A convenient and efficient preparation of β-substituted α-haloenones from diazodicarbonyl compounds

Article abstract of DOI:10.1016/j.tet.2003.09.087

Rhodium(II)-catalyzed reactions of cyclic diazodicarbonyl compounds with a variety of halides have been examined. With acid halides, β-acyloxy α-haloenones are produced in good yields. With benzyl halides, β-benzyloxy α-haloenones are obtained in good yie

Full text of DOI:10.1016/j.tet.2003.09.087

Tetrahedron 59 (2003) 9333–9347
A convenient and efficient preparation of b-substituted
a-haloenones from diazodicarbonyl compounds
*
Yong Rok Lee, Bang Sub Cho and Hyuk Jin Kwon
School of Chemical Engineering and Technology, College of Engineering, Yeungnam University, Kyongsan 712-749, South Korea
Received 5 September 2003; revised 24 September 2003; accepted 25 September 2003
Abstract—Rhodium(II)-catalyzed reactions of cyclic diazodicarbonyl compounds with a variety of halides have been examined. With acid
halides, b-acyloxy a-haloenones are produced in good yields. With benzyl halides, b-benzyloxy a-haloenones are obtained in good yields.
Reactions with methylene halides yield b-halomethoxy a-haloenones in good yields, whereas reactions with ethyl halides and ethylene
dihalides result in b-hydroxy a-haloenones in high yields. These reactions provide a useful and rapid entry to b-substituted a-haloenones.
The mechanistic pathway for the formation of these products has been also described in terms of halonium ylides.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
the breadth and mechanism of the reactions described in our
1
2
preliminary communication, we have studied a number of
halides in reaction with metal carbenoids derived from
cyclic diazodicarbonyl compounds. We report herein a
facile and efficient preparation of a variety of a-haloenones
as a catalytic reaction starting from diazodicarbonyl
compounds.
The a-haloenones have been widely used as a key
1
intermediate in the synthesis of numerous compounds
2
and biologically active natural products. There are many
methods available for the preparation of a-haloenones.
They are typically prepared by treatment of a,b-enones with
3
4
halogenating agents such as X , NaX/oxone, NaX/DMD/
2
5
6
7
8
Amberlyst 15, PhSeX, pyr/HBr/Br , KBrO /HBr/H O
2
2
3
followed by dehydrohalogenation under acidic or basic
conditions. Although these reagents are known to be highly
reactive, their synthetic exploitation has been limited due to
the difficulty in controlling their regioselectivity, the strong
reaction conditions, and the side reactions involving
2. Results and discussion
Diazodicarbonyl compounds 1–7 were prepared by diazo-
transfer reaction of the corresponding 1,3-dicarbonyl
1
3
compounds with MsN (Fig. 1). These solid compounds
3
9
polyhalogenation. The necessity for overcoming these
are fairly stable and can be stored in a refrigerator for a long
time without any decomposition. We originally described
reaction of diazodicarbonyl compounds with acid chlorides
serious problems has prompted our research for a prep-
aration of b-substituted a-haloenones. In particular, a few
methods for preparation of b-alkyl a-haloenones have been
1
2a
in the presence of Rh (OAc) .
4
The influence of other
2
3
b,4
reported in the literature,
the direct preparation of acyloxy, benzyloxy, and halo-
but no facile methodology for
metal catalysts between diazodicarbonyl compound 1 and
acetyl chloride was first investigated. No products were seen
with copper acetate (1 mol%) at room temperature, while
methoxy a-haloenones has yet been developed.
both Rh (OCOCF )
2
(0.5 mol%) and Rh (OAc)
2 4
3 4
The rhodium(II)-catalyzed decomposition of diazodi-
carbonyl compounds has become a useful method in
(0.5 mol%) gave product 8 in 13 and 64% yields,
respectively. We found that electron-rich rhodium catalyst
1
0
organic synthesis. We have been interested in rhodium-
II)-catalyzed reactions of diazodicarbonyl compounds with
(
1
1
several substrates. While continuing our work based on
the rhodium(II)-catalyzed reactions, we have expanded this
work to the synthesis of a-haloenones. In order to examine
Keywords: rhodium(II)-catalyzed reaction; diazodicarbonyl compounds;
beta-acyloxy alpha-haloenones; beta-benzyloxy alpha-haloenones; beta-
halomethoxy alpha-haloenones; beta-hydroxy alpha-haloenones.
*
Corresponding author. Tel.: þ82-538102529; fax: þ82-538148790;
e-mail: yrlee@yu.ac.kr
Figure 1.
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.09.087

9334
Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
Table 1. Effect of catalyst in the reaction of diazodicarbonyl compound 1
and acetyl chloride
showed a much superior catalytic activity for this reaction.
A higher yield of 8 (81%) was obtained when 1 mol% of
Rh (OAc) was used as a catalyst. The structure of 8 is
2
4
easily assigned by the two IR carbonyl absorptions at 1777
2
1
and 1693 cm associated with a vinyl ester and an enone.
1
The H NMR spectrum shows the peak of the methyl group
of the vinyl acetate at d 2.26 ppm as a singlet. Further
1
3
support is obtained from its C NMR spectrum, which
shows the expected two carbonyl carbons of the enone at d
Catalyst
Condition (mol%)
Yield (%)
191.31 and the vinyl ester at d 166.15 (Table 1).
Cu (OAc)
2
1
0
Rh
Rh
Rh
2
2
2
(OCOCF
3
)
4
0.5
0.5
1
13
64
81
Additional reaction of diazodicarbonyl compound 1 with
other acid chlorides such as propionyl chloride and butyryl
chloride (20-fold excess), which serve as a reactant and a
solvent, in the presence of 1 mol% of Rh (OAc) , afforded
(OAc)
(OAc)
4
4
2
4
a
Table 2. Reaction of diazodicarbonyl compounds with acid halides
b
Entry Diazodicarbonyl compound Acid halide
Condition
rt, 12 h
Product
Yield (%)
1
85
2
3
rt, 12 h
96
89
508C, 7 h
4
508C, 7 h
80
5
6
7
8
rt, 12 h
rt, 12 h
rt, 12 h
rt, 12 h
80
90
92
71
9
rt, 12 h
70

Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
9335
Table 2 (continued)
Entry Diazodicarbonyl compound
b
Acid halide
Condition
Product
Yield (%)
c
1
1
0
1
508C, 7 h
70
c
508C, 7 h
75
12
508C, 7 h
70
13
508C, 7 h
72
1
1
1
4
5
6
rt, 12 h
rt, 12 h
rt, 12 h
70
74
74
17
508C, 7 h
53
18
rt, 12 h
46
a
b
c
Reactions were carried out in the presence of 1 mol% of Rh
Isolated yields after column chromatography.
Reaction of entries 10 and 11 was carried out in the presence of 1 mol% of Rh
2 4
(OAc) .
2
4
(OPiv) .

9336
Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
Scheme 1.
compounds 9–10 in 85 and 96% yields, respectively
entries 1 and 2, Table 2). Reaction of diazodicarbonyl
(
compounds 3–4 with a phenyl and a furyl group on the
cyclic ring gave products 11–12 in 89 and 80% yields
(entries 3 and 4), respectively. Interestingly, reaction of
diazodicarbonyl compound 4 with phenylacetyl chloride
and crotonyl chloride afforded products 16–17 in 71 and
70% yields, respectively (entries 8 and 9). In these reactions,
Scheme 2.
a
Table 3. Reaction of diazodicarbonyl compounds with benzyl halides
b
Entry
Diazodicarbonyl compound
Benzyl halide
Condition
rt, 12 h
Product
Yield (%)
1
81
2
3
rt, 12 h
69
81
rt, 12 h
4
rt, 9 h
93
5
6
rt, 12 h
78
66
rt, 12 h

Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
9337
Table 3 (continued)
Entry Diazodicarbonyl compound
b
Benzyl halide
Condition
Product
Yield (%)
7
rt, 9 h
95
c
8
508C, 6 h
55
9
rt, 10 h
rt, 12 h
rt, 10 h
67
55
65
1
1
1
0
1
2
rt, 10 h
70
c
13
508C, 6 h
60
14
rt, 12 h
85
a
b
c
Reaction were carried out in the presence of 1 mol% of Rh
Isolated yields after column chromatography.
Reaction of entries 8 and 13 was carried out in the presence of 1 mol% of Rh
2 4
(OAc) .
2
4
(OPiv) .

9338
Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
1
2b
no addition products to the aromatic ring and CvC bond
could be detected.
a-haloenones. Reaction of 7 with benzyl chloride in the
presence of 1 mol% of Rh (OAc) at room temperature for
2
4
12 h afforded 3-benzyloxy-2-chlorophenalen-1-one (32) in
Reactions of more complex diazodicarbonyl compounds
such as 3-diazo-2,4-chromenedione (5), 3-diazoquinoline-
2,4-dione (6), and 2-diazo-1H-1,3-phenalenedione (7) were
also successful. Treatment of 5 with acetyl chloride and
propionyl chloride at room temperature for 12 h under
an 82% yield (Scheme 2). The formation of 32 is identified
by the observation of a carbonyl absorption in the IR
spectrum at 1647 cm2 (enone CvO) and the expected
chemical shifts associated with the methylene protons of the
benzyl group as a singlet at d 5.40 ppm. Further reactions of
diazodicarbonyl compounds with a range of benzyl halides
were next examined under rhodium catalysis. Treatment of
1 with benzyl chloride afforded expected product 33 in 81%
yield (entry 1, Table 3). In the treatment of benzyl chlorides
with methyl substituents on the aromatic ring such as 3- and
4-methylbenzyl chloride, the expected products 34 and 35
were obtained in 69 and 81% yields, respectively (entries 2
and 3, Table 3). In particular, reactions with 4-methoxy-
benzyl chloride afforded a-chloroenones 36 (93%) and 39
(95%) in high yields, respectively (entries 4 and 7).
1
1
3
mol% of Rh (OAc) afforded compounds 18–19 in 35 and
2 4
9% yields, respectively, whereas reaction at 508C for 7 h in
the presence of 1 mol% of Rh (OPiv) gave 18–19 in high
2
4
yields (70 and 75%). Similarly, reactions of 6 with
propionyl chloride and butyryl chloride at 508C for 7 h in
the presence of Rh (OAc) afforded products 20 and 21 in
2
4
7
0 and 72% yields, respectively. In these cases, only a single
product was seen and no other possible regioisomers were
found (entries 10–13, Table 2). Reaction of 7 with acetyl
chloride, propionyl chloride, and butyryl chloride afforded
products 22–24 in 70–74% yields (entries 14–16).
When benzyl bromide was used as a a-halogenating
reagent, expected bromoenones were produced in good
yields (entry 9–14, Table 3). Reaction of 1 with benzyl
bromide in the presence of 1 mol% of Rh (OAc) afforded
Extension of the reaction with AcBr was also successful.
Reaction of 6 with AcBr at 508C for 7 h afforded
bromoenone 25 in 53% yield (entry 17). Similarly, reaction
of diazodicarbonyl compound 7 with AcBr at room
temperature for 12 h gave the expected product 26 in 46%
yield (entry 18). The results are summarized in Table 2.
2
4
3-benzyloxy-2-bromocyclohex-2-enone (41) in 67% yield.
With methyl substituted benzyl bromide, reactions were
also successful. Reactions with 2-methylbenzyl bromide
afforded 42 in 55% yield, whereas reaction with 4-methyl-
benzyl bromide gave 43 in 65% yield (entries 10 and 11).
Reactions of the more complex diazodicarbonyl compounds
5 and 7 were also successful. Treatment of 5 with benzyl
bromide at 508C for 6 h in the presence 1 mol% of
Rh (OPiv) afforded 45 in 60% yield, whereas reaction of
Although the exact mechanism for the formation of 8 is not
clear, it is best described as shown in Scheme 1. The
diazodicarbonyl compound 1 first gives a metal carbenoid
27 by displacement of nitrogen by Rh (OAc) . Nucleophilic
2 4
attack of the chlorine or oxygen atom in the acid chloride to
2
4
the electrophilic carbenoid 27 yields two possible inter-
15
mediates 28 (halonium ylide) and 30 (carbonyl ylide).
However, only compound 8 was observed experimentally,
with no formation of the other possible product 31 being
observed. Therefore, nucleophilic attack of the chlorine on
7 with benzyl bromide at room temperature for 12 h gave 46
in 85% yield (entries 13 and 14). The results are
summarized in Table 3.
1
4
The plausible mechanism for the formation of 32 is shown
in Scheme 3. The diazodicarbonyl compound 7 first gives a
metal carbenoid 47, which is attacked by the chlorine atom
of benzyl chloride to give 48. The intermediate 48
undergoes the intramolecular substitution reaction to yield
product 32.
2
7 gives intermediate 28, which undergoes fast intra-
molecular nucleophilic addition of oxygen to the carbonyl
group followed by the cleavage of the C–Cl bond to give
product 8.
We also reported the reactions of diazodicarbonyl
compounds with benzyl halides to produce b-benzyloxy
Next, in order to obtain other types of a-halo compounds,
Scheme 3.
reactions of diazodicarbonyl compounds with alkyl halides
such as methylene chloride or methylene bromide were
attempted using a rhodium catalyst. Methylene chloride was
first used as a test substrate to screen the new halogenating
agents. Treatment of 7 with methylene chloride as a reactant
and a solvent in the presence of 0.5 mol% of Rh (OAc) at
2
4
room temperature for 10 h affords the 2-chloro-3-chloro-
methoxyphenalen-1-one (49) in 81% yield (Scheme 4).
Support for the structural assignment comes from its
Scheme 4.

Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
9339
a
Table 4. Reaction of diazodicarbonyl compounds with methylene halides
b
Entry Diazodicarbonyl compound Methyle halide
Condition
rt, 4 h
Product
Yield (%)
1
CH Cl
2
2
79
90
2
CH Cl
2
2
rt, 5 h
3
4
CH Cl
2
2
rt, 5 h
81
75
CD Cl
2
2
rt, 7 h
5
6
CH
CH
CH
2
Br
2
Br
2
Br
2
2
2
rt, 5 h
75
78
85
rt, 5 h
7
508C, 5 h
a
Reactions were carried out in the presence of 1 mol% of Rh
Isolated yields after column chromatography.
2 4
(OAc) .
b
spectroscopic analysis. The formation of 49 was easily
assigned by the chemical shifts associated with the
methylene protons of the chloromethoxy group at d
Additional reaction of diazodicarbonyl compounds with
methylene halides was also successful. Interestingly,
reaction of 4 with CD Cl afforded the product 53 in
2
2
6
.19 ppm as a singlet and by its IR carbonyl absorption of
75% yield (entry 4, Table 4). In this case, no peaks of
1
the methylene group in the H NMR spectrum could
21
the enone at 1657 cm . Similarly, reaction of diazodi-
carbonyl compound 1 with methylene chloride afforded
expected compound 50 in 79% yield (entry 1, Table 4).
Surprisingly, our result is in clear contrast to the rhodium
be detected, due to a change of deuterium. Treatment of
2 with methylene bromide at room temperature for 5 h
in the presence of 0.5 mol% of Rh (OAc) gave 54 in
2
4
(
gave exclusively 2-chloro-1,3-cyclohexanedione.
II)-catalyzed reaction of 1 with methylene chloride which
1
75% yield. Similarly, other bromoenones 55 and 56
were produced in 78 and 85% yields, respectively
6
Scheme 5.

9340
Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
1
scopic analysis. The H NMR spectrum shows the peak of
the enol proton at d 6.52 ppm as a broad singlet.
Interestingly, we found that the product from this reaction
was very different from that with methylene halides as
already shown in Scheme 4. A number of other alkyl
halides were tested in the reaction (Table 5) as a new
a-halogenating reagent. Reaction of 1 with ethylene
dichloride also afforded product 58 in a 95% yield (entry
1, Table 5). As other a-brominating reagents, ethyl bromide,
ethylene dibromide, and 1,3-dibromopropane afforded
b-hydroxy a-bromoenone 59 in 95, 96, and 98% yields,
respectively (entries 2–4). Although a few methods
available for the synthesis of b-hydroxy a-chloro and
Scheme 6.
(entries 6 and 7). The results are summarized in
Table 4.
The formation of 49 can be explained in terms of a
nucleophilic attack by the chlorine of methylene chloride as
shown in Scheme 5. Electrophilic carbenoid 47 is attacked
by chlorine to give an ylide 57, which subsequently
undergoes an intramolecular substitution reaction to give
product 49.
8
a-bromoenone have been reported, there are no known
examples for the preparation of b-hydroxy a-iodoenones.
Under the same conditions, reaction with ethyl iodide and
propyl iodide yielded b-hydroxy a-iodoenone 60 in 94 and
96% yields, respectively (entries 5 and 6). The other similar
results are collected in Table 5 (entries 7–14).
In order to extend the utility of this methodology, further
reactions with other alkyl halides such as n-butyl chloride,
ethyl bromide, and ethyl iodide were next examined. When
diazodicarbonyl compound 1 was treated with n-butyl
chloride as a reagent and a solvent at room temperature for
The formation of 58 could be explained as shown in
Scheme 7. Unlike methylene chloride, n-butyl chloride has
hydrogens on the b-carbon. Nucleophilic attack of chlorine
of n-butyl chloride to the electrophilic metal carbenoid 27
gives the chloronium ylide 66, which undergoes a hydrogen
abstract and cleavage of the C–Cl bond to yield 58. In view
of our results, with alkyl halides that have no b-hydrogens
such as methylene chloride and methylene bromide,
b-substituted a-haloenone products are formed, while
1
0 h in the presence of 0.5 mol% of Rh (OAc) , b-hydroxy
2 4
a-chloroenone 58 was obtained in a high yield (96%)
instead of the formation of b-substituted a-chloroenone
(
Scheme 6).
The structure of 58 was easily determined by its spectro-
a
Table 5. Reaction of diazodicarbonyl compounds with alkyl halides
a
b
Entry
Diazodicarbonyl compound
Alkyl halide
Product
Yield (%)
1
2
3
4
5
6
ClCH
3
CH CH
BrCH
BrCH
2
CH Cl
2
58 X¼Cl
95
95
96
98
94
96
2
Br
59 X¼Br
59 X¼Br
59 X¼Br
60 X¼l
2
CH
CH
2
Br
CH Br
2
2
2
CH
CH
3
CH
CH
2
l
3
2
CH
2
l
60 X¼l
7
8
CH
CH
3
CH
CH
2
CH
Br
2
CH
2
Cl
61 X¼Cl
62 X¼Br
92
90
3
2
9
CH
3
CH CH
2
2
CH
2
Cl
63 X¼Cl
63 X¼Cl
64 X¼Br
64 X¼Br
65 X¼l
98
98
98
96
93
92
10
11
12
13
14
ClCH
CH CH
BrCH CH
CH CH
lCH CH
2
2
CH Cl
3
2
Br
2
2
Br
3
2
l
2
2
CH
2
l
65 X¼l
a
Reactions run with 0.5 mol% of Rh
Isolated yields after column chromatography.
2
(OAc)
4
at room temperature for 10 h.
b

Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
9341
Scheme 7.
1
alkyl halides with b-hydrogens such as n-butyl chloride, ethyl
bromide, and ethyl iodide lead to b-hydroxy a-chloroenones.
(172 mg, 85%) as a liquid: H NMR (300 MHz, CDCl ) d
3
2.64 (2H, t, J¼6.1 Hz, CH ), 2.57–2.48 (4H, m, 2£CH ),
2
2
3
1
2
.07–1.99 (2H, m, CH ), 1.19 (3H, t, J¼6.0 Hz, CH );
C
NMR (75 MHz, CDCl ) d 191.33 (CvO, enone), 169.78
2
3
In conclusion, rhodium-catalyzed reactions of diazodi-
carbonyl compounds with a variety of alkyl halides are
described. This reaction provides an efficient synthetic route
for the preparation of a-halo enones. Further application of
these products will be investigated, which is now in progress
in our laboratory.
3
(CvO, ester), 164.49, 121.85, 37.23, 29.91, 27.42, 20.15,
8.75; IR (neat) 2946, 2888, 1770 (CvO, vinylic ester), 1694
(CvO, enone), 1628, 1460, 1424, 1345, 1277, 1167, 1115,
1076, 1017, 986, 841 cm2 . Anal. calcd for C H ClO : C,
1
9
11
3
53.35; H, 5.47. Found: C, 53.22; H, 5.54.
3
.1.3. 3-Butanoyloxy-2-chlorocyclohex-2-enone (10).
Reaction of 1 (138 mg, 1.0 mmol) and butyryl chloride
2.131 g, 20.0 mmol) under Rh (OAc) (4.4 mg) afforded
3
. Experimental
(
2
4
1
All experiments were carried out under a nitrogen
atmosphere. Merck precoated silica gel plates (Art. 5554)
with fluorescent indicator were used for analytical TLC.
Flash column chromatography was performed using silica
gel 9385 (Merck). Melting points were determined with
microcover glasses on a Fisher–Johns apparatus and are
10 (208 mg, 96%) as a liquid: H NMR (300 MHz, CDCl )
3
d 2.67 (2H, t, J¼6.1 Hz, CH ), 2.59 (2H, t, J¼6.3 Hz, CH ),
2
2
2.50 (2H, t, J¼7.4 Hz, CH ), 2.11–2.02 (2H, m, CH ),
2
2
1
3
1.80–1.64 (2H, m, CH ), 1.00 (3H, t, J¼7.4 Hz, CH );
C
NMR (75 MHz, CDCl ) d 191.54 (CvO, enone), 168.95
2
3
3
(CvO, ester), 164.59, 121.77, 37.14, 35.69, 29.85, 20.27,
18.05, 13.35; IR (neat) 2967, 2878, 1769 (CvO, vinylic
ester), 1696 (CvO, enone), 1628, 1458, 1418, 1346, 1275,
1235, 1127, 1088, 1015, 970, 914 cm2 . Anal. calcd for
C H ClO : C, 55.44; H, 6.05. Found: C, 55.28; H, 5.96.
1
uncorrected. H NMR spectra were recorded on a Bruker
1
3
Model ARX (300 MHz) spectrometer. C NMR spectra
were recorded on a Bruker Model ARX (75 MHz)
spectrometer in CDCl3 using 77.0 ppm as the solvent
chemical shift. IR spectra were recorded on a JASCO FTIR
1
10
13
3
5
300 spectrophotometer. Elemental analyses and HRMS
3.1.4. 3-Acetoxy-2-chloro-5-phenylcyclohex-2-enone
(11). Reaction of 2 (214 mg, 1.0 mmol) and acetyl chloride
(1.570 g, 20.0 mmol) under Rh (OAc) (4.4 mg) afforded
mass spectra were carried out by Korea Basic Science
Institute (Daegu).
2
4
1
11 (236 mg, 89%) as a liquid: H NMR (300 MHz, CDCl )
d 7.36–7.21 (5H, m, ArH), 3.55–3.43 (1H, m, CH), 3.07–
3
3.1. General procedure for the synthesis of a-acyloxy
a-haloenones (8–26)
1
3
2.75 (4H, m, 2£CH ), 2.08 (3H, s, CH ); C NMR
(75 MHz, CDCl ) d 190.51 (CvO, enone), 166.25 (CvO,
3
2
3
To a solution of diazodicarbonyl compound (1.0 mmol) and
acid halide (20 mmol) was added rhodium catalyst
vinylic ester), 163.24, 141.08, 128.91, 127.47, 126.52,
122.05, 44.13, 38.49, 37.43, 20.65; IR (neat) 3032, 2928,
1777 (CvO, vinylic ester), 1694 (CvO, enone), 1632,
(
0.01 mmol) at room temperature under a N atmosphere.
2
1427, 1372, 1244, 1169, 1044, 1019, 976, 914, 877 cm2
1
.
The reaction mixture was stirred at room temperature for
2 h or 508C for 7 h. The halide was evaporated under
1
Anal. calcd for C H ClO : C, 63.52; H, 4.95. Found: C,
14 13 3
reduced pressure to give the residue. The residue was
purified by flash column chromatography on silica gel to
give the product.
63.77; H, 5.03.
3.1.5. 3-Acetoxy-2-chloro-5-(2-furyl)-cyclohex-2-enone
12). Reaction of 3 (204 mg, 1.0 mmol) and acetyl chloride
(1.570 g, 20.0 mmol) under Rh (OAc) (4.4 mg) afforded
(
3.1.1. 3-Acetoxy-2-chlorocyclohex-2-enone (8). Reaction
of 1 (138 mg, 1.0 mmol) and acetyl chloride (1.570 g,
2
4
1
12 (204 mg, 80%) as a liquid: H NMR (300 MHz, CDCl )
3
2
8
0.0 mmol) under Rh (OAc) (4.4 mg) afforded 8 (153 mg,
2
1%) as a liquid: H NMR (300 MHz, CDCl ) d 2.67 (2H, t,
3
d 7.32 (1H, d, J¼1.8 Hz, CH), 6.28 (1H, dd, J¼3.3, 1.8 Hz,
4
1
CH), 6.07 (1H, d, J¼3.3 Hz, CH), 3.62–3.52 (1H, m),
13
J¼6.1 Hz, CH ), 2.59 (2H, t, J¼6.1 Hz, CH ), 2.26 (3H, s,
2.98–2.89 (3H, m), 2.84–2.75 (1H, m), 2.27 (3H, s, CH );
3
2
2
1
3
CH ), 2.11–2.02 (2H, m, CH ); C NMR (75 MHz,
3
C NMR (75 MHz, CDCl ) d 190.00 (CvO, enone),
2
3
CDCl ) d 191.31 (CvO, enone), 166.15 (CvO, vinylic
3
ester), 164.31, 121.97, 37.21, 29.84, 20.58, 20.13; IR (neat)
166.25 (CvO, vinylic ester), 162.54, 154.11, 141.92,
122.06, 110.25, 105.43, 41.50, 34.64, 31.92, 20.66; IR
(neat) 3121, 2917, 2849, 1777 (CvO, vinylic ester), 1696
(CvO, enone), 1632, 1508, 1429, 1364, 1169, 1017, 978,
2
1
8
4
959, 1777 (CvO, vinylic ester), 1693 (CvO, enone),
630, 1427, 1371, 1352, 1281, 1169, 1065, 1007, 968, 912,
73, 845 cm2 . Anal. calcd for C H ClO : C, 50.94; H,
1
21
943 cm . Anal. calcd for C H ClO : C, 56.60; H, 4.35.
12 11
8
9
3
4
.81. Found: C, 50.82; H, 5.14.
Found: C, 56.89; H, 4.57.
3
.1.2. 2-Chloro-3-propanoyloxycyclohex-2-enone (9).
3.1.6. 3-Acetoxy-2-chloro-5,5-dimethylcyclohex-2-enone
(13). Reaction of 4 (166 mg, 1.0 mmol) and acetyl chloride
(1.570 mg, 20.0 mmol) under Rh (OAc) (4.4 mg) afforded
Reaction of 1 (138 mg, 1.0 mmol) and propionyl chloride
1.850 g, 20.0 mmol) under Rh (OAc) (4.4 mg) afforded 9
(
2
4
2
4

9342
Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
1
13
13 (173 mg, 80%) as a liquid: H NMR (300 MHz, CDCl )
d 2.54 (2H, s, CH ), 2.44 (2H, s, CH ), 2.25 (3H, s, CH ),
2£CH ); C NMR (75 MHz, CDCl ) d 191.36 (CvO,
3
3
3
enone), 162.78 (CvO, ester), 161.59, 149.23, 120.94,
120.52, 51.00, 43.34, 32.58, 27.84, 18.29; IR (KBr) 2962,
2878, 1741 (CvO, vinylic ester), 1694 (CvO, enone),
1653, 1626, 1460, 1443, 1372, 1343, 1314, 1296, 1283,
1196, 1150, 1098, 1026, 1009, 970, 945 cm2 . Anal. calcd
for C H ClO : C, 59.39; H, 6.23. Found: C, 59.16; H,
2
2
3
1
3
1
.10 (6H, s, 2£CH ); C NMR (75 MHz, CDCl ) d 191.41
3
3
(
1
2
CvO, enone), 166.39 (CvO, vinylic ester), 162.54,
21.24, 51.05, 43.53, 32.62, 28.10, 29.93, 20.69; IR (neat)
963, 2876, 1777 (CvO, vinylic ester), 1694 (CvO,
1
enone), 1634, 1470, 1416, 1372, 1348, 1294, 1181, 1026,
1
1
2
15
3
þ
9
47, 920, 856 cm2 ; m/z (EI) 216 (M , 5%), 174 (96), 159
6.32.
(
68), 149 (49), 129 (19), 118 (100), 103 (120), 83 (22), 69
6), 55 (16). Anal. calcd for C H ClO : C, 55.44; H, 6.05.
Found: C, 55.43; H, 6.24.
(
3.1.11. 4-Acetoxy-3-chlorochromen-2-one (18). Reaction
of 5 (188 mg, 1.0 mmol) and acetyl chloride (1.570 g,
1
0
13
3
20.0 mmol) under Rh (OPiv) (6.1 mg) afforded 18
(167 mg, 70%) as a solid; mp 167–1688C (from hexane–
ethylacetate); H NMR (300 MHz, CDCl ) d 7.59 (1H, dd,
3
2 4
3
2
.1.7. 2-Chloro-5,5,-dimethyl-3-propanoyloxycyclohex-
-enone (14). Reaction of 4 (166 mg, 1.0 mmol) and
1
propionyl chloride (1.850 g, 20.0 mmol) under Rh (OAc)
2
J¼8.2, 7.5 Hz, ArH), 7.49 (1H, d, J¼7.8 Hz, ArH), 7.39
4
1
(
(
4.4 mg) afforded 14 (208 mg, 90%) as a liquid: H NMR
300 MHz, CDCl ) d 2.50 (2H, J¼6.0 Hz, CH ), 2.50 (2H, s,
(1H, d, J¼8.2 Hz, ArH), 7.34 (1H, dd, J¼7.8, 7.5 Hz, ArH),
1
3
2.49 (3H, s, CH ); C NMR (75 MHz, CDCl ) d 165.30
3
3
2
3
CH ), 2.41 (2H, s, CH ), 1.17 (3H, t, J¼6.0 Hz, CH ), 1.06
(CvO, ester), 157.75 (CvO, ester), 155.02, 151.17,
132.75, 125.00, 122.63, 116.85, 115.91, 20.34; IR (KBr)
3109, 3071, 3045, 1784 (CvO, vinylic ester), 1730 (CvO,
ester), 1620, 1566, 1493, 1453, 1356, 1281, 1200, 1173,
2
2
3
1
3
(
(
6H, s, 2£CH ); C NMR (75 MHz, CDCl ) d 191.37
3
3
CvO, enone), 169.99 (CvO, vinylic ester), 162.73,
1
2
21.03, 50.98, 43.46, 32.55, 27.84, 27.38, 8.73; IR (neat)
962, 2878, 1771 (CvO, vinylic ester), 1694 (CvO,
21
1138, 1090, 1038, 1015, 1001, 903, 777, 734 cm ; m/z (EI)
238 (M , 17%), 196 (100), 162 (9), 121 (71), 92 (13), 63 (6).
þ
HRMS calcd for C H ClO (M ) 238.0033. Found
238.0034.
enone), 1634, 1464, 1372, 1345, 1290, 1267, 1155, 1113,
1
C H ClO : C, 57.27; H, 6.55. Found: C, 57.54; H, 6.44.
074, 1026, 947, 918, 850 cm2 . Anal. calcd for
1
þ
1
1
7
4
1
1
15
3
3.1.8. 3-Butanoyloxy-2-chloro-5,5-dimethylcyclohex-2-
enone (15). Reaction of 4 (166 mg, 1.0 mmol) and butyryl
3.1.12. 3-Chloro-4-propanoyloxychromen-2-one (19).
Reaction of 5 (188 mg, 1.0 mmol) and propionyl chloride
(1.850 g, 20.0 mmol) under Rh (OPiv) (6.1 mg) afforded
chloride (2.131 g, 20.0 mmol) under Rh (OAc) (4.4 mg)
2
4
2
4
1
afforded 15 (224 mg, 92%) as a liquid: H NMR (300 MHz,
CDCl ) d 2.54 (2H, s, CH ), 2.49 (2H, t, J¼7.4 Hz, CH ),
19 (189 mg, 75%) as a solid; mp 1128C (from hexane–
1
ethylacetate); H NMR (300 MHz, CDCl ) d 7.59 (1H, dd,
3
3
2
2
2
2
.45 (2H, s, CH ), 1.77–1.70 (2H, m, CH ), 1.11 (6H, s,
2
J¼8.2, 7.5 Hz, ArH), 7.48 (1H, d, J¼7.8 Hz, ArH), 7.39
(1H, d, J¼8.2 Hz ArH), 7.33 (1H, dd, J¼7.8, 7.5 Hz ArH),
2.79 (2H, q, J¼7.6 Hz, CH ), 1.37 (3H, t, J¼7.6 Hz, CH );
2
1
3
£CH ), 1.00 (3H, t, J¼7.4 Hz, CH ); C NMR (75 MHz,
3
3
CDCl ) d 191.11 (CvO, enone), 166.20 (CvO, ester),
3
2
3
1
3
1
2
62.47, 121.11, 51.00, 43.44, 32.49, 27.81, 20.53; IR (neat)
965, 2878, 1769 (CvO, vinylic ester), 1696 (CvO,
C NMR (75 MHz, CDCl ) d 169.94 (CvO, ester), 157.84
3
(CvO, ester), 155.17, 151.21, 132.80, 124.99, 122.63,
116.90, 116.07, 27.33, 8.95; IR (KBr) 3046, 2948, 1780
(CvO, vinylic ester), 1730 (CvO, ester), 1618, 1566,
enone), 1634, 1468, 1415, 1372, 1346, 1289, 1155, 1127,
2
1
1
086, 1026, 947 cm . Anal. calcd for C H ClO : C,
12 17 3
21
5
8.90; H, 7.00. Found: C, 58.68; H, 7.23.
1451, 1348, 1283, 1262, 1105, 1065, 1015, 877 cm ; m/z
þ
(EI) 252 (M , 16%), 196 (31), 167 (5.4), 121 (37), 120 (21),
3
2
.1.9. 2-Chloro-5,5-dimethyl-3-phenylacetoxycyclohex-
-enone (16). Reaction of 4 (166 mg, 1.0 mmol) and
92 (13), 75 (6.0), 57 (100). Anal. calcd for C H ClO : C,
12 9 4
þ
57.05; H, 3.59. Found: C, 57.18; H, 3.69. HRMS (M ) calcd
for C H ClO 252.0189. Found, 252.0186.
phenylacetyl chloride (3.092 g, 20.0 mmol) under
Rh (OAc) (4.4 mg) afforded 16 (208 mg, 71%) as a liquid:
1
2
9
4
2
4
1
H NMR (300 MHz, CDCl ) d 7.35–7.27 (5H, m, ArH),
3
3.1.13. 3-Chloro-1-methyl-4-propanoyloxy-1H-quinolin-
2-one (20). Reaction of 6 (201 mg, 1.0 mmol) and propionyl
chloride (1.850 g, 20.0 mmol) under Rh (OAc) (4.4 mg)
3
.82 (2H, s, CH ), 2.51 (2H, s, CH ), 2.43 (2H, s, CH ), 1.09
2 2 2
1
3
(
(
6H, s, 2£CH ); C NMR (75 MHz, CDCl ) d 191.37
3
3
2
4
CvO, enone), 176.94 (CvO, ester), 167.25, 162.62,
afforded 20 (186 mg, 70%) as a solid; mp 134–1358C (from
1
1
3
32.21, 129.29, 128.61, 127.33, 51.08, 42.53, 40.87,
2.50, 27.85; IR (neat) 3065, 3032, 2963, 1769 (CvO,
hexane–ethylacetate); H NMR (300 MHz, CDCl ) d 7.64–
3
7.57 (2H, m, ArH), 7.41 (1H, d, J¼8.5 Hz, ArH), 7.28 (1H,
13
vinylic ester), 1694 (CvO, enone), 1634, 1497, 1454, 1412,
2
d, J¼8.0, 7.2 Hz ArH), 3.79 (3H, s, NCH ), 2.79 (2H, q,
3
1
1372, 1345, 1290, 1221, 1101, 1024, 947, 920 cm . Anal.
calcd for C H ClO : C, 65.64; H, 5.85. Found: C, 65.83;
H, 5.69.
J¼7.5 Hz, CH ), 1.36 (3H, t, J¼7.5 Hz, CH ); C NMR
2
3
(75 MHz, CDCl ) d 169.86 (CvO, ester), 158.77 (CvO,
3
1
6
17
3
amide), 151.48, 137.78, 131.56, 122.80, 118.35, 116.28,
114.47, 30.74, 27.33, 9.02; IR (KBr) 2988, 2946, 2922,
3
.1.10. 3-((E)-but-2-enoyloxy)-2-chloro-5,5-dimethyl-
1772 (CvO, vinylic ester), 1653 (CvO, amide), 1624,
1601, 1501, 1456, 1418, 1350, 1306, 1182, 1113, 1074,
1001, 972, 882 cm2 . Anal. calcd for C H ClNO : C,
cyclohex-2-enone (17). Reaction of 4 (166 mg, 1.0 mmol)
and crotonyl chloride (2.323 g, 20.0 mmol, 90%) under
Rh (OAc) (4.4 mg) afforded 17 (170 mg, 70%) as a solid;
1
1
3
12
3
58.77; H, 4.55. Found: C, 58.89; H, 4.32.
2
4
1
mp 59–608C (from hexane–ethylacetate); H NMR
(
(
(
300 MHz, CDCl ) d 7.21–7.12 (1H, m, vinylic CH), 5.95
3
3.1.14. 4-Butanoyloxy-3-chloro-1-methyl-1H-quinolin-2-
one (21). Reaction of 6 (201 mg, 1.0 mmol) and butyryl
chloride (2.131 g, 20.0 mmol) under Rh (OAc) (4.4 mg)
1H, d, J¼15.5 Hz, vinylic CH), 2.58 (2H, s, CH ), 2.46
2
2H, s, CH ), 1.95 (3H, d, J¼7.9 Hz, CH ), 1.11 (6H, s,
2
3
2
4

Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
9343
afforded 21(201 mg, 72%) as a solid; mp 928C (from
1
135.79, 133.13, 131.83, 128.00, 127.26, 127.03, 126.46,
125.00, 123.94, 35.80, 18.37, 13.72; IR (KBr) 2963, 2932,
2874, 1765 (CvO, vinylic ester), 1647 (CvO, enone),
1578, 1404, 1377, 1323, 1302, 1211, 1182, 1148, 1123,
1096, 1063, 965 cm2 . Anal. calcd for C H ClO : C,
hexane–ethylacetate); H NMR (300 MHz, CDCl ) d 7.64–
3
7
.56 (2H, m, ArH), 7.41 (1H, d, J¼8.5 Hz, ArH), 7.28 (1H,
d, J¼8.0, 7.2 Hz, ArH), 3.78 (3H, s, NCH ), 2.73 (2H, q,
3
1
J¼7.4 Hz, CH ), 1.92–1.84 (2H, m, CH ), 1.10 (3H, t,
2
2
17 13
3
1
3
J¼7.4 Hz, CH ); C NMR (75 MHz, CDCl ) d 168.99
67.89; H, 4.36. Found: C, 67.54; H, 4.47.
3
3
(
CvO, ester), 158.77 (CvO, amide), 151.52, 137.84,
1
1
31.55, 122.83, 118.43, 116.36, 114.48, 35.70, 30.75,
8.32, 13.65; IR (KBr) 2970, 2938, 2880, 1769 (CvO,
3.1.18. 4-Acetoxy-3-bromo-1-methyl-1H-quinolin-2-one
(25). Reaction of 6 (201 mg, 1.0 mmol) and acetyl bromide
(2.459 g, 20.0 mmol) under Rh (OAc) (4.4 mg) afforded
vinylic ester), 1655 (CvO, amide), 1624, 1601, 1456, 1418,
1
2
4
2
1
for C H ClNO : C, 60.11; H, 5.04. Found: C, 60.34; H,
360, 1304, 1182, 1243, 1105, 1078, 972 cm . Anal. calcd
25 (157 mg, 53%) as a solid; mp 1798C (from hexane–
1
ethylacetate); H NMR (300 MHz, CDCl ) d 7.66–7.58
3
1
4
14
3
5
.25.
(2H, m, ArH), 7.41 (1H, d, J¼8.5 Hz, ArH), 7.27 (1H, d,
J¼8.0, 7.2 Hz, ArH), 3.80 (3H, s, NCH ), 2.49 (3H, s, CH );
3
3
1
3
3
.1.15. 3-Acetoxy-2-chlorophenalen-1-one (22). Reaction
C NMR (75 MHz, CDCl ) d 166.29 (CvO, ester), 158.81
3
of 7 (220 mg, 1.0 mmol) and acetyl chloride (1.570 g,
0.0 mmol) under Rh (OAc) (4.4 mg) afforded 22
(CvO, amide), 153.71, 138.38, 131.76, 122.80, 116.35,
114.51, 110.68, 30.97, 20.60; IR (KBr) 2978, 1778 (CvO,
vinylic ester), 1649 (CvO, amide), 1620, 1564, 1454, 1420,
1360, 1319, 1304, 1190, 1161, 1100, 1067, 1007, 966,
889 cm2 . Anal. calcd for C H BrNO : C, 48.67; H, 3.40.
2
2
4
(
ethylacetate); H NMR (300 MHz, CDCl ) d 8.73 (1H, dd,
191 mg, 70%) as a solid; mp 195–1988C (from hexane–
1
3
1
J¼7.4, 1.2 Hz, ArH), 8.25 (1H, dd, J¼8.0, 1.1 Hz, ArH),
1
2
10
3
8
1
.10 (1H, dd, J¼8.2, 1.2 Hz, ArH), 7.89 (1H, dd, J¼7.4,
.1 Hz, ArH), 7.80 (1H, dd, J¼8.0, 7.4 Hz, ArH), 7.64 (1H,
Found: C, 48.96; H, 3.32.
1
3
dd, J¼8.2, 7.4 Hz, ArH), 2.52 (3H, s, CH ); C NMR
3.1.19. 3-Acetoxy-2-bromophenalen-1-one (26). Reaction
of 7 (220 mg, 1.0 mmol) and acetyl chloride (1.570 g,
20.0 mmol) under Rh (OAc) (4.4 mg) afforded 26
3
(
75 MHz, CDCl ) d 179.20 (CvO, enone), 167.05 (CvO,
3
ester), 154.93, 136.37, 133.69, 132.48, 132.37, 128.61,
27.86, 127.58, 126.99, 125.63, 125.48, 124.40, 21.04; IR
KBr) 2926, 1775 (CvO, vinylic ester), 1640 (CvO,
enone), 1574, 1404, 1368, 1323, 1225, 1215, 1182, 1157,
2
4
1
(
(146 mg, 46%) as a solid; mp 1828C (from hexane–
1
ethylacetate); H NMR (300 MHz, CDCl ) d 8.73 (1H, dd,
3
J¼7.4, 1.2 Hz, ArH), 8.24 (1H, d, J¼8.0 Hz, ArH), 8.12
(1H, d, J¼8.2 Hz, ArH), 7.88 (1H, d, J¼7.4 Hz, ArH), 7.80
(1H, dd, J¼8.0, 7.4 Hz, ArH), 7.63 (1H, dd, J¼8.2, 7.4 Hz,
2
1
þ
1
088, 1028, 1001, 960 cm ; m/z (EI) 272 (M , 10%), 230
(
(
100), 292 (15), 196 (15), 173 (22), 155 (30), 138 (34), 129
22), 105 (9), 87 (5), 71 (6), 57 (7). Anal. calcd for
1
3
ArH), 2.52 (3H, s, CH ); C NMR (75 MHz, CDCl ) d
3
3
C H ClO : C, 66.07; H, 3.33. Found: C, 65.95; H, 3.39.
3
178.91 (CvO, enone), 166.63 (CvO, ester), 156.85,
35.83, 133.36, 132.30, 132.04, 128.02, 127.49, 127.24,
1
5
9
1
3.1.16. 2-Chloro-3-propanoyloxyphenalen-1-one (23).
Reaction of 7 (220 mg, 1.0 mmol) and propionyl chloride
126.56, 125.57, 124.30, 118.81, 20.82; IR (KBr) 2930, 1779
(CvO, vinylic ester), 1645 (CvO, enone), 1580, 1404,
1374, 1323, 1227, 1181, 1146, 1088, 1026, 1005, 949,
876 cm2 . Anal. calcd for C H BrO : C, 56.81; H, 2.86.
(
1.850 g, 20.0 mmol) under Rh (OAc) (4.4 mg) afforded
2 4
1
2
ethylacetate); H NMR (300 MHz, CDCl ) d 8.69 (1H, d,
3 (212 mg, 74%) as a solid; mp 146–1478C (from hexane–
1
1
5
9
3
Found: C, 57.02; H, 2.63.
3
J¼7.5 Hz, ArH), 8.21 (1H, d, J¼8.0 Hz, ArH), 8.31 (1H, d,
J¼8.3 Hz, ArH), 7.84 (1H, d, J¼7.4 Hz, ArH), 7.76 (1H, dd,
J¼8.0, 7.6 Hz, ArH) 7.61 (1H, dd, J¼8.3, 7.4 Hz, ArH),
3.2. General procedure for the synthesis of a-benzyloxy
a-haloenones (32–46)
2
.83 (2H, q, J¼7.5 Hz, CH ), 1.38 (3H, t, J¼7.5 Hz, CH );
2
3
1
3
C NMR (75 MHz, CDCl ) d 178.71 (CvO, enone),
3
To a solution of diazodicarbonyl compound (1.0 mmol) and
benzyl halide (20 mmol) was added rhodium catalyst
(0.01 mmol) at room temperature under a N atmosphere.
1
70.14 (CvO, ester), 154.55, 135.84, 133.16, 131.88,
128.12, 127.33, 127.06, 126.49, 124.99, 124.02, 27.48, 9.12;
IR (KBr) 2963, 2932, 2874, 1765 (CvO, vinylic ester),
2
The reaction mixture was stirred at room temperature for
9–12 h or 508C for 6 h. The reaction mixture was purified
by flash column chromatography on silica gel to give the
product.
1
1
2
647 (CvO, enone), 1577, 1404, 1377, 1323, 1300, 1211,
2
1
182, 1148, 1122, 1063, 965, 842, 820, 777 cm ; m/z (EI)
þ
86 (M , 12%), 230 (100), 196 (22), 173 (14), 155 (14), 129
(
C, 67.03; H, 3.87. Found: C, 66.84; H, 3.69.
32), 112 (9), 71 (8), 57 (32). Anal. calcd for C H ClO :
16 11 3
3.2.1. 3-Benzyloxy-2-chlorophenalen-1-one (32). Reac-
tion of 7 (220 mg, 1.0 mmol) and benzyl chloride (2.52 g,
20.0 mmol) under Rh (OAc) (4.4 mg) afforded 32
3.1.17. 3-Butanoyloxy-2-chlorophenalen-1-one (24).
Reaction of 7 (220 mg, 1.0 mmol) and butyryl chloride
2
4
(263 mg, 82%) as a solid; mp 95–968C (from hexane–
1
(
2.131 g, 20.0 mmol) under Rh (OAc) (4.4 mg) afforded
2
ethylacetate); H NMR (300 MHz, CDCl ) d 8.69 (1H, d,
3
4
2
ethylacetate); H NMR (300 MHz, CDCl ) d 8.70 (1H, d,
4 (223 mg, 74%) as a solid; mp 1018C (from hexane–
1
J¼7.3 Hz, ArH), 8.20 (1H, d, J¼8.1 Hz, ArH), 8.06 (2H, dd,
J¼8.1, 7.3 Hz, ArH), 7.76 (1H, dd, J¼7.8, 7.6 Hz, ArH),
7.60–7.52 (3H, m, ArH), 7.44–7.34 (3H, m, ArH), 5.40
3
J¼7.4 Hz, ArH), 8.23 (1H, d, J¼8.0 Hz, ArH), 8.08 (1H, d,
J¼8.2 Hz, ArH), 7.85 (1H, d, J¼7.4 Hz, ArH), 7.78 (1H, dd,
J¼8.0, 7.4 Hz, ArH) 7.62 (1H, dd, J¼8.0, 7.4 Hz, ArH),
1
3
(2H, s, CH Ph); C NMR (75 MHz, CDCl ) d 179.60
2
3
(CvO, enone), 162.02, 135.80, 135.25, 132.67, 131.70,
131.15, 128.61, 128.39, 127.90, 126.92, 126.44, 125.48,
125.12, 121.94, 75.99; IR (KBr) 3030, 1647 (CvO, enone),
1561, 1453, 1406, 1372, 1310, 1221, 1204, 1144, 1094,
2
.77 (2H, q, J¼7.4 Hz, CH ), 1.95–1.87 (2H, m, CH ), 1.12
3 3
2
1
2
3
(
3H, t, J¼7.4 Hz, CH ); C NMR (75 MHz, CDCl ) d
1
78.64 (CvO, enone), 169.27 (CvO, ester), 154.52,

