Asymmetric intramolecular cyclopropanation of diazo compounds with metallosalen complexes as catalyst: Structural tuning of salen ligand

Article abstract of DOI:10.1016/S0957-4166(03)00167-8

Intramolecular cyclopropanation of alkenyl α-diazoacetates and alkenyl diazomethyl ketones was examined by using optically active (ON⁺)Ru(II)(salen) and Co(II)(salen) complexes as catalysts. For the cyclization of 2-alkenyl α-diazoacetates, Co(II)(salen) complexes 9 and 10 were found to be superior catalysts to the corresponding (ON⁺)Ru(II)(salen) complexes 4 and 5. On the other hand, (ON⁺)Ru(II)(salen) complex 2 was found to be the catalyst of choice for the cyclization of 3-alkenyl diazomethyl ketones, and complex 4 was found to be a good catalyst for the cyclization of (E)-4-alkenyl diazomethyl ketones. The present study demonstrates that metallosalen complexes, especially optically active (ON⁺)Ru(II)(salen) and Co(II)(salen) complexes, can serve as efficient catalysts for the cyclization of alkenyl diazocarbonyl compounds, if a suitable salen ligand is used as the chiral auxiliary.

Full text of DOI:10.1016/S0957-4166(03)00167-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 823–836
Asymmetric intramolecular cyclopropanation of diazo compounds
with metallosalen complexes as catalyst: structural tuning of
salen ligand
Biswajit Saha, Tatsuya Uchida and Tsutomu Katsuki*
Department of Chemistry, Faculty of Science, Graduate School, Kyushu University 33, CREST,
Japan Science and Technology (JST), Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Received 16 January 2003; accepted 4 February 2003
Abstract—Intramolecular cyclopropanation of alkenyl a-diazoacetates and alkenyl diazomethyl ketones was examined by using
optically active (ON+)Ru(II)(salen) and Co(II)(salen) complexes as catalysts. For the cyclization of 2-alkenyl a-diazoacetates,
Co(II)(salen) complexes 9 and 10 were found to be superior catalysts to the corresponding (ON+)Ru(II)(salen) complexes 4 and
5. On the other hand, (ON+)Ru(II)(salen) complex 2 was found to be the catalyst of choice for the cyclization of 3-alkenyl
diazomethyl ketones, and complex 4 was found to be a good catalyst for the cyclization of (E)-4-alkenyl diazomethyl ketones. The
present study demonstrates that metallosalen complexes, especially optically active (ON+)Ru(II)(salen) and Co(II)(salen) com-
plexes, can serve as efficient catalysts for the cyclization of alkenyl diazocarbonyl compounds, if a suitable salen ligand is used as
the chiral auxiliary. © 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
been extensively studied using transition metal com-
plexes as catalysts. Thus far, excellent catalysts such as
Cu[bis(oxazoline)s],4 Cu(semicorrin),5 Cu(diamine),6
Ru(Pybox),7 Rh(MEPY) and its related complexes,8
Molecules possessing a cyclopropane-ring substructure
have received much attention because of their synthetic
utility as building blocks and their occurrence as sub-
units of many natural products. Thus, a number of
methodologies for the construction of cyclopropane
units have already been reported. Among them, transi-
tion metal-catalyzed cyclopropanation of olefins with
diazo compounds as carbenoid precursors is a highly
useful method in terms of its simplicity and mild reac-
tion conditions.1 Furthermore, use of transition metal
complexes bearing appropriate chiral ligand(s) enables
control of the stereochemistry of the cyclopropana-
tion.1,2 Therefore, many transition metal complexes
with chiral ligands have been prepared and employed as
catalysts for asymmetric cyclopropanation.1,2 Conse-
quently, highly diastereo- (trans- or cis-) and enantiose-
lective intermolecular cyclopropanations have been
achieved in the last three decades.1–3 In parallel with
these studies, intramolecular cyclopropanation of dia-
zocarbonyl compounds, which is an efficient method
for construction of [n.1.0]bicyclic structures, has also
Rh2(S-DOSP)2,9
(R)-b-cis-[Ru(II)(biaryldiamine)-
(CH3CN)2]10 have been introduced and high enantiose-
lectivity has been achieved in the intramolecular cyclo-
propanation of various kinds of a-diazocarbonyl
compounds. Attempts have also been made using chiral
Cu(I) complexes of biferrocene-based bis(oxazoline),11
Ru(II)-diphenyl phosphino(oxazolinyl) quinoline,12 Ru-
based porphyrin,13 though the enantioselectivity
was moderate. However, the scope of each intramolecu-
lar cyclization reaction has been rather limited. For
examples, chiral dirhodium(II)carboxamide complexes
introduced by Doyle et al. are by far the best catalysts
for cyclization of alkenyl diazoacetates and diazo-
acetamides,8 although they are not very efficient for
the cyclization of alkenyl a-diazoketones.14 On the
other hand, cyclization of alkenyl diazomethyl ketones
with Cu(semicorrin) catalyst shows modest to high
enantioselectivity (up to 95% ee), though it is less
efficient for the cyclization of alkenyl a-diazoacetates.5
Recently, Pe´rez-P´ıetro et al. reported that a rhodium
complex, bearing a unique o-metallated aryl phos-
phine ligand, catalyzed cyclization of 4-alkenyl
and 3-alkenyl diazomethyl ketones with good to
* Corresponding author. Fax: +81-92-642-2607; e-mail: katsuscc@
mbox.nc.kyushu-u.ac.jp
0957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00167-8

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B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
high enantioselectivity (up to 95% and 80% ees,
respectively).15
catalyzes cyclopropanation of styrene with t-butyl a-
diazoacetate in a highly trans- and enantioselective
manner,19 which chiral (ON+)Ru(II)(salen)
2 and
Despite the introduction of such excellent catalysts, no
general catalyst for cyclization of alkenyl a-diazoesters
and a-diazoketones is so far available. This might be
mainly attributed to the fact that the transition state
conformation of each cyclization varies with the sub-
strate used.14 It was considered to be difficult to control
a wide variety of transition state conformations with
only one catalyst. In contrast, use of a series of cata-
lysts that can be readily derived from partial modifica-
tion of a parent catalyst was considered to be a more
attractive strategy for developing the general cyclization
of alkenyl a-diazoesters and a-diazoketones.1,2 We have
recently demonstrated that some metallosalen com-
plexes [hereafter denoted as M(salen)s] such as chiral
Co(III)(salen), Co(II)(salen), and (ON+)Ru(II)(salen)
serve as efficient catalysts for intermolecular cyclo-
propanation.3,16 As various types of salen ligands are
easily derived from commercial or readily synthesized
diamine and salicylaldehyde derivatives, the structure of
M(salen)s was considered to be tunable in compliance
with the substrate used and, therefore, M(salen)s were
considered to be good candidates for the catalysts of
various intramolecular cyclizations. Thus, we examined
intramolecular cyclopropanation of alkenyl a-
diazoesters17 and of alkenyl diazomethyl ketones18
using chiral M(salen)s as the catalysts.
Co(II)(salen) 3 do in a highly cis- and enantioselective
manner (Scheme 1).3 It is also worth noting that com-
plexes 2 and 3 show the opposite sense of enantioselec-
tion to each other, though they carry the same salen
ligand. Based on this contrasting catalysis by Co- and
Ru-(salen)s, we expected that the stereochemistry of
cyclization of alkenyl a-diazoesters and of alkenyl dia-
zomethyl ketones could be regulated by using appropri-
ately designed Co- and Ru-(salen)s as the catalysts.
Accordingly, we first examined the cyclization of (E)-
cinnamyl a-diazoacetate 7a using complexes 1–3 as
catalysts. The cyclization of Co(salen)s 1 and 3 was
very slow when the reaction was carried out in 0.01 M
substrate concentration. On the other hand, (ON+
)Ru(II)(salen) 2 catalyzed the desired reaction under the
same reaction conditions, except that the reaction
medium was irradiated with incandescent lamp.3b Com-
plex 2 is coordinatively saturated and catalytically inac-
tive. Therefore, photo-irradiation that promotes
dissociation of the apical NO ligand and makes the
catalyst active is indispensable for the present reaction
(Scheme 2).17,20 The enantioselectivity of the cyclization
was moderate (70% ee), but the chemical yield was
insufficient because dimerization of the diazoester form-
ing the corresponding maleic and fumaric esters
occurred competitively. Thus, the cyclization was per-
formed under high dilution conditions to suppress the
dimerization: a 0.074 M solution of the diazoester was
added dropwise to the reaction medium including 3
over 24 h. Under the conditions, moderate enantioselec-
tivity (70% ee) and acceptable chemical yield were
obtained (Table 1, entry 1).
2. Results and discussion
2.1. Intramolecular cyclopropanation of 2-alkenyl a-dia-
zoacetates using metallosalen complexes
We have already reported that chiral Co(III)(salen) 1
Scheme 1.

B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
825
Scheme 2.
In the cyclopropanation using (ON+)Ru(II)(salen) 2 as
the catalyst, alkenes have been considered to approach
the intermediary carbenoid species along RuꢀO bond
axis.3b In contrast to the intermolecular cyclopropana-
tion, the intermediary carbenoid species in the cycliza-
tion of (E)-cinnamyl a-diazoacetate 7a is linked to the
alkenyl moiety. The linker necessarily causes steric
repulsion with the 2¦-phenyl group of the salen ligand
upon the approach of the alkenyl moiety along the
RuꢀO bond (Fig. 1). Thus, we considered that the
alkenyl moiety would approach the carbenoid species
along the RuꢀN2 bond, reflecting the ligand conforma-
tion:16,21 the alkenyl moiety would approach from the
downwardly-bent naphthalene ring side of 2. We also
assumed that the CꢁO bond and the CꢁRu bond in the
Table 1. Asymmetric intramolecular cyclopropanation of
(E)-cinnamyl a-diazoacetate 7a using (ON+)Ru(II)(salen)
complexes as catalysts under high dilution conditions
Entry
Catalyst
Yield (%)
% eea
Config.b
1
2
3
4
2
4
5
6
66
58
54
62
70
67
82
55
1S,5R,6R
1S,5R,6R
1S,5R,6R
1S,5R,6R
a Enantiomeric excess was determined by GLC analysis using CHI-
RAL b-DEX column operated at 160°C.
b Determined by comparison with the reported specific rotation.
[h]D24.5 −90 (c 0.25, chloroform) (82% ee), [lit.8a [h]2D3 +130 (c 0.29,
chloroform) for 1R,5S,6S-isomer].
Figure 1.

