Efficient synthesis of 3-chloromethyl-2(5H)-furanones and 3-chloromethyl- 5,6-dihydropyran-2-ones via the PdCl2-catalyzed chlorocyclocarbonylation of 2,3- or 3,4-allenols

Article abstract of DOI:10.1021/jo8015677

(Chemical Equation Presented) A mild and efficient methodology involving PdCl₂-catalyzed chlorocyclocarbonylation of 2,3- or 3,4-allenols with CuCl₂ for the synthesis of 3-chloromethyl-2(5H)-furanones and 3-chloromethyl-5,6-dihydropyran-2-ones was developed. This reaction proceeded in a highly regioselective manner, i.e., the chlorine atom was introduced to the terminal position of the allene moiety while the lactone linkage was formed between the center carbon atom of the allene moiety and the hydroxyl oxygen, which was established by the X-ray single crystal diffraction study of γ-lactone 3p. The highly optically active 3-chloromethyl-2(5H)-furanones could be easily prepared from the readily available optically active 2,3-allenols. A mechanism for this reaction was proposed.

Full text of DOI:10.1021/jo8015677

Efficient Synthesis of 3-Chloromethyl-2(5H)-furanones and
3-Chloromethyl- 5,6-dihydropyran-2-ones via the PdCl2-Catalyzed
Chlorocyclocarbonylation of 2,3- or 3,4-Allenols
Xin Cheng,† Xuefeng Jiang,† Yihua Yu,‡ and Shengming Ma*,†
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, People’s Republic of China, and Shanghai Key
Laboratory of Functional Magnetic Resonance Imaging, Physics Department, East China
Normal UniVersity, Shanghai 200062, People’s Republic of China
masm@mail.sioc.ac.cn
ReceiVed July 16, 2008
A mild and efficient methodology involving PdCl2-catalyzed chlorocyclocarbonylation of 2,3- or 3,4-
allenols with CuCl2 for the synthesis of 3-chloromethyl-2(5H)-furanones and 3-chloromethyl-5,6-
dihydropyran-2-ones was developed. This reaction proceeded in a highly regioselective manner, i.e., the
chlorine atom was introduced to the terminal position of the allene moiety while the lactone linkage was
formed between the center carbon atom of the allene moiety and the hydroxyl oxygen, which was
established by the X-ray single crystal diffraction study of γ-lactone 3p. The highly optically active
3-chloromethyl-2(5H)-furanones could be easily prepared from the readily available optically active 2,3-
allenols. A mechanism for this reaction was proposed.
Introduction
of 2(5H)-furanones4 and 5,6-dihydropyran-2-ones.5 Our group
has also reported some methods for the synthesis of substituted
2(5H)-furanones based on the transition metal-promoted or
2(5H)-Furanones and 5,6-dihydropyran-2-ones, important
classes of oxygen-containing heterocyclic compounds, are
common structural units in natural products1 and important
intermediates in organic synthesis.2 2(5H)-Furanone-containing
compounds have been considered as potential insecticides,
bactericides, fungicides, antibiotics, anticancer agents, antiin-
flammatories, allergy inhibitors, antisoriasis agents, cyclooxy-
genase inhibitors, phospholipase A2 inhibitors, etc.3 Thus, much
attention has been focused on the efficient and diverse synthesis
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† Chinese Academy of Sciences.
‡ East China Normal University.
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10.1021/jo8015677 CCC: $40.75 2008 American Chemical Society
Published on Web 10/22/2008

PdCl2-Catalyzed Chlorocyclocarbonylation of Allenols
-catalyzed cyclization reactions of 2,3-allenoic acids/esters.6 In
addition, transition metal-catalyzed cyclocarbonylative cycliza-
tion reactions of (Z)-3-iodo-2-alkenols,7 2-bromoenals,8 (Z)-2-
iodoalkenyl aryl or alkyl ketones,9 terminal or internal propar-
gylic alcohols,10 3-aryl-2-alkynones,11 1,6-alkynals or hex-5-
ynoic acid pyridin-2-yl esters,12 terminal alkynes/H2O,13 and
4,6-di-tert-butylbenzofuran-2,3-dione/alkynes14 prove to be ef-
fective in constructing 2(5H)-furanones. However, reports
concerning the synthesis of 5,6-dihydropyran-2-ones through
metal-catalyzed cyclocarbonylation reactions are rare.15,16 In
2000, Takahashi et al.16 reported a successful cyclocarbonylation
of 2,3- or 3,4-allenols to form 2(5H)-furanones and 5,6-
dihydropyran-2-ones using a ruthenium catalyst. On the other
hand, we recently described a PdCl2-catalyzed chlorocyclocar-
bonylation of 2-alkynols for the efficient synthesis of (Z)-R-
chloroalkylidene-ꢀ-lactones.17 On the basis of these results, we
present here the regioselective chlorocyclocarbonylation of 2,3-
SCHEME 1
SCHEME 2
SCHEME 3
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or 3,4-allenols affording 3-chloromethyl-2(5H)-furanones and
3-chloromethyl-5,6-dihydropyran-2-ones, respectively.