9344
Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
026, 965, 937, 903, 864, 839 cm2 ; m/z (EI) 320 (M ,
1
þ
enone), 1582, 1514, 1453, 1416, 1368, 1327, 1294, 1260,
1173, 1071, 1011, 897 cm2 . Anal. calcd for C H ClO :
C, 63.04; H, 5.67. Found: C, 62.72; H, 5.91.
1
9
1
1
%), 285 (20), 284 (10), 230 (8), 201 (7), 173 (11), 164 (11),
46 (30), 129 (15), 91 (100), 71 (7), 65 (11). Anal. calcd for
1
4
15
3
C H ClO : C, 74.89; H, 4.08. Found: C, 74.52; H, 4.39.
2
0
13
2
3.2.6. 3-Benzyloxy-2-chloro-5,5-dimethylcyclohex-2-
enone (37). Reaction of 4 (166 mg, 1.0 mmol) and benzyl
3
.2.2. 3-Benzyloxy-2-chlorocyclohex-2-enone (33). Reac-
tion of 1 (138 mg, 1.0 mmol) and benzyl chloride (2.520 g,
0.0 mmol) under Rh (OAc) (4.4 mg) afforded 33
chloride (2.520 g, 20.0 mmol) under Rh (OAc) (4.4 mg)
2
4
2
afforded 37 (207 mg, 78%) as a solid; mp 92–938C (from
1
2
4
(192 mg, 81%) as a solid; mp 98–998C (from hexane–
1
ethylacetate), H NMR (300 MHz, CDCl ) d 7.41–7.33
hexane–ethyl acetate); H NMR (300 MHz, CDCl ) d
3
7.40–7.32 (5H, m, ArH), 5.23 (2H, s, CH Ph), 2.51 (2H, s,
2
3
1
3
(
6
5H, m, ArH), 5.24 (2H, s, CH Ph), 2.67 (2H, dd, J¼6.2,
CH ), 2.34 (2H, s, CH ), 1.02 (6H, s, 2£CH ); C NMR
2
2
2
3
.1 Hz, CH ), 2.48 (2H, dd, J¼7.0, 6.2 Hz, CH ), 2.01–1.93
(75 MHz, CDCl ) d 191.02 (CvO), 168.62, 135.51, 128.79,
3
2
2
1
3
(
2H, m, CH ); C NMR (75 MHz, CDCl ) d 191.88
2
128.43, 126.57, 111.66, 70.43, 50.37, 46.06, 40.56, 32.05,
28.11; IR (KBr) 3038, 2963, 2934, 2880, 1649 (CvO,
enone), 1586, 1460, 1400, 1358, 1302, 1252, 1171, 1152,
1053, 1011, 943, 918, 900, 842 cm2 . Anal. calcd for
C H ClO : C, 68.05; H, 6.47. Found: C, 67.94; H, 6.72.
3
(
1
CvO), 171.14, 135.86, 129.33, 128.98, 127.41, 127.13,
12.99, 71.03 (CH Ph), 37.09 (CH ), 29.07 (CH ), 20.66
2
2
2
1
(
CH ); IR (KBr) 3036, 2945, 2889, 1657 (CvO, enone),
2
1
9
589, 1458, 1368, 1294, 1262, 1192, 1154, 1080, 1026, 1007,
1
1
5
17
2
22, 905, 817 cm2 ; m/z (EI) 236 (M , 10%), 146 (53), 120
þ
(31), 118 (92), 91 (100), 89 (16), 65 (59). Anal. calcd for
C H ClO : C, 65.97; H, 5.54. Found: C, 65.58, H, 5.20.
3.2.7. 2-Chloro-3-(3-methylbenzyloxy)-5,5-dimethyl-
cyclohex-2-enone (38). Reaction of 1 (138 mg, 1.0 mmol)
and 3-methylbenzyl chloride (2.812 g, 20.0 mmol) under
Rh (OAc) (4.4 mg) afforded 38 (184 mg, 66%) as a solid;
1
3
13
2
3
.2.3. 2-Chloro-3-(3-methylbenzyloxy)cyclohex-2-enone
34). Reaction of 1 (138 mg, 1.0 mmol) and 3-methylbenzyl
chloride (2.812 g, 20.0 mmol) under Rh (OAc) (4.4 mg)
2
4
1
(
mp 115–1168C (from hexane–ethylacetate), H NMR
(300 MHz, CDCl ) d 7.25 (1H, dd, J¼8.0, 7.5 Hz, ArH),
13
2
4
3
afforded 34 (173 mg, 69%) as a solid; mp 117–1188C (from
1
7.14–7.11 (3H, m, ArH), 5.19 (2H, s, CH Ph), 2.51 (2H, s,
2
hexane–ethylacetate), H NMR (300 MHz, CDCl ) d 7.28–
3
CH ), 2.34 (5H, s, CH and CH ), 1.02 (3H, s, CH );
C
NMR (75 MHz, CDCl ) d 191.39 (CvO), 169.11, 138.52,
2
2
3
3
7
ArH), 7.1–7.13 (3H, m, ArH), 5.20 (2H, s, CH Ph), 2.67
.23 (1H, dd, J¼8.0, 7.5 Hz, ArH), 7.15–7.12 (3H, m,
3
135.34, 129.16, 128.65, 127.22, 123.61, 111.44, 70.53,
50.24, 40.48, 32.05, 28.03, 21.30; IR (KBr) 3029, 2961,
2872, 1667 (CvO, enone), 1595, 1468, 1358, 1298, 1242,
1173, 1053, 1015, 947, 926 cm2 . Anal. calcd for
C H ClO : C, 68.93; H, 6.87. Found: C, 68.65, H, 6.61.
2
(
2
2H, t, J¼6.2 Hz, CH ), 2.48 (2H, dd, J¼7.0, 6.3 Hz, CH ),
2
2
1
3
.34 (3H, s, CH ), 2.03–1.94 (2H, m, CH ); C NMR
3 2
1
(
75 MHz, CDCl ) d 191.34 (CvO), 170.77, 138.58, 135.32,
3
1
2
1
29.22, 128.70, 127.34, 123.74, 112.35, 70.63, 36.59, 26.96,
1.35, 20.16; IR (KBr) 2949, 1647 (CvO, enone), 1584,
458, 1421, 1373, 1350, 1300, 1265, 1198, 1078, 1017, 920,
1
6
19
2
3.2.8. 2-Chloro-3-(4-methoxybenzyloxy)-5,5-dimethyl-
cyclohex-2-enone (39). Reaction of 4 (166 mg, 1.0 mmol)
and 4-methoxybenzyl chloride (3.140 g, 20.0 mmol) under
Rh (OAc) (4.4 mg) afforded 39 (280 mg, 95%) as a solid;
2
1
8
Found: C, 67.35, H, 6.20.
91 cm . Anal. calcd for C H ClO : C, 67.07; H, 6.03.
14 15 2
2
4
1
3
(
.2.4. 2-Chloro-3-(4-methylbenzyloxy)cyclohex-2-enone
35). Reaction of 1 (138 mg, 1.0 mmol) and 4-methylbenzyl
chloride (2.812 g, 20.0 mmol) under Rh (OAc) (4.4 mg)
mp 142–1438C (from hexane–ethyl acetate); H NMR
(300 MHz, CDCl ) d 7.27 (2H, d, J¼8.6 Hz, ArH), 6.89
3
(2H, d, J¼8.6 Hz, ArH), 5.16 (2H, s, CH Ph), 3.79 (3H, s,
2
4
2
afforded 35 (203 mg, 81%) as a solid; mp 92–938C (from
1
OCH ), 2.52 (2H, s, CH ), 2.35 (2H, s, CH ), 1.03 (6H, s,
3
2
2
13
hexane–ethylacetate), H NMR (300 MHz, CDCl ) d 7.23
3
2£CH ); C NMR (75 MHz, CDCl ) d 191.02 (CvO),
3
3
(
(
2H, d, J¼7.5 Hz, ArH), 7.17 (2H, d, J¼7.5 Hz, ArH), 5.19
168.79, 159.69, 128.49, 127.45, 114.14, 111.59, 70.44,
55.25, 50.38, 40.72, 32.07, 28.17; IR (KBr) 2957, 1649,
(CvO, enone), 1586, 1514, 1462, 1304, 1246, 1175, 1032,
2H, s, CH Ph), 2.67 (2H, t, J¼6.1 Hz, CH ), 2.47 (2H, dd,
2
2
J¼7.0, 6.3 Hz, CH ), 2.34 (3H, s, CH ), 1.99–1.93 (2H, m,
2
3
1
3
21
CH ); C NMR (75 MHz, CDCl ) d 191.51 (CvO),
2
945 cm . Anal. calcd for C H ClO : C, 65.19; H, 6.50.
16 19
3
3
1
5
71.12, 159.66, 128.54, 127.23, 114.10, 112.15, 70.51,
5.19, 36.51, 26.99, 20.09; IR (KBr) 2949, 1657 (CvO,
Found: C, 65.36; H, 6.82.
enone), 1591, 1516, 1454, 1420, 1368, 1329, 1294, 1273,
1
for C H ClO : C, 67.07; H, 6.03. Found: C, 66.95, H, 6.12.
3.2.9. 4-Benzyloxy-3-chlorochromen-2-one (40). Reaction
of 5 (188 mg, 1.0 mmol) and benzyl chloride (2.520 g,
20.0 mmol) under Rh (OPiv) (6.1 mg) afforded 40
190, 1150, 1082, 1038, 1007, 926, 820 cm2 . Anal. calcd
1
1
4
15
2
2
4
(
158 mg, 55%) as a solid; mp 688C (from hexane–ethyl
1
3
.2.5. 2-Chloro-3-(4-methoxybenzyloxy)cyclohex-2-
enone (36). Reaction of 1 (138 mg, 1.0 mmol) and
-methoxybenzyl chloride (3.040 g, 20.0 mmol) under
Rh (OAc) (4.4 mg) afforded 36 (248 mg, 93%) as a solid;
acetate); H NMR (300 MHz, CDCl ) d 7.71–7.24 (9H, m,
3
ArH), 5.54 (2H, s, CH Ph); C NMR (75 MHz, CDCl ) d
2
1
3
3
4
161.51 (CvO, ester), 159.42, 151.08, 135.08, 132.38,
128.97, 128.74, 128.54, 128.33, 124.56, 123.53, 117.39,
116.50, 107.07, 75.81; IR (KBr) 3067, 3036, 1732 (CvO,
ester), 1609, 1557, 1487, 1454, 1389, 1333, 1275, 1206,
1161, 1098, 1036, 1003, 914, 860 cm2 . Anal. calcd for
C H ClO : C, 67.03; H, 3.87. Found: C, 66.70; H, 3.92.
2
4
1
mp 139–1408C (from hexane–ethyl acetate); H NMR
(
(
300 MHz, CDCl ) d 7.27 (2H, d, J¼8.6 Hz, ArH), 6.91
3
1
2H, d, J¼8.6 Hz, ArH), 5.16 (2H, s, CH Ph), 3.80 (3H, s,
2
OCH ), 2.68 (2H, m, CH ), 2.47 (2H, m, CH ), 2.00 (2H, m,
3
CH2); C NMR (75 MHz, CDCl ) d 191.37 (CvO),
3
2
2
16 11
3
1
3
1
5
70.92, 159.67, 128.56, 127.26, 114.12, 112.23, 70.50,
5.21, 36.56, 27.02, 20.14; IR (KBr) 2957, 1649 (CvO,
3.2.10. 3-Benzyloxy-2-bromo-cyclohex-2-enone (41).
Reaction of 1 (138 mg, 1.0 mmol) and benzyl bromide

Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
9345
(
3.420 g, 20.0 mmol) under Rh (OAc) (4.4 mg) afforded
2
J¼8.0, 1.6 Hz, ArH), 7.59–7.23 (8H, m, ArH), 5.45 (2H, s,
CH Ph); C NMR (75 MHz, CDCl ) d 164.40 (CvO,
2 3
4
1
3
4
ethyl acetate); H NMR (300 MHz, CDCl ) d 7.38–7.33
(
6
CH ); C NMR (75 MHz, CDCl ) d 191.45 (CvO),
1
3
1 (188 mg, 67%) as a solid; mp 104–1058C (from hexane–
1
ester), 159.29, 151.93, 135.02, 132.63, 129.02, 128.76,
128.46, 124.58, 123.47, 117.57, 116.66, 99.06, 76.00; IR
(KBr) 3079, 2890, 1725 (CvO, ester), 1605, 1553, 1451,
1321, 1273, 1215, 1190, 1152, 1094, 1032, 984, 943,
912 cm2 . Anal. calcd for C H BrO : C, 58.03; H, 3.35.
3
5H, m, ArH), 5.25 (2H, s, CH Ph), 2.66 (2H, dd, J¼6.3,
2
.1, CH ), 2.51 (2H, dd, J¼6.8, 6.3, CH ), 1.99 (2H, m,
2
2
1
2 3
3
1
72.75, 135.23, 128.72, 128.32, 126.81, 126.50, 70.48,
6.50, 27.27, 20.32; IR (KBr) 3063, 3036, 2949, 2887, 1655
1
6
11
3
Found: C, 58.27; H, 3.13.
(
CvO, enone), 1585, 1499, 1458, 1368, 1287, 1260, 1192,
2
1
1154, 1080, 1026, 987, 920, 904 cm . Anal. calcd for
C H BrO : C, 55.54; H, 4.66. Found: C, 55.48; H, 4.85.
3.2.15. 3-Benzyloxy-2-bromophenalen-1-one (46). Reac-
tion of 7 (220 mg, 1.0 mmol) and benzyl bromide (3.420 g,
1
3
13
2
20.0 mmol) under Rh (OAc) (4.4 mg) afforded 46
(310 mg, 85%) as a solid; mp 1168C (from hexane–
ethylacetate); H NMR (300 MHz, CDCl ) d 8.71 (1H, dd,
3
2 4
3
.2.11. 2-Bromo-3-(2-methylbenzyloxy)cyclohex-2-
enone (42). Reaction of 1 (138 mg, 1.0 mmol) and
-methylbenzyl bromide (3.70 g, 20.0 mmol) under
Rh (OAc) (4.4 mg) afforded 42 (162 mg, 55%) as a solid;
1
2
J¼7.4, 1.1 Hz, ArH), 8.22 (1H, dd, J¼8.1, 1.1 Hz, ArH),
8.07 (2H, dd, J¼8.1, 7.3 Hz, ArH), 7.78 (1H, dd, J¼7.8,
7.6 Hz, ArH), 7.60–7.55 (3H, m, ArH), 7.46–7.36 (3H, m,
2
4
1
mp 170–1718C (from hexane–ethyl acetate); H NMR
(
1
3
300 MHz, CDCl ) d 7.33 (1H, d, J¼7.1 Hz, ArH), 7.28–
ArH), 5.34 (2H, s, CH Ph); C NMR (75 MHz, CDCl ) d
2 3
3
7
.19 (3H, m, ArH), 5.22 (2H, s, CH Ph), 2.71 (2H, t,
2
179.88 (CvO, enone), 164.36, 135.79, 135.34, 132.91,
131.94, 131.63, 128.71, 128.68, 128.47, 127.98, 127.94,
127.13, 126.54, 125.77, 115.98, 76.21; IR (KBr) 3032,
2953, 2890, 1644 (CvO, enone), 1574, 1557, 1406, 1383,
J¼6.2 Hz, CH ), 2.52 (2H, dd, J¼6.7, 6.2 Hz, CH ), 2.37
2
2
1
3
(
CDCl ) d 191.28 (CvO), 172.49, 136.30, 133.23, 130.63,
3H, s, CH ), 2.06–1.98 (2H, m, CH ); C NMR (75 MHz,
3 2
3
2
1
1
1
1
28.77, 127.77, 126.23, 103.72, 69.36, 36.65, 27.38, 20.53,
8.99; IR (KBr) 2953, 1658 (CvO, enone), 1586, 1487,
1308, 1223, 1202, 1157, 1094, 1026, 957, 909 cm . Anal.
calcd for C H BrO : C, 65.77; H, 3.59. Found: C, 65.85;
H, 3.81.
2
0
13
2
454, 1418, 1370, 1258, 1192, 1152, 1080, 1036, 916 cm21
.
Anal. calcd for C H BrO : C, 56.97; H, 5.12. Found: C,
2
1
4
15
5
6.69; H, 5.31.
3.3. General procedure for the synthesis of b-halo-
methoxy a-haloenones (49–56)
3
.2.12. 2-Bromo-3-(4-methylbenzyloxy)cyclohex-2-
enone (43). Reaction of 1 (138 mg, 1.0 mmol) and
-methylbenzyl bromide (3.70 g, 20.0 mmol) under
Rh (OAc) (4.4 mg) afforded 43 (192 mg, 65%) as a solid;
To a solution of diazodicarbonyl compound (1.0 mmol) and
methylene halide (2 mL) was added rhodium catalyst
(0.005 mmol) at room temperature under a N atmosphere.
The reaction mixture was stirred at room temperature for
4–7 h or 508C for 5 h. The halide was evaporated under
reduced pressure to give the residue. The residue was
purified by flash column chromatography on silica gel to
give the product.
4
2
4
2
1
mp 958C (from hexane–ethyl acetate); H NMR (300 MHz,
CDCl ) d 7.23 (2H, d, J¼8.2 Hz, ArH), 7.18 (2H, d,
3
J¼8.2 Hz, ArH), 5.20 (2H, s, CH Ph), 2.651 (2H, t,
2
J¼6.2 Hz, CH ), 2.49 (2H, dd, J¼6.7, 6.2 Hz, CH ), 2.34
2
2
1
3
(3H, s, CH ), 2.02–1.93 (2H, m, CH ); C NMR (75 MHz,
3 2
CDCl ) d 191.40 (CvO), 172.78, 138.33, 132.29, 129.46,
3
1
3
1
26.72, 103.78, 70.62, 36.61, 27.40, 21.13, 20.43; IR (KBr)
027, 2951, 2920, 2876, 1657 (CvO, enone), 1584, 1516,
3.3.1. 2-Chloro-3-chloromethoxyphenalen-1-one (49).
Reaction of 7 (220 mg, 1.0 mmol) and methylene chloride
(2 mL) under Rh (OAc) (2.2 mg) afforded 49 (226 mg,
366, 1289, 1273, 1229, 1188, 1148, 1080, 1036, 986 cm21
.
2
4
1
Anal. calcd for C H BrO : C, 56.97; H, 5.12. Found: C,
1
81%) as a solid; mp 1418C (from hexane–ethylacetate); H
NMR (300 MHz, CDCl ) d 8.72 (1H, dd, J¼7.5, 1.1 Hz,
4
15
2
5
6.85; H, 5.27.
3
ArH), 8.32–8.24 (2H, m, ArH), 8.11 (1H, dd, J¼8.0,
1.1 Hz, ArH), 7.79 (1H, dd, J¼8.0, 7.5 Hz, ArH), 7.69 (1H,
3.2.13. 3-Benzyloxy-2-bromo-5,5-dimethyl-cyclohex-2-
enone (44). Reaction of 6 (166 mg, 1.0 mmol) and benzyl
bromide (3.420 g, 20.0 mmol) under Rh (OAc) (4.4 mg)
2
1
3
dd, J¼8.0, 7.5 Hz, ArH), 6.19 (2H, s, CH ); C NMR
2
(75 MHz, CDCl ) d 179.03 (CvO, enone), 159.60, 135.79,
3
4
afforded 44 (216 mg, 70%) as a solid; mp 102–1038C (from
1
133.22, 131.60, 129.42, 127.74, 127.08, 126.54, 125.11,
124.79, 122.62, 80.11; IR (KBr) 3065, 2926, 1657 (CvO,
enone), 1626, 1578, 1562, 1454, 1404, 1377, 1343, 1314,
hexane–ethyl acetate); H NMR (300 MHz, CDCl ) d
3
7
.38–7.35 (5H, m, ArH), 5.24 (2H, s, CH Ph), 2.50 (2H, s,
2
1
3
21
CH ), 2.38 (2H, s, CH ), 1.02 (6H, s, 2£CH ); C NMR
1206, 1146, 1098, 1030, 1003, 986, 934, 839 cm . Anal.
2
2
3
(
75 MHz, CDCl ) d 191.05 (CvO), 170.50, 135.54, 128.84,
3
calcd for C H Cl O : C, 60.24; H, 2.89. Found: C, 60.03;
14
8
2 2
þ
H, 2.81. HRMS calcd for C H Cl O (M ) 277.9901.
14 8 2 2
1
IR (KBr) 3063, 2957, 2872, 1667 (CvO, enone), 1589,
28.45, 126.53, 103.11, 70.47, 50.45, 41.06, 32.32, 28.11;
Found 277.9900.
1
calcd for C H BrO : C, 58.27; H, 5.54. Found: C, 58.57;
H, 5.91.
462, 1352, 1292, 1244, 1171, 1038, 1001, 910 cm2 . Anal.
1
3.3.2. 2-Chloro-3-chloromethoxycyclohex-2-enone (50).
Reaction of 1 (138 mg, 1.0 mmol) and methylene chloride
1
5
17
2
(
2 mL) under Rh (OAc) (2.2 mg) afforded 50 (154 mg,
2 4
1
3
.2.14. 4-Benzyloxy-3-bromochromen-2-one (45). Reac-
tion of 5 (188 mg, 1.0 mmol) and benzyl bromide (3.420 g,
0.0 mmol) under Rh (OPiv)4 (4.4 mg) afforded 45
79%) as a solid; mp 758C (from hexane–ethyl acetate); H
NMR (300 MHz, CDCl ) d 5.82 (2H, s, CH ), 2.83 (2H, t,
3
2
2
J¼6.2 Hz, CH ), 2.55 (2H, dd, J¼7.0, 6.3 Hz, CH ), 2.14–
2.05 (2H, m, CH ); C NMR (75 MHz, CDCl ) d 191.78
2 3
(CvO), 167.79, 116.03, 74.93, 37.20, 26.18, 20.49; IR
2
2
2
1
3
(
acetate); H NMR (300 MHz, CDCl ) d 7.67 (1H, dd,
199 mg, 60%) as a solid; mp 1208C (from hexane–ethyl
1
3