826
B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
carbenoid moiety would take antiperiplanar conforma-
tion, based on the proposal made by Doyle et al.22 We
further assumed that the alkenyl moiety would
approach in a skewed-perpendicular manner to the
CꢁRu bond3,8a,19,23 and that the moiety rotates clock-
wise as the reaction proceeds.3a These assumptions led
us to the transition state model for the cyclization as
described in Fig. 1. The model suggested that steric
repulsion exists between the linker and the 2¦-sub-
stituent (R) and the repulsion destabilizes the transition
state, reducing enantioselectivity, especially when the
2¦-substituent is bulky. Thus, we prepared complexes 4
and 5 bearing a small or no substituent at C2¦ and
examined the cyclization with them. Although the reac-
tion with complex 4 showed moderate enantioselectiv-
ity, use of complex 5 improved enantioselectivities up to
82% ee (entries 2 and 3). We also examined the reaction
with complex 6 as the catalyst but enantioselectivity
was only moderate (entry 4). It is, however, noteworthy
that the sense of asymmetric induction by complex 6 is
opposite to that by complexes 2, 4, and 5. These results
suggest that the approach of the alkenyl moiety is
dictated by the ligand conformation, which is primarily
determined by the chirality of the diamine unit.16 The
configuration of the products was compatible with the
proposed transition state model. The cyclization of
several other 2-alkenyl a-diazoacetates with 4 or 5 as
the catalyst was next examined (Table 2) but good
substrates for the cyclization were found to be limited
to (E)-2-alkenyl a-diazoactates. The cyclizations of Z-
and 2-substituted alkenyl diazoacetates were less enan-
tioselective. The Z-substituent was considered to cause
steric repulsion with the CꢁO bond, especially upon the
rotation of the alkenyl moiety and the C2 substituent
(R3) of the alkenyl moiety to cause with the salen
ligand. These steric repulsions, especially the latter one,
destabilized the desired transition state and reduced the
enantioselectivity.
In the intermolecular cyclopropanation using
Co(II)(salen) 3 as the catalyst, olefin has been consid-
ered to approach the intermediary carbenoid species
along CoꢀN2 bond axis.3a The above transition state
model for the (ON+)Ru(II)(salen)-catalyzed cyclization
has also indicated that the alkenyl moiety approaches
along the CoꢀN2 bond axis. Therefore, Co(II)(salen) 3
or its derivatives was expected to be a better catalyst for
the cyclization than (ON+)Ru(II)(salen)s 2, 4, and 5,
though Co(II)(salen) 3 had shown very poor catalytic
activity in the preliminary study (vide supra). Thus, we
re-examined the cyclization of (E)-cinnamyl a-diazoac-
etate using complex 3 as the catalyst under much higher
substrate concentration in the presence of N-methylimi-
dazole.24,25 The desired reaction proceeded slowly with
moderate enantioselectivity, however, the undesired
dimerization did not occur under the conditions (Table
3, entry 2). Based on the effect of the ligand structure
on enantioselectivity observed in the (ON+
)Ru(II)(salen)-catalyzed reaction (vide supra), we next
examined the cyclization with complex 10 and found
that the reaction proceeded with excellent enantioselec-
tivity of 96% ee, though the chemical yield was still
Table 2. Effect of olefinic substituent on enantioselectivity in the reactions using 4 or 5 as catalyst
Entry
Substrate
Catalyst
R1
R2
R3
Temp. (°C)
Yield (%)
% eea
1b
2
3
7b
7c
7d
7e
7e
7f
5
4
4
4
4
5
5
5
p-ClC6H4
p-BrC6H4
p-MeOC6H4
PhCꢂC
PhCꢂC
H
H
H
H
H
H
H
H
H
H
H
H
Me
3
37
37
10
0
37
37
37
62
56
63
51
31
24
44
18
87c
87d
87e
78f
79f
14e
40h
8i
4
5g
6
H
Ph
Me
H
7
8
7g
7h
Ph
Ph
a Absolute configuration has not been determined.
b Reaction was carried out with starting material (0.1 mmol) and THF (9 ml).
c Enantiomeric excess was determined by HPLC analysis using chiral column (DAICEL CHIRALPAK AD, hexane:isopropanol=19:1,
temperature=40°C).
d Enantiomeric excess was determined by HPLC analysis using chiral column (DAICEL CHIRALPAK AD×2, hexane:isopropanol=15:1, rt).
e Enantiomeric excess was determined by HPLC analysis using chiral column (DAICEL CHIRALPAK AD, hexanne:isopropanol=15:1, rt).
f Enantiomeric excess was determined by HPLC analysis using chiral column (DAICEL CHIRALCEL OD-H, hexane:isopropanol=20:1,
temperature=40°C).
g Amount of THF was 1 ml.
h Enantiomeric excess was determined by HPLC analysis using chiral column (DAICEL CHIRALCEL OB-H, hexane:isopropanol=15:1, rt).
i Enantiomeric excess was determined by GLC analysis using CHIRAL b-DEX column operated at 200°C.

B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
827
Table 3. Intramolecular cyclopropanation of (E)-cinnamyl a-diazoacetate using Co(II)-salen complexes as catalysts
Entry
Catalyst
THF (ml)
NMI (mmol)
Yield (%)
% eea
Config.b
1
2
3
4
5
3
3
10
10
9
7
1
1
0.2
0.2
–
–
–
–
0.01
0.01
0.1
0.1
15
24
75
67
75
96
95
97
1S,5R,6R
1S,5R,6R
1S,5R,6R
1S,5R,6R
a Enantiomeric excess was determined by GLC analysis using CHIRAL b-DEX column operated at 160°C.
b Determined by comparison of specific optical rotation with the reported one. [h]D24.5 −127 (c 0.25, chloroform) (97% ee) (entry 5), [lit.8a [h]D23 +130
(c 0.29, chloroform) for 1R,5S,6S-isomer].
modest (entry 3). Further increase of substrate concen-
tration improved the chemical yield to an acceptable
level without decaying enantioselectivity (entry 4).
Under the same conditions, the reaction with complex 9
also showed excellent enantioselectivity as well as
acceptable chemical yield (entry 5). The configuration
of the products obtained were compatible with the
approach of alkenyl moieties along CoꢀN2 bond axis.
presence of a bulky Z-substituent like phenyl group is
considered to destabilize the desired transition state and
to decrease enantioselectivity (see Fig. 1). Introduction
of a substituent at C2 also affected enantioselectivity
adversely (entry 21), as observed in the (ON+
)Ru(II)(salen)-catalyzed reaction (vide supra).
Co(salen) and Ru(salen) possessing the same ligand
showed similar catalytic performances: (E)-alkenyl dia-
zoesters are the good substrates, 2-substituted alkenyl
diazo compounds are poor substrate and both the Co-
and Ru-(salen)s show the same sense of asymmetric
induction, though the degrees of their asymmetric
induction differ to considerable extent. As expected,
these results suggested that the transition state confor-
mation for Co(salen)-catalyzed cyclization is similar to
that for (ON+)Ru(II)(salen)-catalyzed cyclization (vide
supra).
2.2. Intramolecular cyclopropanation of alkenyl dia-
zomethyl ketones
Accordingly, we examined the cyclization of various
2-alkenyl a-diazoacetates 7b–k using complexes 9 and
10 as catalysts. Good to excellent levels of enantioselec-
tivities have been realized in the cyclization of (E)-2-
alkenyl a-diazoacetates (Table 4, entries 1–13).
With these results in hand, we next examined the
cyclization of 3-alkenyl diazomethyl ketones. Only a
few catalysts have been successfully applied to the
stereocontrol of the cyclization of this class of com-
pounds, as described earlier.1,2,5,15 The cyclization of
(E)-1-diazo-6-phenyl-5-hexen-2-one 11a was first car-
ried out with (ON+)Ru(II)(salen) complex 5 as the
catalyst under photo-irradiation conditions. The desired
cyclization proceeded with a good yield but enantiose-
lectivity of the cyclization was moderate (58% ee)
(Table 5, entry 1). The cyclization with complex 4 also
showed only moderate enantioselectivity (entry 2). In
contrast to the cyclization of (E)-cinnamyl a-diazoac-
etate, however, the cyclization with 2 showed excellent
enantioselectivity together with acceptable chemical
yield (entry 3). The cyclization with complex 6 showed
low enantioselectivity, though it proceeded smoothly
(entry 4). It is noteworthy that the sense of enantiose-
lection by complex 6 is opposite to that by complexes 2,
4, and 5. This suggests that the approaching path of the
alkenyl moiety is mainly dictated by the conformation
Amongst them, the cyclization of (E)-cinnamyl a-dia-
zoacetate derivatives showed high enantioselectivity
greater than 95% (entries 1–6). Cyclization of (E)-5-
phenylpent-2-en-4-yn-1-yl a-diazoacetates with complex
9 also showed high enantioselectivity of 93% ee, though
the chemical yield was moderate (entry 7). It is note-
worthy that cyclization of non-conjugated (E)-2-alkenyl
a-diazoacetates also proceeded with a good enantiose-
lectivity of 79% ee, though slightly elevated reaction
temperatures were needed to obtain an acceptable
chemical yield (entry 11). Cyclization of 3,3-disubsti-
tuted substrates proceeded with good to high enantiose-
lectivity, though higher reaction temperature was
required in the cyclization of the substrate bearing
Z-phenyl group (entries 14–18). Cyclization of (Z)-cin-
namyl a-diazoacetates proceeded with moderate enan-
tioselectivity but the reaction was slow (entry 19). The

828
B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
Table 4. Asymmetric intramolecular cyclopropanation using Co(II)-salen complexes 9 and 10 as catalyst
Entry
Substrate
Catalyst
R1
R2
R3
Yield (%)
% ee
1
2
3
4
5
6
7
8
7b
7b
7c
7c
7d
7d
7e
7e
7i
7i
7i
7i
7k
7g
7g
7j
7j
7j
9
10
9
10
9
p-ClC6H4
p-ClC6H4
p-BrC6H4
p-BrC6H4
p-MeOC6H4
p-MeOC6H4
Ph-CꢂC
Ph-CꢂC
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
(CH3)2CH
Ph
Ph
Ph
Ph
Ph
H
H
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
72
88
70
52
70
93
32
24
10
48
81
18
34
70
47
23
65
35
16
24
12
98a
96a
97b
96b
98a
96a
93c
84c
91d
82d
79d
73d
75g
90h
91h
79i
10
9
10
10
10
10
9
10
9
10
10
10
9
9
10e
11f
12f
13e
14
15
16
17e
18
19
20
21f
H
Me
Me
Ph
Ph
Ph
Ph
H
74i
81i
7f
7f
7h
9
10
10
74a
68a
38d
H
a Enantiomeric excess was determined by HPLC analysis using chiral column (DAICEL CHIRALPAK AD, hexane:isopropanol=15:1).
b Enantiomeric excess was determined by HPLC analysis using chiral column (DAICEL CHIRALPAK AD×2, hexane:isopropanol=15:1).
c Enantiomeric excess was determined by HPLC analysis using chiral column (DAICEL CHIRALPAK AD, hexane:isopropanol=20:1).
d Enantiomeric excess was determined by GLC analysis using CHIRAL b-DEX column operated at 160°C.
e Reaction was carried out at 35°C in the presence of 2 equiv. of N-methylimidazole.
f Reaction was carried out at 45°C in the presence of 2 equiv. of N-methylimidazole.
g Enantiomeric excess was determined by GLC analysis using CHIRAL b-DEX column operated at 120°C.
h Enantiomeric excess was determined by HPLC analysis using chiral column (DAICEL CHIRALCEL OB-H hexane:isopropanol=15:1).
i Enantiomeric excess was determined by HPLC analysis using chiral column (DAICEL CHIRALPAK AD, hexane:isopropanol=9:1).
Table 5. Cyclization of (E)-1-diazo-6-phenyl-5-hexen-2-one
11a
of the salen ligand, as discussed in the cyclization of
alkenyl a-diazoacetate (vide supra).16 On the other hand,
Co(salen)s 3, 9, and 10 showed no catalytic activity for
this cyclization even under high substrate concentration.
Accordingly, we further examined the cyclization of
several other 3-alkenyl diazomethyl ketones 11b–f using
complex 2 as the catalyst (Table 6). Good to excellent
enantioselectivities as well as chemical yields were
obtained in the reaction examined, except that the
reaction of 3-substituted alkenyl diazomethyl ketone 11f
showed only modest enantioselectivity (entry 5). It is
worth noting that the reactions of non-conjugated
alkenyl diazomethyl ketones proceeded smoothly with
high enantioselectivity (entries 1 and 2). The reaction of
(Z)-3-alkenyl diazomethyl ketone, (Z)-1-diazo-6-phenyl-
5-hexen-2-one, showed somewhat reduced enantioselec-
tivity (79% ee, entry 4).
Entry
Catalyst
Yield (%)
% eea Elution orderb
1
2
3
4
5
4
2
6
62
60
78
81
58
44
94
12
+
+
+
–
a Determined by HPLC analysis using chiral column (DAICEL CHI-
RALCEL OD-H, hexane:isopropanol=9:1).
We also examined (ON+)Ru(II)(salen)-catalyzed cycli-
zation of 4-alkenyl diazomethyl ketones (Table 7).
b Plus sign means that the major enantiomer is eluted fast and minus
sign means that the minor enantiomer is eluted fast.

