylsi-
lyldiazomethane (0.70 mL, 1.40 mmol), and the mixture was
stirred at room temperature under an argon atmosphere for
6 h. After removal of the solvent under vacuum, the residue
was chromatographed on silica gel using ether/hexane (1/4
and then 1/1) to give the ester amide 19; yield: 88.4 mg
(0.362 mmol, 79%); white solid; 130.0–131.08C (from
MeOH); 1H NMR (399.65 MHz, CDCl3): d=3.11 (d, J=
8.5 Hz, 1H), 3.73 (d, J=8.5 Hz, 1H), 3.79 (s, 3H), 5.68 (brs,
1H), 6.42 (brs, 1H), 7.25–7.44 (m, 5H); 13C NMR
(100.40 MHz, CDCl3): d=28.5, 35.4, 36.3, 53.1, 116.4, 128.1
(2C), 128.9, 129.0 (2C), 131.7, 163.9, 165.9; HR-MS (FAB+):
2
32.6, 34.3, 85.3, 111.4, 111.8, 116.2 (d, JC,F =20.6 Hz), 117.2
2
4
3
(d, JC,F =13.7 Hz), 124.6 (d, JC,F =3.8 Hz), 128.8 (d, JC,F
=
1.5 Hz), 131.6 (d, 3JC,F =8.4 Hz), 161.9 (d, 1JC,F =249.5 Hz),
163.3; CD (MeCN): lext =268 (De=+1.3), 229 (À1.2), 214
(+0.11), 210 (À0.23), 208 (+0.023); [a]1D8: À85.4 (c 1.0 in
CHCl3); HRMS (FAB+): m/z=287.1194, calcd. for
C16H16FN2O2 [M+H]+: 287.1196.
+
(À)-(1R,3R)-17ex: 92% ee; colorless oil; 1H NMR
(399.65 MHz, CDCl3): d=1.58 (s, 9H), 3.03 (d, J=8.3 Hz,
1H), 3.68 (d, J=8.3 Hz, 1H), 7.21 (d, J=7.6 Hz, 1H), 7.33
(td, J=7.6, 1.2 Hz, 1H), 7.40 (td, J=8.0 , 1.2 Hz, 1H), 7.53
(dd, J=8.0, 1.2 Hz, 1H); 13C NMR (100.40 MHz, CDCl3):
d=13.4, 27.9 (3C), 35.0, 36.7, 85.3, 111.5, 111.7, 127.3, 128.1,
129.1, 130.2, 131.1, 163.3, 163.6; CD (MeCN): lext =276
(De=+0.55), 245 (+0.028), 224 (+21.4), 203 (À13.3); [a]1D8:
À53.5 (c 1.0 in CHCl3); HR-MS (FAB+): m/z=303.0889,
+
m/z=245.0933, calcd. for C13H13N2O3 [M+H]+: 245.0926.
A solution of the ester amide 19 (13.1 mg, 0.0536 mmol)
in thionyl chloride (0.50 mL) was heated under reflux for
35 h. After the solution was concentrated under vacuum, the
residue was separated by flash chromatography on silica gel
with ethyl acetate/cyclohexane (1/1) to give the cyclopro-
pane 17bq; yield: 9.1 mg (0.0402 mmol, 75%).
+
calcd. for C16H1635ClN2O2 [M+H]+: 303.0900.
(À)-(1R,3R)-17ey: 98% ee; yellow oil; 1H NMR
(399.65 MHz, CDCl3): d=1.57 (s, 9H), 2.96 (d, J=8.3 Hz,
1H), 3.60 (d, J=8.3 Hz, 1H), 3.95 (s, 3H), 6.95–7.01 (m,
2H), 7.07 (m, 1H), 7.40 (m, 1H); 13C NMR (100.40 MHz,
CDCl3): d=13.0, 27.9 (3C), 34.5, 34.7, 55.7, 84.8, 110.8,
112.2, 112.4, 118.2, 120.6, 128.3, 131.1, 158.6, 163.9; CD
(MeCN): lext =279 (De=+4.5), 246 (+0.16), 229 (+13.1),
202 (À22.7); [a]1D8: À40.2 (c 1.0 in CHCl3); HR-MS (FAB+):
Acknowledgements
The authors greatly acknowledge JSPS for supporting this
work by KAKENHI (19550112). The authors also thank Mr.
Yosuke Fujiyasu for preparation of some compounds for CD
and HR-MS analyses.
+
m/z=299.1393, calcd. for C17H19N2O3 [M+H]+: 299.1396.
(À)-(1R,3S)-17ez: 99% ee; colorless oil; 1H NMR
(495.13 MHz, CDCl3): d=1.58 (s, 9H), 2.49 (s, 3H), 3.06 (d,
J=8.5 Hz, 1H), 3.56 (d, J=8.5 Hz, 1H), 7.09 (d, J=7.9 Hz,
1H), 7.24 (t, J=7.9 Hz, 1H), 7.31–7.36 (m, 2H); 13C NMR
(100.40 MHz, CDCl3): d=13.0, 19.5, 27.9 (3C), 34.7, 37.4,
85.1, 111.8 (2C), 126.5, 127.3, 128.0, 129.8, 130.9, 138.6,
163.7; CD (MeCN): lext =267 (De=+1.0), 246 (+0.067), 223
(+11.8), 201 (À6.6); [a]1D7: À65.6 (c 0.74 in CHCl3); HR-MS
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Adv. Synth. Catal. 2010, 352, 2966 – 2978
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2977

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b=
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been deposited with the Cambridge Crystallographic
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759773. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif or on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
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2978
asc.wiley-vch.de
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2966 – 2978