Results and Discussion
Preparation of the Starting Materials. All of the terminal
2,3- or 3,4-allenols (1a-r or 2a-i) were synthesized by the
Crabbe´ homologation of the corresponding terminal alkynols,18
which were easily obtained via the Grignard reaction of ethynyl
magnesium bromide19 or allenyl magnesium bromide20 with
carbonyl compounds (Schemes 1 and 2). 2,3-Allenols 1s,t were
prepared from the reaction of the corresponding propargylic
bromides with aldehydes in the presence of NaI and SnCl2
(Scheme 3).21 2-Methyl-4-phenylbuta-2,3-dienol (1u) was pre-
pared by reduction of ethyl 2-methyl-4-phenyl-2,3-butadienoates
with DIBAL-H.22
Optically active (R)- or (S)-1a-d were also prepared via the
Crabbe´ reaction of the corresponding (R)- or (S)-propargylic
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1999, 40, 989.
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Chem. 1997, 62, 7295. (b) Ma, S.; Yu, S.; Yin, S. J. Org. Chem. 2003, 68,
8996.
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J. Org. Chem. Vol. 73, No. 22, 2008 8961

Cheng et al.
TABLE 1. PdCl2-Catalyzed Chlorocyclocarbonylation of
1,2-Dodecadien-4-ol 1a with CuCl2
TABLE 2. PdCl2-Catalyzed Chlorocyclocarbonylation of
1,2-Dodecadien-4-ol 1a with CuCl2 in MeCN under Different
Pressures of CO Using Different Amounts of PdCl2 and Et3N
entry
solvent
isolated yield of 3a (%)
entry PdCl2 (mol %) Et3N (equiv) CO (psi) isolated yield of 3a (%)
1
2
3
4
5
6
7
8
9
dioxane
toluene
benzene
DMF
CH2Cl2
THF
18
19
trace
0
57
65
66
66
70
1
2
3
4
5
6
3
10
5
5
5
2
2
2
2
1
3
100
60
63
55
61
59
52
100
1 atma
200
100
100
CH3CN
5
THFa
a This reaction was conducted with a balloon of CO.
CH3CNa
a 0.5 equiv of benzoquinone was added.
TABLE 3. PdCl2-Catalyzed Chlorocyclocarbonylation of Various
2,3-Allenols with CuCl2
alcohols,18b which are easily available from the kinetic enzy-
matic resolution of the corresponding racemic terminal prop-
argylic alcohols.23
Synthesis of 3-Chloromethyl-2(5H)-furanones via the
PdCl2-Catalyzed Chlorocyclocarbonylation of 2,3-Allenols.
In our initial try, the reaction of 2,3-allenol 1a failed to afford
the chlorocarbonylative cyclization reaction under the same
reaction conditions reported previously for the chlorocyclocar-
bonylation of 2-alkynols (10 mol % of PdCl2 and 5 equiv of
CuCl2).17 To our delight, when 2 equiv of Et3N were used as
the base, 18% of chlorocarbonylative cyclization product
3-chloromethyl-5-octyl-2(5H)-furanone 3a was isolated under
the action of 5 mol % of PdCl2 and 5 equiv of CuCl2 in dioxane
(entry 1, Table 1). The reaction is highly regioselective with
the chlorine being introduced to the terminal position of the
allene moiety and the lactone linkage being formed between
the center carbon atom of the allene moiety and the hydroxyl
oxygen. Further studies indicated that toluene, benzene, and
DMF are poor solvents for this reaction (entries 2-4, Table 1).
However, CH2Cl2, THF, or CH3CN all provided the product
3a in 57-66% yields (entries 5-7, Table 1). The addition of
0.5 equiv of benzoquinone24 did not improve the yield of 3a
dramatically (entries 8 and 9, Table 1).