B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
829
Table 6. Cyclization of 3-alkenyl diazomethyl ketones 11b–f with 2 as the catalyst
Entry
Substrate
R1
R2
R3
Yield (%)
% ee
1
2
3
4
5
11b
11c
11d
11e
11f
(CH3)2ꢁCH(CH2)2
CH3
CH3
H
Ph
H
H
H
H
H
72
65
82
62
31
93a
87b
84c
79d
12e
CH3
PhCꢂC
H
Ph
CH3
a Determined by GLC analysis using a 30 m×0.25 mm CHIRAL SUPELCO b-DEX column [column temperature: 130°C for 70 min, then
programmed to 180°C at 5°C/min, and 180°C for 30 min]: 76.53 min (minor enantiomer), 77.31 min (major enantiomer)].
b Determined by GLC analysis using a 30 m×0.25 mm CHIRAL SUPELCO b-DEX column [column temperature: 90°C for 30 min, then
programmed to 110°C at 2°C/min, and 110°C for 30 min]: 41.38 min (minor enantiomer), 41.94 min (major enantiomer)]. Absolute configuration
was determined to be 2R,3S by comparing the reported specific optical rotation: [h]2D4 +45 (c 0.2, chloroform) (87% ee), [lit.31 [h]D23 −34.3 (c 1.0
chloroform) for 2S,3R-isomer (63% ee)].
c Determined by HPLC analysis using chiral column (DAICEL CHIRALCEL OJ-H, hexane:isopropanol=3:1).
d Determined by HPLC analysis using chiral column (DAICEL CHIRALCEL OJ-H, hexane:isopropanol=20:1).
e Determined by HPLC analysis using chiral column (DAICEL CHIRALCEL OD-H hexane:isopropanol=9:1).
Table 7. Intramolecular cyclopropanation of 4-alkenyl diazoketones 13a–e with (ON+)Ru(II)(salen) complexes as catalysts
Entry
Substrate
Catalyst
R1
R2
Yield (%)
% ee
1
2
3
4
5
6
7
8
13a
13a
13a
13a
13b
13c
13d
13e
2
4
5
6
4
4
4
4
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
Me
42
63
56
45
44
72
46
36
54a
88a
71a
13a
89a
77b
33c
5d
p-ClC6H4
p-MeOC6H4
H
Ph
a Determined by HPLC analysis using chiral column (DAICEL CHIRALCEL OD-H, hexane:isopropanol=9:1).
b Determined by HPLC analysis using chiral column (DAICEL CHIRALCEL OJ-H, hexane:isopropanol=4:1).
c Determined by GLC analysis using a 30 m×0.25 mm CHIRAL SUPELCO b-DEX column.
d Determined by HPLC analysis using chiral column (DAICEL CHIRALCEL OJ-H, hexane:isopropanol=50:1).
We first examined the cyclization of (E)-1-diazo-7-
phenyl-6-hexen-2-one 13a with (ON+)Ru(II)(salen) 2 as
the catalyst (entry 1). Although the desired cyclization
proceeded, enantioselectivity was moderate. The
cyclization using complex 4 as the catalyst, however,
showed high enantioselectivity of 88% (entry 2). Com-
plex 5 was a less efficient catalyst (entry 3). Based on
these results, we examined the cyclization of other
4-alkenyl diazomethyl ketones with complex 4 as the
catalyst and found that the reactions of other (E)-sub-
strates also showed moderate to good enantioselectivity
(entries 5 and 6). Cyclization of non- and di-substituted
alkenyl diazoketones (13d and 13e), however, showed
only modest enantioselectivity (entries 7 an 8).
3. Conclusion
It is well known that the catalyst of choice for asym-
metric intramolecular cyclopropanation of alkenyl
diazo compounds varies with the substrate used, proba-
bly because the transition state conformation for each

830
B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
4.2. Synthesis of (ON+)Ru(II)(salen) complex 5
cyclization is strongly affected by several factors: the
substitution pattern of the alkenyl moiety of the sub-
strate, the length and the nature of the linker connect-
ing the alkenyl and diazomethyl moieties, and metal
ion.1,2,14 This requires introduction of a structurally
tunable catalyst in compliance with the substrate used.
In this study, we were able to demonstrate that ruthe-
nium and cobalt complexes carrying a salen ligand
which can be readily modified are promising catalysts
for asymmetric intramolecular cyclopropanation of var-
ious types of alkenyl diazo compounds.
Complex 5 was prepared according to an earlier
reported procedure,3b except for the purification. The
reaction mixture was concentrated under vacuum and
the residue was purified quickly through SiO2 chro-
matography using CH2Cl2/acetone (50:1) as eluent and
the eluate was concentrated. Crystallization of the
residue from CH2Cl2 and acetone afforded the desired
complex as brown solid in 16% yield.
1H NMR (400 MHz): l 8.57 (s, 1H), 8.38 (s, 1H), 8.09
(d, J=8.0 Hz, 1H), 8.01–7.82 (m, 5H), 7.70–7.60 (m,
2H), 7.56–7.48 (m, 2H), 7.39–7.27 (m, 2H), 7.19 (t,
J=7.7 Hz, 1H), 7.15–7.0 (m, 8H), 6.79–6.76 (m, 2H),
6.60 (t, J=7.7 Hz, 1H), 4.06 (br-t, J=10.5 Hz, 1H),
3.24 (br-q, J=8.5 Hz, 1H), 2.81 (br-s, 1H), 2.62 (br-s,
1H), 2.04–2.0 (br-m, 2H), 1.67–1.37 (br-m, 4H). IR
(KBr): 3043, 2931, 2858, 2364, 2339, 1830, 1641, 1577,
1614, 1544, 1444, 1423, 1348, 1315, 1226, 1188, 1147,
1122, 1028, 952, 873, 777, 750, 688, 572, 538, 424 cm−1.
Anal. calcd for C48H36ClN3O3Ru·H2O: C, 67.24; H,
4.47; N, 4.90. Found: C, 67.35; H, 4.52; N, 4.90%.
4. Experimental
4.1. General
1H NMR spectra were recorded at 400 or 270 MHz on
BRUKER DPX-400, JEOL GX-400, or JEOL EX-270
instruments. All signals were expressed as ppm down
field from tetramethylsilane used as internal standard (l
value in CDCl3). IR spectra were obtained with a
SHIMADZU FTIR-8600 instrument. Optical rotations
were measured with a JASCO P-1020 polarimeter. High
resolution EI mass spectra were obtained from JEOL
JMX-SX/SX 102A spectrometer. Column chromatogra-
phy was conducted on silica gel BW-820MH, 70–200
mesh ASTM, available from FUJI SILYSIA CHEMI-
CAL LTD. Enantiomeric excesses were determined by
HPLC analysis using SHIMADZU LC-10AT-VP and
SHIMADZU GC–17A equipped with an appropriate
optically active column, as described in the footnotes of
the corresponding tables. Solvents were dried and dis-
tilled shortly before use. Reactions were performed
under nitrogen if necessary.
4.3. Synthesis of 2-alkenyl a-diazoacetates
4.3.1. (E)-3-(4-Chlorophenyl)-2-propen-1-yl a-diazo-
acetate 7b. Diketene (0.47 mL, 6.1 mmol) in THF (2.5
mL) was added dropwise to a stirred solution of (E)-3-
(4-chlorophenyl)-2-propen-1-ol (1.22 g, 4.81 mmol) and
anhydrous NaOAc (26.3 mg, 0.33 mmol) in THF (10
mL) under refluxing conditions. The resulting solution
was heated at reflux for 2 h. After cooling to room
temperature, Et2O (10 mL) and brine (5 mL) were
added and the layers were separated. The aqueous layer
was washed with Et2O (2×15 mL). The combined
organic layers were washed with brine and dried over
anhydrous MgSO4. The solvent was removed under
reduced pressure and the brown residue was chro-
matographed on silica gel (hexane/EtOAc=9:1) to
afford (E)-3-(4-chlorophenyl)-2-propen-1-yl acetoac-
etate as a colorless liquid in 84% yield.
Co(III)salen complex 1,19b Co(II)salen complexes 3, 9,
and 10,3a and (ON+)Ru(II)(salen) complexes 2, 4, and
6
3b were prepared according to the reported procedures.
(E)-3-(4-Chlorophenyl)-2-propen-1-ol, (E)-3-(4-bromo-
phenyl)-2-propen-1-ol, and (E)-3-(4-methoxyphenyl)-2-
propen-1-ol were prepared from the corresponding acid
by the sequence: (i) esterification with methanol in the
presence of a catalytic amount of conc. H2SO4 and (ii)
reduction with DIBAL-H.26 (E)-5-Phenylpent-2-en-4-
yn-1-ol, (E)-3-phenyl-2-methyl-2-propen-1-ol, (E)-5-
phenyl-2-penten-1-ol, 3,3-diphenyl-2-propen-1-ol were
prepared from the corresponding a,b-unsaturated ester
by the reduction with DIBAL-H.26 (E)-Cinnamyl a-dia-
zoacetate 7a and (Z)-cinnamyl a-diazoacetate 7f were
prepared according to the literature procedures.8a 5-
Bromo-1-phenylpent-3-en-1-yne, (Z)-cinnamyl bro-
mide, and (E)-4-bromo-1-methyl-1-phenyl-1-propene
were prepared from the corresponding alcohols by
treatment with PBr3.27 4-Bromo-1-phenyl-1-butene was
prepared according to the literature procedure.28 4-
A solution of methanesulfonyl azide (0.56 g, 4.65
mmol) in acetonitrile (4 mL) was added dropwise over
10 min to a stirred solution of (E)-3-(4-chlorophenyl)-2-
propen-1-yl acetoacetate (1.07 g, 4.23 mmol) and Et3N
(0.46 g, 0.64 mL, 4.6 mmol) in anhydrous acetonitrile (5
mL). The resulting yellow solution was monitored by
TLC and stirred at room temperature until the acetoac-
etate was consumed (ca. 4 h). A 10% aqueous NaOH
solution (5 mL) was added to the reaction mixture,
stirred for 2 h, and diluted with water. The organic
layer was separated and the water layer was washed
twice with Et2O/EtOAc (3:1, 15 mL). The combined
organic layers were washed with brine and dried over
MgSO4. The solvent was removed under reduced pres-
sure and the resulting orange residue was chro-
matographed on silica gel (hexane/EtOAc=19:1) to
Bromo-1-(4-chlorophenyl)-1-butene,
4-bromo-1-(4-
methoxyphenyl)-1-butene, and (E)-5-bromo-2-phenyl-
2-pentene were prepared according to the procedure
reported for the preparation of 4-bromo-1-phenyl-
butene.28 All these compounds gave satisfactory 1H
NMR and MS data.
1
give 7b in 68% yield. 7b: a yellow solid, mp 34°C. H
NMR (270 MHz): l 7.33 (d, J=8.3 Hz, 2H), 6.85 (d,
J=8.3 Hz, 2H), 6.60 (d, J=15.9 Hz, 1H), 6.25 (dt,
J=15.9, 6.5 Hz, 1H), 4.81 (dd, J=6.5, 1.2 Hz, 2H),