9346
Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
(
1
KBr) 3319, 3067, 3002, 2961, 1672 (CvO, enone), 1603,
426, 1372, 1281, 1211, 1184, 1078, 1047, 1017, 992,
26 cm . Anal. calcd for C H Cl O : C, 43.11; H, 4.13.
7 8 2 2
IR (KBr) 2961, 1670 (CvO), 1603, 1466, 1363, 1304, 1246,
1198, 1159, 1069, 1006, 922 cm2 . Anal. calcd for
C H Br O : C, 34.65; H, 3.88. Found: C, 34.49; H, 3.74.
1
2
1
9
Found: C, 43.42; H, 4.31.
9
12
2 2
þ
HRMS calcd for C H Br O (M ) 309.9204. Found,
9 12 2 2
309.9201.
3.3.3. 2-Chloro-3-chloromethoxy-5-phenylcyclohex-2-
enone (51). Reaction of 2 (214 mg, 1.0 mmol) and
3.3.8. 2-Chloro-3-chloromethoxyphenalen-1-one (56).
Reaction of 7 (220 mg, 1.0 mmol) and methylene bromide
(2 mL) under Rh (OAc) (2.2 mg) afforded 56 (313 mg,
methylene chloride (2 mL) under Rh (OAc) (2.2 mg)
4
2
afforded 51 (244 mg, 90%) as a solid; mp 92–938C (from
1
2
4
1
hexane–ethylacetate); H NMR (300 MHz, CDCl ) d 7.40–
3
85%) as a solid; mp 1518C (from hexane–ethylacetate); H
NMR (300 MHz, CDCl ) d 8.73 (1H, d, J¼7.4 Hz, ArH),
7
3
1
1
3
1
.26 (5H, m, ArH), 5.82 (2H, m, CH ), 3.44 (1H, m, CH),
2
3
1
3
.17–2.72 (4H, m, 2£CH ); C NMR (75 MHz, CDCl ) d
8.31 (1H, d, J¼7.4 Hz, ArH), 8.26 (1H, d, J¼8.0 Hz, ArH),
8.14 (1H, d, J¼8.0 Hz, ArH), 7.79 (1H, dd, J¼8.0, 7.4 Hz,
2
3
90.23 (CvO, enone), 165.03, 141.05, 129.00, 127.61,
26.55, 115.72, 74.43, 43.48, 38.41, 33.52; IR (KBr) 3065,
000, 2951, 1682 (CvO), 1615, 1456, 1381, 1348, 1287,
ArH), 7.69 (1H, dd, J¼8.0, 7.4 Hz, ArH), 6.36 (2H, s, CH );
2
1
3
C NMR (75 MHz, CDCl ) d 179.22 (CvO, enone),
3
2
1
254, 1184, 1071, 1040, 974, 939 cm . Anal. calcd for
162.09, 135.82, 133.46, 132.01, 131.71, 129.71, 127.57,
127.22, 126.52, 125.35, 125.09, 115.80, 70.53; IR (KBr)
C H Cl O : C, 57.59; H, 4.46. Found: C, 57.83; H, 4.69.
2 2
1
3
12
3
067, 1649 (CvO, enone), 1626, 1576, 1559, 1447, 1404,
2
1
3
2
.3.4. 2-Chloro-3-chloromethoxy-5,5-dimethylcyclohex-
-enone (52). Reaction of 4 (166 mg, 1.0 mmol) and
1319, 1289, 1202, 1144, 1094, 1030, 993, 914 cm . Anal.
calcd for C H Br O : C, 45.69; H, 2.19. Found: C, 45.33;
þ
H, 2.36. HRMS calcd for C H Br O (M ) 365.8891.
14 8 2 2
1
4
8
2 2
methylene chloride (2 mL) under Rh (OAc) (2.2 mg)
2
4
afforded 52 (181 mg, 81%) as a solid; mp 49–508C (from
1
Found, 365.8893.
hexane–ethylacetate); H NMR (300 MHz, CDCl ) d 5.81
3
(
2H, s, CH ), 2.67 (2H, s, CH ), 2.42 (2H, s, CH ), 1.13 (6H,
2
3.4. General procedure for the synthesis of b-hydroxy
a-haloenones (58–65)
2
2
1
3
s, 2£CH ); C NMR (75 MHz, CDCl ) d 191.12 (CvO,
3
3
enone), 165.32, 114.76, 74.32, 50.32, 39.19, 32.25, 28.01;
IR (KBr) 2963, 1678 (CvO), 1612, 1468, 1364, 1292, 1260,
To a solution of diazodicarbonyl compound (1.0 mmol) and
alkyl halide (2 mL) was added rhodium catalyst
(0.005 mmol) at room temperature under a N atmosphere.
2
1
1206, 1167, 1074, 1017, 951 cm . Anal. calcd for
C H Cl O : C, 48.45; H, 5.42. Found: C, 48.35; H, 5.19.
9
12
2
2
2
The reaction mixture was stirred at room temperature for
10 h. The halide was evaporated under reduced pressure to
give the residue. The residue was purified by flash column
chromatography on silica gel to give the product.
3
.3.5. 2-Chloro-3-chloromethoxy-d -5,5-dimethylcyclo-
2
hex-2-enone (53). Reaction of 4 (166 mg, 1.0 mmol) and
CD Cl (2 mL) under Rh (OAc) (2.2 mg) afforded 53
2
2
2
4
(
ethylacetate); H NMR (300 MHz, CDCl ) d 2.66 (2H, s,
169 mg, 75%) as a solid; mp 538C (from hexane–
1
8
3.4.1. 2-Chloro-3-hydroxycyclohex-2-enone (58). Reac-
tion of 1 (138 mg, 1.0 mmol) and n-butyl chloride (2 mL)
under Rh (OAc) (2.2 mg) afforded 58 (140 mg, 96%) as a
3
1
3
CH ), 2.41 (2H, s, CH ), 1.13 (6H, s, 2£CH ); C NMR
2
2
3
(
75 MHz, CDCl ) d 191.02 (CvO, enone), 165.42, 115.73,
3
2
4
1
7
1
9
2
7.20, 50.60, 39.60, 31.88, 28.13; IR (KBr) 2963, 2874,
676 (CvO), 1613, 1470, 1296, 1236, 1103, 1055,
solid; mp 197–1988C (from hexane–ethyl acetate); H
NMR (300 MHz, CDCl ) d 6.52 (1H, s, OH), 2.64 (2H, t,
3
2
1
þ
95 cm
24.0338. Found, 224.0336.
.
HRMS calcd for C H D Cl O (M )
2
J¼6.2 Hz, CH ), 2.53 (2H, t, J¼6.6 Hz, CH ), 2.06–1.95
9
10
2
2
2
2
(2H, m, CH ); IR (KBr) 3043 (br OH), 1655 (CvO, enone),
2
1
1
579, 1424, 1325, 1198, 1144, 1015, 972 cm2
.
3.3.6. 2-Bromo-3-bromomethoxy-5-phenylcyclohex-2-
enone (54). Reaction of 2 (214 mg, 1.0 mmol) and
8
3.4.2. 2-Bromo-3-hydroxycyclohex-2-enone (59). Reac-
tion of 1 (138 mg, 1.0 mmol) and ethyl bromide (2 mL)
under Rh (OAc) (2.2 mg) afforded 59 (181 mg, 95%) as a
methylene bromide (2 mL) under Rh (OAc) (2.2 mg)
4
2
afforded 54 (270 mg, 75%) as a solid; mp 128–1298C
1
2
4
1
(
from hexane–ethylacetate); H NMR (300 MHz, CDCl ) d
3
solid; mp 177–1788C (from hexane–ethyl acetate); H
NMR (300 MHz, CDCl ) d 6.51 (1H, s, OH), 2.65 (2H, t,
7
.40–7.22 (5H, m, ArH), 5.94 (2H, m, CH ), 3.44 (1H, m,
2
3
1
3
CH), 3.17–3.12 (1H, m), 2.96–2.74 (3H, m); C NMR
75 MHz, CDCl ) d 190.95 (CvO, enone), 168.58, 141.88,
J¼6.2 Hz, CH ), 2.55 (2H, t, J¼6.6 Hz, CH ), 2.05–1.96
2
2
(
(2H, m, CH ); IR (KBr) 3111 (br OH), 1655 (CvO, enone),
2
3
1591, 1422, 1318, 1194, 1144, 1067, 993, 967 cm2
.
1
1
29.00, 127.50, 126.60, 107.66, 63.67, 43.43, 38.66, 33.81;
IR (KBr) 3067, 1678 (CvO), 1609, 1456, 1339, 1279, 1242,
2
1
1175, 1069, 959, 959 cm . Anal. calcd for C H Br O :
1
C, 43.37; H, 3.36. Found: C, 43.66; H, 3.61.
3.4.3. 2-Iodo-3-hydroxycyclohex-2-enone (60). Reaction
of 1 (138 mg, 1.0 mmol) and propyl iodide (2 mL) under
Rh (OAc) (2.2 mg) afforded 60 (228 mg, 96%) as a solid;
mp137–1388C (from hexane–ethyl acetate); H NMR
(300 MHz, CDCl ) d 6.33 (1H, s, OH), 2.69 (2H, t,
3
12
2 2
2
4
1
3
2
.3.7. 2-Bromo-3-bromomethoxy-5,5-dimethylcyclohex-
-enone (55). Reaction of 4 (166 mg, 1.0 mmol) and
3
methylene bromide (2 mL) under Rh (OAc) (2.2 mg)
2
J¼6.2 Hz, CH ), 2.57 (2H, t, J¼6.6 Hz, CH ), 2.03–1.91
4
2
2
afforded 55 (243 mg, 78%) as a solid; mp 57–588C (from
1
(2H, m, CH ); IR (KBr) 3099 (br OH), 1645 (CvO, enone),
2
21
hexane–ethylacetate); H NMR (300 MHz, CDCl ) d 5.94
3
1576, 1418, 1370, 1314, 1190, 1144, 1065, 981, 955 cm
;
1
3
(
2H, s, CH ), 2.68 (2H, s, CH ), 2.45 (2H, s, CH ), 1.15 (6H,
2
C NMR (75 MHz, CDCl þDMSO-d ) d 78.26, 32.85,
20.29. Anal. calcd for C H IO : C, 30.28; H, 2.96. Found:
6 7 2
2
2
3
6
1
3
s, 2£CH ); C NMR (75 MHz, CDCl ) d 190.98 (CvO,
3
3
enone), 167.11, 106.95, 63.74, 50.54, 39.55, 32.51, 28.06;
C, 30.54; H, 3.05.