The effects of the loading of PdCl2, the amount of Et3N, and
the pressure of CO were also examined (Table 2). The results
indicated that 5 mol % of PdCl2, 2 equiv of Et3N, and 100 psi
of CO are the best reaction conditions for this reaction (compare
the results of Table 2 with entry 7, Table 1).
Therefore, we defined Conditions A (5 mol % of PdCl2, 5
equiv of CuCl2, 2 equiv of Et3N, 100 psi of CO, CH3CN, 30-35
°C) for the chlorocyclocarbonylation of 2,3-allenols (entry 7,
Table 1). It should be noted that the reaction did not afford
other cyclization products as judged from the 1H NMR spectrum
of the crude reaction mixture under the standard conditions.
To investigate the scope of the reaction, the chlorocyclocar-
bonylation of various 2,3-allenols 1 was conducted under
Conditions A and the results are summarized in Table 3. Both
secondary and tertiary alcohols afforded the products in moder-
entry substrate 1
R1
R2 time (h) isolated yield of 3a (%)
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
n-C8H17
n-C7H15
n-C6H13
n-C5H11
PhCH2CH2
PhCH2
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
1
1
1
1
1
1
1
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
66 (3a)
65 (3b)
66 (3c)
69 (3d)
74 (3e)
70 (3f)
70 (3g)
62 (3h)
66 (3i)
67 (3j)
69 (3k)
70 (3l)
65 (3m)
66 (3n)
50 (3o)
59 (3p)
24 (3q)
42 (3r)
7
8
9
1g
1h
1i
cyclohexyl
Ph
4-FC6H4
4-ClC6H4
4-BrC6H4
1-naphthyl
2-ClC6H4
2,6-Cl2C6H3
4-EtC6H4
-(CH2)5-
-(CH2)4-
Ph
10
11
12
13
14
15
16
17
18
1j
1k
1l
1m
1n
1o
1p
1q
1r
1
Me
1
a For entries 1-7 and 16-18 the eluent ) petroleum ether and ethyl
ether or ethyl acetate (10:1); for entries 8-15 the eluent ) dichloromethane
and petroleum ether (5:1).
ate to good yields with the 2- and 4-position substituents all
being hydrogen. R1 may be an alkyl group, benzyl, or an aryl
group and R2 can be hydrogen or an alkyl group. To our
disappointment, under identical conditions, 2-substituted, 4-non-
substitued, or 2,4-disubstituted 2,3-allenols such as 1s-u failed
to undergo this transformation although the starting materials
were completely consumed. It should be pointed out that the
yields of products 3h-o with R1 ) aryl and R2 ) hydrogen
were dramatically decreased when petroleum ether and ethyl
ether or ethyl acetate (10:1) were used as the eluents for flash
chromatography on silica gel. However, when a mixture of
CH2Cl2 and petroleum ether was used as the eluent, the isolated
yield of 3k was improved (Table 4). Compounds 3a-g and
3p-r were isolated by using petroleum ether and ethyl ether
or ethyl acetate (10:1) as the eluents for flash chromatography
without any difficulty. In addition, the substrate 1o having an
electron-donating ethyl group at the para position of the aromatic
ring afforded the corresponding product 3o in somewhat lower
(23) (a) Xu, D.; Li, Z.; Ma, S. Chem. Eur. J. 2002, 21, 5012. (b) Xu, D.; Li,
Z.; Ma, S. Tetrahedron: Asymmetry 2003, 14, 3657. (c) Xu, D.; Li, Z.; Ma, S.
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2097.
8962 J. Org. Chem. Vol. 73, No. 22, 2008

PdCl2-Catalyzed Chlorocyclocarbonylation of Allenols
TABLE 4. PdCl2-Catalyzed Chlorocyclocarbonylation of 1k with
CuCl2 Using Different Eluents for Flash Chromatography
TABLE 6. PdCl2-Catalyzed Chlorocyclocarbonylation of Various
3,4-Allenols with CuCl2
entry
eluent for flash chromatography
isolated yield of 3k (%)
entry
substrate 2
R1
product 4
isolated yield (%)
1a
2b
3b
4b
5b
6b
DCM/PE)1:1
DCM/PE)2:1
DCM/PE)3:1
DCM/PE)4:1
DCM/PE)5:1
DCM/PE)6:1
34
53
64
68
69
68
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
Ph
4a
4b
4c
4d
4e
4f
4g
4h
4i
53
46
55
54
55
43
53
30
23
4-EtC6H4
4-ClC6H4
2-ClC6H4
4-BrC6H4
4-PriC6H4
1-naphthyl
n-C8H17
a Reaction mixture was filtrated through a short column of silica gel
before being subjected to flash chromatography on silica gel. b Reaction
mixture was evaporated directly before being subjected to flash
chromatography on silica gel.