B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
831
4.79 (br-s, 1H). IR (KBr): 3112, 2119, 1685, 1591, 1490,
1394, 1338, 1197, 1153, 1087, 974, 943, 846, 798, 736,
476 cm−1. HREIMS m/z, calcd for C11H9ClN2O2 (M+):
236.0353. Found: 236.0357.
1444, 1344, 1236, 1176, 1006, 964, 920, 854, 740, 700
cm−1. Anal. calcd for C12H12N2O2: C, 66.65; H, 5.59; N,
12.95. Found: C, 66.66; H, 5.63; N, 12.92%.
4.3.7. (E)-5-Phenyl-2-penten-1-yl a-diazoacetate 7i. (E)-
5-Phenyl-2-penten-1-ol (0.32 g, 1.98 mmol) was con-
verted to 7i in 85% overall yield, following the same
4.3.2. (E)-3-(4-Bromophenyl)-2-propen-1-yl a-diazo-
acetate 7c. (E)-3-(4-Bromophenyl)-2-propen-1-ol (2.26
g, 10.6 mmol) was converted to 7c in 47% yield, follow-
ing the same procedure as that described for 7b. 7c: a
1
procedure as that described for 7b. 7i: a yellow oil. H
NMR (400 MHz): l 7.30–7.16 (m, 5H), 5.81 (dt, J=
15.2, 6.4 Hz, 1H), 5.62 (ddt, J=15.2, 6.4, 1.4 Hz, 1H),
4.74 (br-s, 1H), 4.59 (dd, J=6.4, 1.4 Hz, 2H), 2.71 (t,
J=7.8 Hz, 2H), 2.38 (dt, J=7.8, 6.4 Hz, 2H). IR (neat):
3112, 3026, 2929, 2854, 2110, 1691, 1494, 1452, 1390,
1353, 1240, 1178, 970, 742, 700 cm−1. Anal. calcd for
C13H14N2O2: C, 67.81; H, 6.13; N, 12.17. Found: C,
67.89; H, 6.17; N, 12.17%.
1
yellow solid, mp 37°C. H NMR (270 MHz): l 7.44 (d,
J=8.3 Hz, 2H), 7.25 (d, J=8.3 Hz, 2H), 6.58 (d,
J=15.8 Hz, 1H), 6.27 (dt, J=15.8, 6.3 Hz, 1H), 4.80
(dd, J=6.3, 1.3 Hz, 2H), 4.78 (br-s, 1H). IR (KBr):
3112, 2927, 2113, 1676, 1585, 1487, 1452, 1390, 1350,
1240, 1180, 1070, 1010, 970, 800, 740 cm−1. Anal. calcd
for C11H9BrN2O2: C, 47.00; H, 3.23; N, 9.97. Found: C,
46.99; H, 3.37; N, 9.81.
4.4. 3,3-Diphenyl-2-propen-1-yl a-diazoacetate 7j
4.3.3. (E)-3-(4-Methoxyphenyl)-2-propen-1-yl a-diazo-
acetate 7d. (E)-3-(4-Methoxyphenyl)-2-propen-1-ol
(1.40 g, 7.8 mmol) was converted to 7d in 53% yield,
following the same procedure as that described for 7b.
3,3-Diphenyl-2-propen-1-ol (0.52 g, 2.5 mmol) was con-
verted to 7j in 63% overall yield, following the same
procedure as that described for 7b. 7j: a yellow oil. H
NMR (400 MHz): l 7.4–7.17 (m, 10H), 6.18 (t, J=6.8
Hz, 1H), 4.76 (br-s, 1H), 4.72 (d, J=6.8 Hz, 2H). IR
(neat): 3057, 3026, 2110, 1693, 1629, 1598, 1577, 1492,
1444, 1388, 1357, 1334, 1128, 1240, 1178, 1109, 1076,
1026, 848, 763, 740, 700, 630 cm−1. Anal. calcd for
C17H14N2O2: C, 73.37; H, 5.07; N, 10.07. Found: C,
73.14; H, 5.13; N, 9.95%.
1
1
7d: a yellow oil. H NMR (270 MHz): l 7.33 (d, J=8.9
Hz, 2H), 6.85 (d, J=8.9 Hz, 2H), 6.60 (d, J=15.9 Hz,
1H), 6.15 (dt, J=15.8, 6.5 Hz, 1H), 4.79 (dd, J=6.5,
1.0 Hz, 2H), 4.78 (br-s, 1H), 3.80 (s, 3H). IR (KBr):
3089, 2960, 2111, 1676, 1604, 1512, 1446, 1396, 1353,
1303, 1251, 1182, 1026, 966, 846, 812, 742, 719, 505
cm−1. Anal. calcd for C12H12N2O3: C, 62.06; H, 5.21; N,
12.06. Found: C, 61.93; H, 5.25; N, 12.04%.
4.4.1. (E)-4-Methyl-2-penten-1-yl a-diazoacetate 7k8a.
(E)-4-Methyl-2-penten-1-ol (0.37 g, 3.7 mmol) was con-
verted to 7k in 67% overall yield, following the same
procedure as that described for 7b. 7k: a yellow oil.
Spectroscopic data (1H NMR and IR) were identical
with the reported ones.8a
4.3.4. (E)-5-Phenylpent-2-en-4-yn-1-yl a-diazoacetate 7e.
(E)-5-Phenylpent-2-en-3-yn-1-ol (0.77g, 4.86 mmol) was
converted to 7e in 52% overall yield, following the same
1
procedure as that described for 7b. 7e: a yellow oil. H
NMR (400 MHz): l 7.49–7.42 (m, 2H), 7.33–7.30 (m,
3H), 6.26 (dt, J=15.6, 6.0 Hz, 1H), 5.98 (d, J=15.6
Hz, 1H), 4.79 (br-s, 1H), 4.75 (dd, J=6.0, 1.4 Hz, 2H).
IR (neat): 3114, 2943, 2111, 1697, 1595, 1488, 1442,
1388, 1350, 1240, 1174, 1074, 1045, 954, 912, 736, 682
cm−1. HREIMS m/z, calcd for C13H10N2O2: 226.0742.
Found: 226.0740.
4.5. General procedure for intramolecular cyclopropa-
nation of 2-alkenyl a-diazoacetates in the presence of
(ON+)Ru(II)(salen) complex (4 or 5) as catalyst
(ON+)Ru(II)(salen) complex (3.7 mmol) was dissolved in
THF (7 mL) under N2. To the solution was added a
solution of 2-alkenyl a-diazoacetate (74 mmol) in THF
(1 mL) slowly over 24 h by using a syringe pump under
the irradiation of incandescent light. The mixture was
stirred for another 11 h and concentrated in vacuo. The
residue was chromatographed on silica gel using an
eluent suitable for each product to afford the corre-
sponding bicyclic lactone. The enantiomeric excesses of
products were determined by HPLC analysis using an
optically active column, as described in the footnotes of
Tables 1 and 2.
4.3.5. (E)-3-Phenyl-2-buten-1-yl a-diazoacetate 7g. (E)-
3-Phenyl-2-buten-1-ol (0.54 g, 3.67 mmol) was con-
verted to 7g in 48% overall yield, following the same
1
procedure as that described for 7b. 7g: a yellow oil. H
NMR (400 MHz): l 7.42–7.39 (m, 2H), 7.35–7.25 (m,
3H), 5.9 (td, J=7.2, 1.3 Hz, 1H), 4.88 (d, J=7.2 Hz,
2H), 4.77 (br-s, 1H), 2.12 (s, 3H). IR (neat): 3112, 2110,
1693, 1490, 1440, 1388, 1355, 1290, 1238, 1178, 1124,
985, 918, 740, 696, 669 cm−1. Anal. calcd for
C12H12N2O2: C, 66.65; H, 5.59; N, 12.95. Found: C,
66.55; H, 5.60; N, 12.97%.
4.3.6. (E)-2-Methyl-3-phenyl-2-propen-1-yl a-diazo-
acetate 7h. (E)-2-Methyl-3-phenyl-2-propen-1-ol (1 g,
6.74 mmol) was converted to 7h in 61% overall yield,
following the same procedure as that described for 7b.
4.5.1. (1S,5R,6R)-6-Phenyl-3-oxabicyclo[3.1.0]hexan-2-
one 8a8a. 8a was obtained by SiO2 chromatography
with hexane/EtOAc (7:3) in 54% yield as a colorless
solid; mp 104°C, [h]D24 −106 (c 0.25, CHCl3) (82% ee)
(Table 1, entry 3). Lit.8a mp 106°C, [h]2D3 +130 (c 0.29,
CHCl3) for 1R,5S,6S-isomer. 1H NMR spectrum of
this sample was identical with the reported one.8a
1
7h: a yellow oil. H NMR (270 MHz): l 7.37–7.2 (m,
5H), 6.52 (s, 1H), 4.81 (br-s, 1H), 4.73 (s, 2H), 1.89 (d,
J=1.3 Hz, 3H). IR (neat): 3111, 2110, 1695, 1492,