Y. R. Lee et al. / Tetrahedron 59 (2003) 9333–9347
9347
3
.4.4. 2-Chloro-3-hydroxy-5-phenylcyclohex-2-enone
Acknowledgements
(
(
61). Reaction of 2 (214 mg, 1.0 mmol) and n-butyl chloride
2 mL) under Rh (OAc) (2.2 mg) afforded 61 (205 mg,
2%) as a solid; mp 2708C (from hexane–ethyl acetate); H
This work was supported by the Korea Research Foundation
Grant (KRF-2001-041-D00145). Dr Ronald Tepper in
discussion of this work is greatly appreciated.
2
4
1
9
NMR (300 MHz, CDCl ) d 7.37–7.22 (5H, m, ArH), 6.52
3
(
1H, s, OH), 3.44–3.37 (1H, m, CH), 2.89–2.66 (4H, m,
1
3
2
1
3
1
£CH ); C NMR (75 MHz, CDCl þDMSO-d ) ( 141.61,
2
3
6
28.43, 126.78, 126.26, 107.97, 37.91, 34.13; IR (KBr)
099 (br OH), 1645 (CvO, enone), 1576, 1418, 1370, 1314,
References
2
1
190, 1144, 1065, 981, 955 cm . Anal. calcd for
1
2
. Larock, L. C. Comprehensive Organic Transformations; 2nd
ed. VCH: New York, 1999; pp 715.
. (a) Johnson, C. R.; Braun, M. P. J. Am. Chem. Soc. 1993, 115,
C H ClO : C, 64.73; H, 4.98. Found: C, 64.99; H, 4.65.
1
2
11
2
3
(
(
.4.5. 2-Bromo-3-hydroxy-5-phenylcyclohex-2-enone
62). Reaction of 2 (214 mg, 1.0 mmol) and ethyl bromide
2 mL) under Rh (OAc) (2.2 mg) afforded 62 (240 mg,
1
1014. (b) Johnson, C. R.; Harikrishnan, L. S.; Golebiowski, A.
Tetrahedron Lett. 1994, 35, 7735. (c) Johnson, C. R.; Adams,
J. P.; Collins, M. A. J. Chem. Soc., Perkin Trans. 1 1993, 1.
. (a) Kowalski, C.; Weber, A. E.; Fields, K. W. J. Org. Chem.
1982, 47, 5088. (b) Benhida, R.; Blanchard, P.; Fourrey, J.-L.
Tetrahedron Lett. 1998, 39, 6849.
2
4
1
90%) as a solid; mp 2058C (from hexane–ethyl acetate); H
NMR (300 MHz, CDCl ) d 7.37–7.22 (5H, m, ArH), 6.57
3
3
(
1H, s, OH), 3.48–3.37 (1H, m, CH), 2.89–2.69 (4H, m,
1
3
2
1
£CH ); C NMR (75 MHz, CDCl þDMSO-d ) d 141.61,
2
3
6
4. Dieter, R. K.; Nice, L. E.; Velu, S. E. Tetrahedron Lett. 1996,
7, 2377.
. Righi, G.; Bovicelli, P.; Sperandio, A. Tetrahedron Lett. 1999,
0, 5889.
6. Ley, S.; Whittle, A. J. Tetrahedron Lett. 1981, 22, 3301.
28.35, 126.70, 126.21, 99.12, 40.49, 38.11; IR (KBr) 3099
3
(
br OH), 1645 (CvO, enone), 1576, 1418, 1370, 1314,
5
190, 1144, 1065, 981, 955 cm2 . Anal. calcd for
1
1
C H BrO : C, 53.96; H, 4.15. Found: C, 53.84; H, 4.39.
4
1
2
11
2
7
8
9
. Dauben, W.; Warshawsky, A. M. Synth. Commun. 1988, 18,
323.
3
.4.6. 2-Chloro-3-hydroxy-5,5-dimethylcyclohex-2-
1
1
7
enone (63). Reaction of 4 (166 mg, 1.0 mmol) and
ethylene dichloride (2 mL) under Rh (OAc) (2.2 mg)
afforded 63 (171 mg, 98%) as a solid; mp 162–1638C
. Shepherd, R. G.; White, A. C. J. Chem. Soc., Perkin Trans. 1
1987, 2153.
2
4
. (a) Bovonsombat, P.; Angara, G. J.; Mc Nelis, E. Tetrahedron
Lett. 1994, 35, 6787. (b) Johnson, C. R.; Adams, J. P.; Braun,
M. P.; Senanayake, C. B. W.; Wovkulich, P. M.; Uskokovic,
M. R. Tetrahedron Lett. 1992, 33, 917. (c) Sha, C.-K.; Huang,
S.-J. Tetrahedron Lett. 1995, 36, 6927. (d) Whang, J. P.; Yang,
S. G.; Kim, Y. H. Chem. Commun. 1997, 1335. (e) Matsuo, K.;
Ishida, S.; Takuno, Y. Chem. Pharm. Bull. 1994, 42, 1149.
0. (a) Doyle, M. P.; Mckervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds: from
Cyclopropanes to Ylides; Wiley: New York, 1997. (b) Padwa,
A.; Weingarten, M. D. Chem. Rev. 1996, 96, 223. (c) Ye, T.;
Mckervey, M. A. Chem. Rev. 1994, 94, 1091. (d) Padwa, A.
Acc. Chem. Res. 1991, 24, 22. (e) Doyle, M. P. Acc. Chem.
Rev. 1986, 19, 348.
1
(
from hexane–ethyl acetate); H NMR (300 MHz, CDCl ) d
3
6
.48 (1H, s, OH), 2.50 (2H, s, CH ), 2.39 (2H, s, CH ), 1.10
2 2
(
(
1
6H, s, 2£CH ); IR (KBr) 3000 (br OH), 2963, 2874, 1647
013, 943 cm2
3
CvO, enone), 1616, 1582, 1341, 1292, 1262, 1148, 1127,
.
1
3
.4.7. 2-Bromo-3-hydroxy-5,5-dimethylcyclohex-2-
1
enone (64). Reaction of 4 (166 mg, 1.0 mmol) and ethylene
dibromide (2 mL) under Rh (OAc) (2.2 mg) afforded 64
(210 mg, 96%) as a solid; mp 175–1768C (from hexane–
1
ethyl acetate); H NMR (300 MHz, CDCl ) d 6.46 (1H, s,
OH), 2.50 (2H, s, CH ), 2.41 (2H, s, CH ), 1.10 (6H, s,
2
2
enone), 1580, 1449, 1424, 1323, 1258, 1144, 1005, 936,
2
4
3
2
£CH ); IR (KBr) 3005 (br OH), 2957, 2872, 1635 (CvO,
3
1
1. (a) Lee, Y. R.; Suk, J. Y. Tetrahedron Lett. 2000, 41, 4795. (b)
Lee, Y. R.; Suk, J. Y.; Kim, B. S. Tetrahedron Lett. 1999, 40,
8219. (c) Lee, Y. R.; Suk, J. Y.; Kim, B. S. Tetrahedron Lett.
2
1
13
9
9
4
14 cm
;
7.55, 46.77, 31.31, 27.34. Anal. calcd for C H BrO : C,
C NMR (75 MHz, CDCl þDMSO-d6) d
3
8
11
2
3.86; H, 5.06. Found: C, 43.95; H, 4.87.
1
999, 40, 6603.
1
1
1
2. (a) Lee, Y. R.; Suk, J. Y. Chem. Commun. 1998, 2621. (b) Lee,
Y. R.; Kim, D. H. Tetrahedron Lett. 2001, 42, 6561.
3. Taber, D. F.; Ruckle, R. E., Jr.; Hennessy, M. J. Org. Chem.
1986, 51, 4077.
3
.4.8. 3-Hydroxy-2-iodo-5,5-dimethylcyclohex-2-enone
(
(
65). Reaction of 4 (166 mg, 1.0 mmol) and ethyl iodide
2 mL) under Rh (OAc) (2.2 mg) afforded 65 (247 mg,
2
4
93%) as a solid; mp 166–1678C (from hexane–ethyl
1
acetate); H NMR (300 MHz, CDCl ) d 6.30 (1H, s, OH),
4. Doyle, M. P.; Tamblyn, W. H.; Bagheri, V. J. Org. Chem.
1981, 46, 5094.
3
2
IR (KBr) 3003 (br OH), 2955, 2868, 1634 (CvO, enone),
.54 (2H, s, CH ), 2.42 (2H, s, CH ), 1.08 (6H, s, 2£CH );
2
2
3
15. (a) Padwa, A.; Stull, P. D. Tetrahedron Lett. 1987, 28, 5407.
b) Dean, D. C.; Krumpe, K. E.; Padwa, A. J. Chem. Soc.,
(
Chem. Commun. 1989, 921.
570, 1447, 1408, 1309, 1256, 1142, 999, 930 cm21
;
13
C
1
NMR (75 MHz, CDCl þDMSO-d ) d 76.04, 46.06, 31.47,
3
6
16. Pirrung, M. C.; Zhang, Z.; Lackey, K.; Sternbach, D. D.;
Brown, F. J. Org. Chem. 1995, 60, 2112.
2
C, 36.43; H, 4.36.
6.95. Anal. calcd for C H IO : C, 36.11; H, 4.17. Found:
8 11 2
1
7. Commercially available from Aldrich.