n-C5H11
5). Further studies showed that dioxane, DMF, and Et3N are
all poor solvents for this reaction (entries 5-7, Table 5). When
THF was used as the solvent, the yield was improved to 48%
(entry 8, Table 5). When benzoquinone (0.5 equiv.), which has
been extensively used for the oxidation of Pd(0) to Pd(II) under
acidic conditions,24 was added to the reaction mixture, the yield
of product was slightly improved to 53% (compare entry 10
with entry 8, Table 5). With more benzoquinone no further
improvement of the yield was observed (entry 11, Table 5).
Thus, we defined Conditions B (5 mol % of PdCl2, 5 equiv of
CuCl2, 2 equiv of Et3N, 100 psi of CO, 0.5 equiv of benzo-
quinone, THF, 30-35 °C) for the chlorocyclocarbonylation of
3,4-allenols (entry 10, Table 5). It should be noted that the
reaction did not afford other cyclization products as judged from
the 1H NMR spectrum of the crude reaction mixture under the
standard conditions.
Some typical results for the chlorocyclocarbonylation of 3,4-
allenols are listed in Table 6. Similar to the results of
2,3-allenols, 1-substituted 3,4-allenols 2a-i underwent the
cyclocarbonylation smoothly and highly regioselectively to
afford 3-chloromethyl-5,6-dihydropyran-2-ones 4a-i in moder-
ate yields (entries 1-9, Table 6). The substrates 2h,i having
alkyl groups at the 1-position afforded the corresponding
products 4h,i in much lower yields as compared to the reaction
of substrates 2a-g with aryl groups at the same position.
Preparation of Optically Active 3-Chloromethyl-2(5H)-
furanones. With the successful chlorocyclocarbonylation pro-
tocol for the synthesis of 3-chloromethyl-2(5H)-furanones in
hand, further studies were conducted to see the possibility of
synthesizing optically active 3-chloromethyl-2(5H)-furanones
under the established Conditions A. Some typical results are
summarized in Table 7. From Table 7, it can be concluded that
racemization of the chiral center in (R)- or (S)-3 was not
observed with the yields ranging from 64% to 70%.
NMR Spectra. In the light of X-ray single crystal diffraction
analysis of compound 3p, we established the structure of the
products obtained from this PdCl2-catalyzed chlorocyclocarbo-
nylation of 2,3- or 3,4-allenols. However, there are some
noteworthy characteristics in the NMR spectra of products 3
and 4. The related information is available in the Supporting
Information.
TABLE 5. PdCl2-Catalyzed Chlorocyclocarbonylation of
1-Phenyl-3,4-pentadien-1-ol 2a with CuCl2
PdCl2 CO
base
additive
time isolated yield
entry (mol %) (psi) (equiv)
(equiv) solvent (h)
of 4a (%)
1
2
3
4
10
5
5
10
10
10
10
5
300
THF
4
1
2
3
2
2
2
1
1
1
1
complicated
100 Et3N (2)
60 NaOAc (3)
60 NaOAc (3)
60 NaOAc (3)
60 NaOAc (3)
60
100 Et3N (2)
100 Et3N (2)
100 Et3N (2)
100 Et3N (2)
CH3CN
CH3CN
HOAc
dioxane
DMF
35
35
33
NR
0
NR
48
50
53
53
5a
6b
7a
8
Et3N
THF
9
10
11
5
5
5
BQc (0.1) THF
BQ (0.5) THF
BQ (1.0) THF
a Compound 2a was not completely consumed. b No 2a was left. c BQ
is an abbreviation for benzoquinone.
yield (entry 15, Table 3) as compared to substrates 1h-n (entries
8-14, Table 3). The reaction of 1q with a five-membered ring
afforded the corresponding product 3q in 24% yield probably
due to its instability. The butenolide structures of products 3
and the regioselectivity were established by the single crystal
X-ray diffraction study of 3p (see Figure S6 in the Supporting
Information).25
Synthesis of 3-Chloromethyl-5,6-dihydropyran-2-ones via
the PdCl2-Catalyzed Chlorocyclocarbonylation of 3,4-Alle-
nols. Stimulated by the above successful results, we wanted to
expand the current reaction from 2,3-allenols to 3,4-allenols.