832
B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
4.5.2. 6-(4-Chlorophenyl)-3-oxabicyclo[3.1.0]hexan-2-one
8b. 8b was obtained by SiO2 chromatography with
hexane/EtOAc (7:3) in 62% yield as a colorless solid;
mp 130°C, [h]2D2 −103 (c 0.25, CHCl3) (87% ee) (Table 2,
4.5.7. 6-Methyl-6-phenyl-3-oxabicyclo[3.1.0]hexan-2-one
8g. 8g was obtained by SiO2 chromatography with
hexane/EtOAc (4:1) in 44% yield as a colorless solid;
mp 59°C, [h]2D2 −38 (c 0.25, CHCl3) (40% ee) (Table 2,
1
1
entry 1). H NMR (400 MHz): l 7.28 (d, J=8.6 Hz,
entry 7). H NMR (400 MHz): l 7.35–7.23 (m, 5H),
2H), 7.0 (d J=8.6 Hz, 2H), 4.47 (dd, J=9.6, 4.8 Hz,
1H), 4.41 (d, J=9.6 Hz, 1H), 2.53–2.49 (m, 1H), 2.32
(dd, J=3.2, 2.8 Hz, 1H), 2.30 (dd, J=4.0, 2.8 Hz, 1H).
IR (KBr): 1751, 1492, 1440, 1371, 1290, 1218, 1180,
1101, 1039, 1008, 962, 881, 856, 812, 754, 707, 626, 528,
495 cm−1. Anal. calcd for C11H9ClO2: C, 63.32; H, 4.35.
Found: C, 63.11; H, 4.40%.
4.54 (dd, J=10.0, 5.6 Hz, 1H), 4.36 (ddd, J=10.0, 1.2,
0.8 Hz, 1H), 2.54 (ddd, J=6.6, 5.6, 1.2 Hz, 1H), 2.46
(dd, J=6.6, 0.8 Hz, 1H), 1.49 (s, 3H). IR (KBr): 1762,
1440, 1357, 1188, 1070, 1045, 995, 968, 866, 833, 758,
698 cm−1. HREIMS m/z, calcd for C12H12O2 (M+):
188.0837. Found: 188.0839.
4.5.8. 5-Methyl-6-phenyl-3-oxabicyclo[3.1.0]hexan-2-one
8h. 8h was obtained by SiO2 chromatography with
hexane/EtOAc (4:1) in 18% yield as an oil. [h]2D3 −13 (c
4.5.3. 6-(4-Bromophenyl)-3-oxabicyclo[3.1.0]hexan-2-one
8c. 8c was obtained by SiO2 chromatography with
hexane/EtOAc (7:3) in 56% yield as a colorless solid;
mp 124°C, [h]2D2 −91 (c 0.25, CHCl3) (87% ee) (Table 2,
1
0.14, CHCl3) (8% ee) (Table 2, entry 8). H NMR (400
MHz): l 7.35–7.27 (m, 3H), 7.15 (d, J=6.8 Hz, 2H),
4.40 (d, J=9.2 Hz, 1H), 4.21 (d, J=9.2 Hz, 1H), 2.49
(d, J=3.2 Hz, 1H), 2.38 (d, J=3.2 Hz, 1H), 1.17 (s,
3H). IR (KBr): 1762, 1602, 1496, 1448, 1375, 1326,
1261, 1164, 1029, 889, 864, 742, 700 cm−1. HREIMS
m/z, calcd for C12H12O2 (M+): 188.0837. Found:
188.0838.
1
entry 2). H NMR (400 MHz): l 7.43 (d, J=8.5 Hz,
2H), 6.94 (d, J=8.5 Hz, 2H), 4.47 (dd, J=9.5, 4.6 Hz,
1H), 4.41 (d, J=9.5 Hz, 1H), 2.53–2.49 (m, 1H), 2.30
(dd, J=6.1, 2.9 Hz, 1H), 2.28 (dd, J=3.2, 2.9 Hz, 1H).
IR (KBr): 3033, 2964, 2900, 1747, 1490, 1369, 1290,
1217, 1180, 1101, 1037, 1004, 960, 875, 812, 746, 707,
626, 524, 484 cm−1. Anal. calcd for C11H9BrO2: C,
52.20; H, 3.58. Found: C, 52.25; H, 3.70%.
4.6. General procedure for intramolecular cyclopropa-
nation of 2-alkenyl a-diazoacetates in the presence of
Co(II)-salen complexes 9 or 10 as catalyst
4.5.4. 6-(4-Methoxyphenyl)-3-oxabicyclo[3.1.0]hexan-2-
one 8d. 8d was obtained by SiO2 chromatography with
hexane/EtOAc (3:2) in 63% yield as a colorless solid;
mp 79°C, [h]2D2 −101 (c 0.25, CHCl3) (87% ee) (Table 2,
2-Alkenyl a-diazoacetate (0.1 mmol) was placed in a S
tube and the tube was purged with nitrogen. To the
tube were added a 0.5 M solution of N-methylimida-
zole in THF (0.2 mL) and Co(II) salen complex (5
mmol), successively. The reaction mixture was stirred
for 24 h at room temperature and the solvent was
removed under vacuo. The residue was chro-
matographed on silica gel using an appropriate eluent
to afford the corresponding bicyclic lactone. The enan-
tiomeric excesses of products were determined by
HPLC analysis using an optically active column, as
described in the footnotes of Tables 3 and 4.
1
entry 3). H NMR (400 MHz): l 7.01 (d, J=9.5 Hz,
2H), 6.84 (d, J=8.7 Hz, 2H), 4.45 (dd, J=9.5, 4.9 Hz,
1H), 4.40 (d, J=9.5 Hz, 1H), 3.79 (s, 3H), 2.50–2.46
(m, 1H), 2.30 (dd, J=3.4, 2.9 Hz, 1H), 2.27 (dd, J=6.1,
2.9 Hz, 1H). IR (KBr): 2918, 2841, 1745, 1610, 1579,
1515, 1446, 1369, 1296, 1184, 1153, 1099, 1037, 1004,
962, 873, 819, 786, 715, 621, 542, 493 cm−1. Anal. calcd
for C12H12O3: C, 70.57; H, 5.92. Found: C, 70.47; H,
5.99%.
4.5.5.
6-(2-Phenylethynyl)-3-oxabicyclo[3.1.0]hexan-2-
4.6.1. (1S,5R,6R)-6-Phenyl-3-oxabicyclo[3.1.0]hexan-2-
one 8a. A colorless solid, 67% yield, [h]2D2 −127 (c 0.25,
CHCl3) (97% ee) (Table 3, entry 5).
one 8e. 8e was obtained by SiO2 chromatography with
hexane/EtOAc (4:1) in 51% yield as a colorless solid;
mp 71°C, [h]2D4 −107 (c 0.18, CHCl3) (78% ee) (Table 2,
1
entry 4). H NMR (400 MHz): l 7.38 (d, J=8.6 Hz,
4.6.2. 6-(4-Chlorophenyl)-3-oxabicyclo[3.1.0]hexan-2-one
8b. A colorless solid, 72% yield, [h]2D2 −118 (c 0.25,
CHCl3) (98% ee) (Table 4, entry 1).
2H), 7.32–7.16 (comp, 3H), 4.40 (dd, J=9.5, 4.6 Hz,
10H), 4.34 (d, J=9.5 Hz, 1H), 2.60 (m, 1H), 2.47 (dd,
J=6.1, 2.7 Hz, 1H), 1.95 (dd, J=3.2, 2.7 Hz, 1H). IR
(KBr): 3084, 2966, 2906, 1755, 1490, 1446, 1371, 1278,
1176, 1055, 1031, 962, 904, 867, 763, 698, 626, 532
cm−1. HREIMS m/z, calcd for C13H10O2 (M+):
198.0681. Found: 198.0689.
4.6.3. 6-(4-Bromophenyl)-3-oxabicyclo[3.1.0]hexan-2-one
8c. A colorless solid, 70% yield, [h]2D5 −102 (c 0.16,
CHCl3) (97% ee) (Table 4, entry 3).
4.6.4. 6-(4-Methoxyphenyl)-3-oxabicyclo[3.1.0]hexan-2-
one 8d. A colorless solid, 70% yield, [h]2D2 −113 (c 0.25,
CHCl3) (98% ee) (Table 4, entry 5).
4.5.6. 6-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one 8f7b,8a. 8f
was obtained by SiO2 chromatography with hexane/
EtOAc (7:3) in 24% yield as a colorless solid; mp 81°C,
[h]2D2 −32 (c 0.16, CH2Cl2) (14% ee) (Table 2, entry 6).
Lit.7b [h]2D5 −52 (c 1.01, CH2Cl2) (24% ee); mp 79–80°C.
Spectroscopic data (1H NMR and IR) of this sample
were identical with the reported ones.8a
4.6.5.
6-(2-Phenylethynyl)-3-oxabicyclo[3.1.0]hexan-2-
one 8e. A colorless solid, 32% yield, [h]2D5 −130 (c 0.175,
CHCl3) (93% ee) (Table 4, entry 7).

B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
833
4.6.6. 6-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one 8f. A col-
orless solid, 16% yield, [h]2D5 −168 (c 0.16, CH2Cl2) (74%
ee) (Table 4, entry 19).
organic layers were washed with brine and dried over
anhydrous MgSO4. The solvent was removed and the
residue was chromatographed on silica gel with hexane/
EtOAc (12:1) to afford 8-phenyl-7-octene-2,4-dione
(0.77 g) in 72% yield.
4.6.7. 6-Methyl-6-phenyl-3-oxabicyclo[3.1.0]hexan-2-one
8g. A colorless solid, 70% yield, [h]2D2 −92 (c 0.25,
CHCl3) (90% ee) (Table 4, entry 14).
A solution of methanesulfonyl azide (0.4 g, 3.38 mmol)
in acetonitrile (1 mL) was added dropwise over 5 min
to a stirred solution of 8-phenyl-7-octene-2,4-dione
(0.61 g, 2.82 mmol) and Et3N (0.47 mL, 3.38 mmol) in
anhydrous acetonitrile (10 mL). The resulting yellow
solution was stirred at room temperature for another 4
h for completion of diazo transfer. The reaction mix-
ture was quenched with aqueous NH4Cl (10 mL) and
extracted twice with Et2O (25 mL). The organic layer
was concentrated in vacuo. Then, aqueous NaOH solu-
tion (10%, 3 mL) was added to the crude 3-diazo-8-
phenyl-7-octene-2,4-dione, stirred for 30 min, diluted
with water (10 mL) and extracted twice with Et2O/
EtOAc (3:1, 25 mL). The combined organic layers were
washed with brine, dried over anhydrous MgSO4, and
concentrated under reduced pressure. The orange
residue was chromatographed on silica gel with hexane/
EtOAc (10:1) to give 11a in 64% yield. 11a: a yellow oil.
1H NMR (400 MHz): l 7.34–7.18 (m, 5H), 6.42 (d,
J=15.9 Hz, 1H), 6.19 (dt, J=15.9, 6.8 Hz, 1H), 2.55–
2.51 (m, 4H). IR (neat): 3018, 2931, 2106, 1639, 1492,
1373, 1325, 1147, 966, 744, 694, 496 cm−1.
4.6.8. 5-Methyl-6-phenyl-3-oxabicyclo[3.1.0]hexan-2-one
8h. An oil, 12% yield, [h]2D3 −61 (c 0.14, CHCl3) (38%
ee) (Table 4, entry 21).
4.6.9. 6-(2-Phenylethyl)-3-oxabicyclo[3.1.0]hexan-2-one
8i. 8i was obtained by SiO2 chromatography with hex-
ane/EtOAc (7:3) in 81% yield as an oil. [h]2D4 −10 (c 0.7,
1
CHCl3) (79% ee) (Table 4, entry 11). H NMR (400
MHz): l 7.31–7.16 (m, 5H), 4.26 (dd, J=9.3, 4.9 Hz,
1H), 4.16 (d, J=9.3 Hz, 1H), 2.83–2.69 (m, 2H), 1.94
(br-q, J=4.9 Hz, 1H), 1.86 (dd, J=5.8, 2.7 Hz, 1H),
1.76–1.59 (m, 2H), 1.24–1.17 (m, 1H). IR (KBr): 3033,
2964, 2922, 2856, 1770, 1452, 1373, 1174, 975, 754, 702,
626 cm−1. Anal. calcd for C13H14O2: C, 77.20; H, 6.98.
Found: C, 76.94; H, 7.05%.
4.6.10. 6,6-Diphenyl-3-oxabicyclo[3.1.0]hexan-2-one 8j.
8j was obtained by SiO2 chromatography with hexane/
EtOAc (7:3) in 35% yield as a colorless solid; mp
117°C, [h]2D3 +34 (c 0.5, CHCl3) (81% ee) (Table 4, entry
1
18). H NMR (400 MHz): l 7.44–7.14 (m, 10H), 4.48
(dd, J=10.0, 5.4 Hz, 1H), 4.23 (ddd, J=10.0, 1.0, 0.7
Hz, 1H), 2.95 (ddd, J=6.5, 5.4, 1.0 Hz, 1H), 2.81 (dd,
J=6.5, 0.7 Hz, 1H). IR (KBr): 3060, 3028, 2962, 2906,
1766, 1664, 1598, 1492, 1446, 1361, 1286, 1172, 1082,
1043, 981, 925, 881, 846, 759, 705, 665, 609, 547, 470
cm−1. Anal. calcd for C17H14O2: C, 81.58; H, 5.64.
Found: C, 81.47; H, 5.63%.
4.7.2. (5E)-1-Diazo-6,7,10-dimethylundec-5,9-dien-2-one
11b. Compound 11b was prepared in 45% yield from
geranyl bromide (2 g, 9.20 mmol) in the same proce-
1
dure as described for 11a. 11b: a yellow oil. H NMR
(400 MHz): l 5.24 (br-s, 1H), 5.08 (m, 2H), 2.33 (br-m,
4H), 2.06 (dt, J=7.6, 7.2 Hz, 2H), 1.98 (t, J=7.2 Hz,
2H), 1.67 (s, 3H), 1.61 (s, 3H), 1.59 (s, 3H). IR (KBr):
2966, 2922, 2854, 2104, 1641, 1444, 1375, 1321, 1259,
1141, 1109, 806 cm−1. HREIMS m/z, calcd for
C13H20N2O: 220.1576. Found: 220.1572.
4.6.11. 6-(1-Methylethyl)-3-oxabicyclo[3.1.0]hexan-2-one
8k8a. 8k was obtained by SiO2 chromatography with
hexane/EtOAc (7:3) in 34% yield as a colorless oil. [h]D23
−17 (c 0.175, CHCl3) (75% ee) (Table 4, entry 13).
Spectroscopic data (1H NMR and IR) of this sample
were identical with the reported ones.8a
4.7.3. 1-Diazo-6-methyl-5-hepten-2-one 11c30a. Com-
pound 11c was prepared in 47% yield from prenyl
bromide (1.22 g, 4.81 mmol) in the same procedure as
described for 11a. 11c: a yellow oil. 1H NMR (400
MHz) l 5.23 (br-s, 1H), 5.09 (t, J=6.2 Hz, 1H), 2.32
(pseud-s, 4H), 1.68 (s, 3H), 1.62 (s, 3H). IR (KBr):
3084, 2918, 2858, 2102, 1639, 1452, 1317, 1089, 1029,
983, 891, 859, 773, 638, 495 cm−1.
4.7. Synthesis of alkenyl diazomethyl ketones
4.7.1. (E)-1-Diazo-6-phenyl-5-hexen-2-one 11a29. NaH
(0.22 g, 5.5 mmol) was washed twice with hexane (2
mL) and dried under N2. Freshly distilled THF (14 mL)
was added to NaH under N2. The suspension was
cooled to 0°C and acetylacetone (0.5 mL, 5.5 mmol)
was added dropwise and stirred for 10 min. To this
solution was added a solution of n-BuLi (1.69 M, 3.25
mL, 5.25 mmol) in hexane and the resulting yellowish
orange solution was stirred at 0°C for an additional 20
min. To this solution was added a solution of cinnamyl
bromide (1.08 g, 5.5 mmol) in THF (2 mL) at 0°C and
the reaction mixture was slowly warmed to room tem-
perature with stirring. After 30 min, the reaction was
quenched with aqueous NH4Cl solution (5 mL).
Diethyl ether (10 mL) was added to the mixture and the
organic layer was separated. The aqueous layer was
extracted twice with Et2O (10 mL). The combined
4.7.4. (E)-1-Diazo-8-phenyloct-5-en-7-yn-2-one 11d.
Compound 11d was prepared in 47% yield from 5-
bromo-1-phenylbut-3-en-1-yne (0.35 g, 1.52 mmol) in
the same procedure as described for 11a. 11d: a yellow
1
oil. H NMR (400 MHz): l 7.34–7.31 (m, 2H), 7.30–
7.28 (m, 3H), 6.21 (dt, J=15.6, 7.7 Hz, 1H), 5.76 (d,
J=15.6, Hz, 1H), 5.26 (br-s, 1H), 2.51–2.44 (m, 4H).
IR (neat): 3018, 2925, 2106, 1638, 1488, 1373, 1325,
1166, 954, 758, 690, 528 cm−1. HREIMS m/z, calcd for
C14H12N2O (M+): 224.0950. Found: 224.0946.
4.7.5. (Z)-1-Diazo-6-phenyl-5-hexen-2-one 11e. Com-
pound 11e was prepared in 53% yield from (Z)-cin-
namyl bromide (1.08 g, 5.5 mmol) in the same

834
B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
1
procedure as described for 11a. 11e: a yellow oil. H
NMR (400 MHz): l 7.35–7.20 (m, 5H), 6.47 (d, J=11.1
Hz, 1H), 5.62 (dt, J=11.1, 6.6 Hz, 1H), 5.21 (br-s, 1H),
2.67 (ddd, J=15.1, 7.5, 1.7 Hz, 2H), 2.44 (br-s, 2H). IR
(neat): 3018, 2925, 2106, 1730, 1639, 1492, 1373, 1325,
1147, 966, 918, 769, 700 cm−1. HREIMS m/z, calcd for
C12H12N2O (M+−N2): 172.0888. Found: 172.0894.
4.7.8.
(E)-1-Diazo-7-(4-chlorophenyl)-6-hepten-2-one
13b. Compound 13b was prepared in 29% yield from
(E)-4-bromo-1-(4-chlorophenyl)-1-butene (2 g, 8.14
mmol) in the same procedure as described for 13a. 13b:
a yellow oil. 1H NMR (400 MHz): l 7.38–7.25 (m, 4H),
6.34 (d, J=15.6 Hz, 1H), 6.14 (dt, J=15.6, 7.2 Hz,
1H), 5.23 (br-s, 1H), 2.40 (br-s, 2H), 2.25 (dt, J=7.4,
7.2 Hz, 2H), 1.80 (tt, J=7.4, 7.2 Hz, 2H). IR (neat):
3105, 3026, 2933, 2102, 1639, 1490, 1373, 1321, 1091,
1010, 966, 846, 802, 678 cm−1. HREIMS m/z, calcd for
C13H13N2ClO (M+−N2): 220.0655. Found: 220.0659.
4.7.6. (E)-1-Diazo-5-methyl-6-phenyl-5-hexen-2-one 11f.
Compound 11f was prepared in 53% yield from (E)-3-
bromo-2-methyl-1-phenyl-1-propene (1.56 g, 7.39
mmol) in the same procedure as described for 11a. 11f:
a yellow oil. 1H NMR (400 MHz): l 7.33–7.29 (m, 2H),
7.22–7.17 (m, 3H), 6.29 (s, 1H), 5.28 (br-s, 1H), 2.51
(br-m, 4H), 1.87 (d, J=1.2 Hz, 3H). IR (neat): 2920,
2104, 1641, 1492, 1444, 1369, 1329, 1142, 1024, 918,
744, 700, 511 cm−1. HREIMS m/z, calcd for
C13H14N2O (M+−N2): 186.1045. Found: 186.1055.
4.7.9. (E)-1-Diazo-7-(4-methoxyphenyl)-6-hepten-2-one
13c. Compound 13c was prepared in 71% yield from
(E)-4-bromo-1-(4-methoxyphenyl)-1-butene (1.5 g, 6.21
mmol) in the same procedure as described for 13a. 13c:
1
a yellow solid, mp 53°C. H NMR (400 MHz): l 7.26
(d, J=8.8 Hz, 2H), 6.83 (d, J=8.8 Hz, 2H), 6.33 (d,
J=15.8 Hz, 1H), 6.01 (dt, J=15.8, 7.1 Hz, 1H), 5.23
(br-s, 1H), 3.79 (s, 3H), 2.36 (br-s, 2H), 2.24 (dt, J=7.3,
7.1 Hz, 2H), 1.80 (tt, J=7.5, 7.3 Hz, 2H). IR (KBr):
3091, 3003, 2933, 2904, 2835, 2100, 1637, 1604, 1510,
1458, 1384, 1303, 1176, 1149, 1107, 1028, 975, 806, 731,
553, 497 cm−1. Anal. calcd for C14H16N2O2: C, 68.83;
H, 6.60; N, 11.47. Found: C, 68.85; H, 6.57; N, 11.44%.
4.7.7.
(E)-1-Diazo-7-phenyl-6-hepten-2-one
13a31.
Freshly distilled THF (13 mL), diisopropylamine (1.84
mL, 13.26 mmol), and n-BuLi (1.69 M of hexane
solution, 8.2 mL, 13.26 mmol) were successively placed
in a 100 mL flask, cooled at −78°C, and stirred for 1 h
at the temperature. To this mixture was added acety-
lacetone (0.67 mL, 6.63 mmol) dropwise and stirred for
another 1 h at −78°C. To the solution, were successively
and slowly added a solution of (E)-4-bromo-1-phenyl-
1-butene (1.4 g, 6.63 mmol) in THF (2 mL) and N,N%-
dimethylpropyleneurea (13 mL) over 20 min, and the
mixture was further stirred for 6 h and quenched with
aqueous NH4Cl. Then, 20 mL of Et2O was added and
the organic layer was separated. The aqueous layer was
extracted twice with Et2O (10 mL). The combined
organic layers were washed with brine, dried over anhy-
drous MgSO4, and concentrated under reduced pres-
sure. The residue was chromatographed on silica gel
with hexane/EtOAc (19:1–12:1) to afford (E)-9-phenyl-
8-octene-2,4-dione in 56% yield.
4.7.10. (E)-1-Diazo-6-hepten-2-one 13d31. Compound
13d was prepared in 63% yield from 4-bromo-1-butene
(2 g, 14.81 mmol) in the same procedure as described
for 13a. 13d: a yellow oil. Spectroscopic data (1H NMR
and IR) of this sample were in agreement with the
reported ones.31
4.7.11. (E)-1-Diazo-7-phenyl-6-octen-2-one 13e. Com-
pound 13e was prepared in 43% yield from (E)-5-
bromo-2-phenyl-2-pentene (1.5 g, 6.63 mmol) in the
same procedure as described for 13a. 13e: a yellow oil.
1H NMR (400 MHz): l 7.38–7.20 (m, 5H), 5.73 (t,
J=7.1 Hz, 1H), 5.23 (br-s, 1H), 2.37 (br-s, 2H), 2.25
(dt, J=7.3, 7.1 Hz, 2H), 2.02 (s, 3H), 1.80 (tt, J=7.6,
7.3 Hz, 2H). IR (neat): 3026, 2931, 2100, 1641, 1492,
1444, 1373, 1143, 1107, 1080, 1024, 758, 698, 578, 462
cm−1. HREIMS m/z, calcd for C14H16N2O (M+−N2):
200.1201. Found: 200.1201.
(E)-9-Phenyl-8-octene-2,4-dione (0.61 g, 2.82 mmol)
was dissolved in acetonitrile (10 mL) and, to this solu-
tion, triethylamine (0.47 mL, 3.38 mmol) was added.
Then, a solution of methanesulfonyl azide (0.4 g, 3.38
mmol) in acetonitrile (1 mL) was added dropwise over
5 min with stirring. The resulting yellow solution was
further stirred for 4 h at room temperature to complete
diazo transfer. The reaction mixture was quenched with
aqueous NH4Cl (10 mL) and extracted twice with Et2O
(25 mL). The organic layer was concentrated in vacuo.
Aqueous NaOH solution (10%, 2 mL) was added to the
crude (E)-3-diazo-9-phenyl-8-octene-2,4-dione, stirred
for 30 min, diluted with water and extracted twice with
Et2O/EtOAc (3:1, 25 mL). The combined organic layers
were washed with brine and dried over anhydrous
MgSO4. The solvent was removed under reduced pres-
sure and the orange residue was chromatographed on
silica gel with hexane/EtOAc (10:1) to give 13a in 54%
yield. 13a: a yellow oil. 1H NMR spectrum of this
sample was identical with the reported ones.31
4.8. General procedure for intramolecular cyclopropa-
nation of 3-alkenyl diazomethyl ketones using (ON+
)Ru(II)(salen) complex 2 as the catalyst
(ON+)Ru(II)(salen) complex 2 4.9 mg, 5 mmol) was
dissolved in 4 mL of THF under N2. To this mixture
was added a THF solution (1 mL) of 3-alkenyl dia-
zomethyl ketone (0.1 mmol) dropwise over a period of
12 h using a syringe pump under irradiation of incan-
descent light. The reaction mixture was stirred for
another 4 h and concentrated in vacuo. The residue was
chromatographed on silica gel using hexane and ethyl
acetate (11:1) as eluent to yield the corresponding
[3.1.0]bicyclic ketone. The enantiomeric excess of the
product was determined as described in the footnotes of
Tables 5 and 6.

B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
835
4.8.1. 6-Phenylbicyclo[3.1.0]hexan-2-one 12a. Colorless
4.9. General procedure for intramolecular cyclopropa-
solid, mp 101°C. Yield: 78%, 94% ee, [h]2D2 −95 (c 0.275,
nation of 4-alkenyl diazomethyl ketones using (ON+)-
Ru(II)(salen) complex 4 as the catalyst
1
CHCl3) (Table 5, entry 3). H NMR (400 MHz): l 7.28
(dd, J=8.4, 7.1 Hz, 2H), 7.21 (d, J=8.4 Hz, 1H), 2.41
(comp, 2H), 2.32–2.11 (m, 4H). IR (KBr): 2935, 2873,
1712, 1658, 1599, 1494, 1458, 1404, 1296, 1267, 1219,
1191, 1072, 1036, 875, 798, 752, 700, 601, 522, 462
cm−1. Anal. calcd for C12H12O: C, 83.69; H, 7.02;
Found: C, 83.42; H, 7.04%.
(ON+)Ru(II)(salen) complex 4 (4.4 mg, 5 mmol) was
dissolved in 4 mL of THF under N2. To this mixture
was added a THF solution (1 mL) of 4-alkenyl dia-
zomethyl ketone (0.1 mmol) dropwise over a period of
12 h using a syringe pump under irradiation of incan-
descent light. The reaction mixture was stirred for
another 4 h and concentrated in vacuo. The residue was
chromatographed on silica gel using hexane and ethyl
acetate (11:1) as eluent to yield the corresponding
[4.1.0]bicyclic ketone. The enantiomeric excess of the
product was determined as described in the footnotes of
Table 7.
4.8.2.
6-Methyl-6-(4-methyl-3-penten-1-yl)bicyclo-
[3.1.0]hexan-2-one 12b. Colorless oil. Yield: 72%, 93%
ee, [h]2D4 +27 (c 0.46, CHCl3) (Table 6, entry 1). 1H
NMR (400 MHz) l 5.05 (tt, J=7.1, 1.5 Hz, 1H),
2.34–2.18 (m, 2H), 2.09–2.00 (m, 3H), 1.95–1.86 (m,
2H), 1.68 (comp, 4H), 1.60 (s, 3H), 1.33–1.20 (m, 2H),
1.14 (s, 3H). IR (KBr): 2935, 2858, 1720, 1652, 1600,
1494, 1296, 1267, 1190, 1078, 1026, 968, 875, 802 cm−1.
HREIMS m/z, calcd for C13H20O (M+): 192.1514.
Found: 192.1529.
4.9.1. 7-Phenylbicyclo[4.1.0]heptan-2-one 14a. Colorless
oil. Yield: 63%, 88% ee, [h]2D5 −87 (c 0.19, CHCl3)
1
(Table 7, entry 2). H NMR (400 MHz): l 7.27 (dd,
J=7.3, 7.1 Hz, 2H), 7.19 (d, J=7.3 Hz, 1H), 7.06 (d,
J=7.1 Hz, 2H), 2.66 (br-t, J=4.6 Hz, 1H), 2.39 (br-dt,
J=18.1, 4.8 Hz, 1H), 2.16 (ddd, J=17.6, 9.7, 7.5 Hz,
1H), 2.13–2.07 (m, 4H), 1.83–1.77 (m, 2H). IR (neat):
3030, 2931, 2858, 1685, 1602, 1494, 1452, 1338, 1244,
1166, 1068, 1028, 966, 900, 875, 744, 698, 520, 472, 430
cm−1. HREIMS m/z, calcd for C13H14O (M+): 186.1045.
Found: 186.1045.
4.8.3.
(1R,5S)-6,6-Dimethylbicyclo[3.1.0]hexan-2-one
12c32,33. Colorless oil. Yield: 65%, 87% ee, [h]2D4 +45 (c
0.2 CHCl3) (87% ee). Lit.32 [h]D23 −34.3 (c 1.0 CHCl3) for
1S,5R-isomer (63% ee) (Table 6, entry 2). 1H NMR
spectrum of this sample was in agreement with the
reported one.33b
4.9.2. 7-(4-Chlorophenyl)bicyclo[4.1.0]heptan-2-one 14b.
Colorless oil. Yield: 44%, 89% ee, [h]2D5 −83 (c 0.1,
4.8.4. 6-(2-Phenylethynyl)bicyclo[3.1.0]hexan-2-one 12d.
Colorless oil. Yield: 82%, 84% ee, [h]2D2 −121 (c 0.27,
1
CHCl3) (Table 7, entry 5). H NMR (400 MHz): l 7.24
1
CHCl3) (Table 6, entry 3). H NMR (400 MHz): l 7.37
(d, J=8.5 Hz, 2H), 7.00 (d, J=8.5 Hz, 2H), 2.62 (br-t,
J=4.4 Hz, 1H), 2.38 (br-dt, J=18.1, 4.7 Hz, 1H), 2.15
(ddd, J=17.6, 11.0, 6.5 Hz, 1H), 2.13–2.08 (m, 1H),
2.03–1.95 (m, 3H), 1.85–1.74 (m, 2H). IR (neat): 2923,
2895, 1681, 1492, 1342, 1245, 1164, 1089, 1066, 1012,
968, 875, 839, 787, 520, 414 cm−1. HREIMS m/z, calcd
for C13H13ClO (M+): 220.0654. Found: 220.0656.
(d, J=7.3 Hz, 2H), 7.30–7.26 (m, 3H), 2.42 (br-q,
J=4.5 Hz, 1H), 2.27–2.16 (m, 3H), 2.09 (dd, J=9.3, 1.0
Hz, 1H), 2.05 (dd, J=9.2, 8.3 Hz, 1H), 1.96 (dd,
J=3.7, 2.9 Hz, 1H). IR (neat): 2949, 1722, 1596, 1488,
1321, 1272, 1182, 1151, 1020, 869, 798, 760, 694, 530
cm−1. HREIMS m/z, calcd for C14H12O (M+): 196.0888.
Found: 196.0885.
4.9.3.
7-(4-Methoxyphenyl)bicyclo[4.1.0]heptan-2-one
14c. Colorless solid, mp 93°C. Yield: 72%, 77% ee, [h]D25
4.8.5. 6-Phenylbicyclo[3.1.0]hexan-2-one 12e. Colorless
oil. Yield: 62%, 79% ee, [h]2D2 +36 (c 0.28, CHCl3)
1
−93 (c 0.28, CHCl3) (Table 7, entry 6). H NMR (400
MHz): l 7.00 (d, J=8.5 Hz, 2H), 6.81 (d, J=8.5 Hz,
2H), 3.78 (s, 3H), 2.63 (br-t, J=3.6 Hz, 1H), 2.37
(br-dt, J=18.1, 4.7 Hz, 1H), 2.15 (ddd, J=18.3, 10.4,
7.3 Hz, 1H), 2.13–2.09 (m, 1H), 2.05–1.95 (m, 3H),
1.82–1.72 (m, 2H). IR (KBr): 2833, 1676, 1612, 1514,
1458, 1404, 1344, 1278, 1245, 1170, 1031, 964, 900, 877,
833, 785, 619, 532, 478 cm−1. Anal. calcd for C14H16O2:
C, 77.75; H, 7.46. Found: C, 77.47; H, 7.39%.
1
(Table 6, entry 4). H NMR (400 MHz): l 7.33–7.23
(m, 5H), 2.79 (dd, J=8.7, 8.0 Hz, 1H), 2.42 (ddd,
J=10.7, 8.0, 5.4 Hz, 1H), 2.29 (dd, J=9.3, 6.5 Hz, 1H),
2.26–2.17 (m, 1H), 1.96 (dd, J=13.4, 9.3 Hz, 1H), 1.86
(dd, J=19.0, 10.7 Hz, 1H), 0.926 (dd, J=19.0, 8.7 Hz,
1H); IR (neat): 2941, 2858, 1720, 1602, 1494, 1406,
1305, 1186, 933, 867, 779, 758, 702, 461 cm−1. HREIMS
m/z, calcd for C12H12O (M+): 172.0888. Found:
172.0888.
4.9.4. (1R,6S)-Bicyclo[4.1.0]heptan-2-one 14d34,35. Col-
orless oil. Yield: 46%, 33% ee, [h]2D5 +5 (c 0.2, CHCl3)
(Table 7, entry 7). Lit.35 [h]D25 +15.6 (c 3.7, CHCl3) (for
>99% ee, 1R,6S isomer). Spectroscopic data (1H NMR
and IR) of this sample were in agreement with the
reported ones.34
4.8.6. 5-Methy-6-phenylbicyclo[3.1.0]hexan-2-one 12f.
Colorless oil. Yield: 31%, 12% ee, [h]2D4 +3 (c 0.22,
CHCl3) (Table 6, entry 5). 1H NMR (400 MHz): l
7.32–7.23 (m, 3H), 7.14 (d, J=7.6 Hz, 2H), 2.59 (d,
J=3.2 Hz, 1H), 2.36–2.16 (m, 3H), 2.14 (d, J=3.2 Hz,
1H), 2.08–2.05 (m, 1H), 1.15 (s, 3H). IR (neat): 2927,
2872, 2384, 1714, 1485, 1452, 1414, 1252, 1175, 1068,
870, 843, 756, 704, 482 cm−1. HREIMS m/z, calcd for
C13H14O (M+): 186.1045. Found: 186.1046.
4.9.5. 7-Methyl-7-phenylbicyclo[4.1.0]heptan-2-one 14e.
Colorless oil. Yield: 36%, 5% ee. [h]2D4 +10 (c 0.1,
CHCl3) (Table 7, entry 8). 1H NMR (400 MHz): l
7.32–7.19 (m, 5H), 2.39 (br-d, J=17.3 Hz, 1H), 2.28–

836
B. Saha et al. / Tetrahedron: Asymmetry 14 (2003) 823–836
2.20 (m, 1H), 2.18–1.92 (m, 4H), 1.88–1.76 (m, 1H),
1.74–1.65 (m, 1H), 1.45 (s, 3H). IR (neat): 2925, 2854,
1689, 1494, 1446, 1327, 1240, 1147, 1026, 875, 765, 702
cm−1. HREIMS m/z, calcd for C14H16O (M+): 200.1201.
Found: 200.1201.
15. (a) Barberis, M.; Pe´rez-Prieto, J.; Stribia, S.-E.; Lahuerta,
P. Org. Lett. 2001, 3, 3317–3319; (b) Barberis, M.; Pe´rez-
Prieto, J.; Herbst, K.; Lahuerta, P. Organometallics 2002,
21, 1667–1673. Although the enantioselectivity of the
cyclopropanation giving bicyclo[3.1.0]hexan-2-one has
been reported to be 87% in Ref. 15a, it has been reported
to be 74% in Ref. 15b.
References
16. Katsuki, T. Adv. Synth. Catal. 2002, 34, 131–147.
17. For preliminary communication, see: (a) Saha, B.;
Uchida, T.; Katsuki, T. Synlett 2001, 114–116; (b)
Uchida, T.; Saha, B.; Katsuki, T. Tetrahedron Lett. 2001,
42, 2521–2524.
1. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds;
John Wiley & Sons: New York, 1998.
18. For preliminary communication, see: Saha, B.; Uchida,
T.; Katsuki, T. Chem. Lett. 2002, 846–847.
19. (a) Fukuda, T.; Katsuki, T. Synlett 1995, 825–826; (b)
Idem, Tetrahedron 1997, 53, 7201–7208.
20. Lorkovic, I. M.; Miranda, K. M.; Lee, B.; Bernhard, S.;
Schoonover, J. R.; Ford, P. C. J. Am. Chem. Soc. 1998,
120, 11674–11683.
21. Takeda, T.; Irie, R.; Katsuki, T. Synlett 1999, 1166–1168.
22. Doyle, M. P.; Winchester, W. R.; Hoorn, J. A. A.;
Lynch, V.; Simonsen, S. H. J. Am. Chem. Soc. 1993, 115,
9968–9978.
23. (a) Davies, H. M. L.; Bruzinski, P. R.; Lake, D. H.;
Kong, N.; Fall, M. J. J. Am. Chem. Soc. 1996, 118,
6897–6907; (b) Maxwell, J. L.; O’Malley, S.; Brown, K.
C.; Kodadek, T. Organometallics 1992, 11, 645–652; (c)
Doyle, M. P.; Zhou, Q.-L.; Raab, C. E.; Roos, G. H. P.;
Simonsen, S. H.; Lynch, V. Inorg. Chem. 1996, 35, 6064–
6073; (d) Doyle, M. P.; Kalinin, A. V. J. Org. Chem.
1996, 61, 2179–2184.
24. Addition of N-methylimidazole has been reported to
accelerate the reaction rate of Co-catalyzed cyclopropa-
nation and to enhance its stereoselectivity. (a) Yamada,
T.; Ikeno, T.; Sekino, H.; Sato, M. Chem. Lett. 1999,
719–720; (b) Ikeno, T.; Sato, M.; Yamada, T. Chem.
Lett. 1999, 1345–1346.
2. (a) Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998,
54, 7919–7946; (b) Pfaltz, A.; Lydon, K. M.; McKervey,
A. M.; Charette, A. B.; Level, H. Comprehensive Asym-
metric Catalysis; Jacobsen, E. N.; Pfaltz, A., Eds.;
Yamamoto, H. Springer, Berlin, 1999; Chapter 16.
3. (a) Niimi, T.; Uchida, T.; Irie, R.; Katsuki, T. Adv.
Synth. Catal. 2001, 343, 79–87; (b) Uchida, T.; Irie, R.;
Katsuki, T. Tetrahedron 2000, 56, 3501–3509.
4. (a) Doyle, M. P.; Peterson, C. S.; Parker, D. L., Jr.
Angew. Chem., Int. Ed. Engl. 1996, 35, 1334–1336; (b)
Tokunoh, R.; Tomiyama, H.; Sodeoka, M.; Shibasaki,
M. Tetrahedron Lett. 1996, 37, 2449–2452; (c) Mu¨ller, P.
C.; Bole´a, C. Synlett 2000, 826–828.
5. Pique, C.; Fahndrich, B.; Pfaltz, A. Synlett 1995, 491–
492.
6. Cho, D. J.; Jeon, S.-J.; Kim, H.-S.; Cho, C.-S.; Shim,
S.-C.; Kim, T.-J. Tetrahedron: Asymmetry 1999, 10,
3833–3848.
7. (a) Park, S.-B.; Murata, K.; Matsumoto, H.; Nishiyama,
H. Tetrahedron: Asymmetry 1995, 6, 2487–2494; (b)
Nishiyama, H.; Itoh, Y.; Sugawara, Y.; Matsumoto, H.;
Aoki, K.; Itoh, K. Bull. Chem. Soc. Jpn. 1995, 68,
1247–1262.
8. (a) 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, 5763–5765; (b) Doyle, M.
P.; Hu, W.; Chapman, B.; Marnett, A. B.; Peterson, C.
S.; Vitale, J. P.; Stanley, S. A. J. Am. Chem. Soc. 2000,
122, 5718–5728; (c) Doyle, M. P.; Davies, S. B.; Hu, W.
Org. Lett. 2000, 2, 1145–1147; (d) Martin, S. F.; Spaller,
M. R.; Liras, S.; Hartmann, B. J. Am. Chem. Soc. 1994,
116, 4493–4494; (e) Doyle, M. P.; Peterson, C. S.; Se,
Q.-L.; Nishiyama, H. J. Chem. Soc., Chem. Commun.
1997, 211–212.
25. Enantioselectivity of intermolecular cyclopropanation
catalyzed by complex 3 was also improved by the addi-
tion of N-methylimidazole (Ref. 3a).
26. Daniewski, A. R.; Wojceichowska, W. J. Org. Chem.
1982, 47, 2993–2995.
27. Anderson, K.; Kuruvilla, A.; Uretsky, N.; Miller, D. J.
Med. Chem. 1981, 24, 683–687.
28. Jung, M. E.; Angelica, S.; D’Amico, D. C. J. Org. Chem.
1997, 62, 9182–9187.
29. Fawzi, M. M.; Gutsche, C. D. J. Org. Chem. 1966, 47,
1390–1393.
30. (a) Julia, S.; Linstrumelle, G. Bull. Soc. Chim. Fr. 1966,
11, 3490–3498; (b) Mori, K.; Matsui, M. Tetrahedron
1969, 25, 5013–5018.
9. (a) Davies, H. M. L.; Brion, D. D. Tetrahedron Lett.
1996, 37, 3967–3970; (b) Davies, H. M. L.; Brion, D. D.
J. Org. Chem. 1999, 64, 8501–8508.
31. Allen, A. D.; Fenwick, M. F.; Henry-Riad, H.; Tidwell,
10. Munslow, I. J.; Gillespie, K. M.; Deeth, R. J.; Scott, P.
T. T. J. Org. Chem. 2001, 66, 5759–5765.
Chem. Commun. 2001, 1638–1639.
32. Kim, G.-S.; Cho, W.-C.; Ahn, H. K. Tetrahedron 1999,
55, 10079–10086.
11. Kim, G.-S.; Cho, W.-C.; Ahn, H. K. Tetrahedron 1999,
55, 10079–10086.
33. (a) Chapman, O. L.; Rettig, T. A.; Griswold, A. A.;
Dutton, A. I.; Fitton, P. Tetrahedron Lett. 1963, 4,
2049–2055; (b) Cruciani, G.; Margeretha, P. Helv. Chem.
Acta 1990, 73, 890–895.
34. Mash, E. A.; Nelson, K. A. Tetrahedron 1987, 43, 679–
692.
12. Park, W.-S.; Son, H.-J.; Kim, G.-S.; Ahn, H. K. Tetra-
hedron: Asymmetry 1999, 10, 1903–1911.
13. Che, C.-M.; Huang, J.-S.; Lee, F.-W.; Li, Y.; Lai, T.-S.;
Kwong, H.-L.; Teng, P.-F.; Lee, W.-S.; Lo, W.-C.; Peng,
S.-M.; Zhou, Z.-Y. J. Am. Chem. Soc. 2001, 123, 4119–
4129.
35. Mash, E. A.; Torok, D. S. J. Org. Chem. 1989, 54,
250–253.
14. Doyle, M. P.; Eismont, M. Y.; Zhou, Q. L. Russ. Chem.
Bull. 1997, 46, 955–958.