Again, the reaction of 3,4-allenol 2a failed to afford the
chlorocarbonylative cyclization reaction under the same reaction
conditions reported previously for the chlorocyclocarbonylation
of 2-alkynols (entry 1, Table 5).17 Gratifyingly, under Conditions
A successfully applied for the 2,3-allenols, pyran-2-one 4a was
obtained in 35% yield (entry 2, Table 5). No improvement of
yield was observed when NaOAc was used as the base instead
of Et3N (entry 3, Table 5). When HOAc was used instead of
CH3CN as the solvent, the yield dropped slightly (entry 4, Table
Mechanistic Considerations. A rationale for the PdCl2-
catalyzed regioselective chlorocyclocarbonylation of 2,3- or 3,4-
allenols is shown in Scheme 4. The selective coordination of
the terminal double bond in 1 or 2 with PdCl2 gives coordination
(25) For the crystal data and ORTEP representation of compound 3p, see
the Supporting Information.
J. Org. Chem. Vol. 73, No. 22, 2008 8963

Cheng et al.
TABLE 7. Synthesis of Optically Active 3-Chloromethyl-
5H-furan-2-ones
SCHEME 4
elimination of M3 or M4 affords 3 or 4 and Pd(0), which is
oxidized with oxidant to regenerate the catalytically active
species PdCl2.
Conclusion
In summary, we have developed a mild and efficient
methodology for the regioselective synthesis of 3-chloromethyl-
2(5H)-furanones and 3-chloromethyl-5,6-dihydropyran-2-ones
in moderate to good yields. The key step of this reaction may
involve the highly regioselective chlorometalation of PdCl2 with
the terminal double bond in allenols by introducing the chlorine
atom to the terminal position of the allene moiety, which has
similar regioselectivity as in the copper(I) chloride-mediated
carbometalation of 2,3-allenols with Grignard reagents reported
recently by our group.26c Highly optically active 3-chloromethyl-
2(5H)-furanones can be easily formed from the readily available
optically active 2,3-allenols. Further studies in this area are being
conducted in our laboratory.
Experimental Section
PdCl2-Catalyzed Chlorocyclocarbonylation of 2,3-Allenols
in the Presence of CuCl2. Preparation of 3-Chloromethyl-2(5H)-
furanones 3a-g and 3p-r. Typical Procedure I (Conditions
A): Synthesis of 3-Chloromethyl-5-octyl-2(5H)-furanone (3a).
2,3-Allenol 1a (92 mg, 0.50 mmol), anhydrous CuCl2 (336 mg,
2.50 mmol), PdCl2 (5 mg, 0.028 mmol), CH3CN (6 mL), and Et3N
(102 mg, 1.01 mmol) were added sequentially to a glass vessel
containing a stirring bar placed in a stainless-steel autoclave with
stirring. The autoclave was flushed three times with 150 psi of CO
gas. The autoclave was then charged with 100 psi of CO gas. After
the mixture was stirred for 1 h at 30-35 °C (oil bath), the excess
CO gas was ventilated, and the residue was diluted with Et2O.
Filtration through a short column of silica gel, evaporation, and
flash chromatography on silica gel (eluent: petroleum ether/ethyl
1
a Isolated yield. b ee value was determined by HPLC. c The reaction
was carried out under Conditions B.
ether ) 10:1) afforded 82 mg (66%) of 3a: liquid; H NMR (500
MHz, CDCl3) δ 7.40 (q, J ) 1.8 Hz, 1 H), 5.00-4.94 (m, 1 H),
4.22 (t, J ) 1.8 Hz, 2 H), 1.80-1.69 (m, 1 H), 1.68-1.60 (m, 1
H), 1.49-1.16 (m, 12 H), 0.85 (t, J ) 7.0 Hz, 3 H); 13C NMR
(75.4 MHz, CDCl3) δ 171.0, 152.0, 130.8, 81.6, 35.9, 33.0, 31.6,
29.2, 29.1, 29.0, 24.8, 22.5, 14.0; MS (EI) m/z (%) 246 (M+(37Cl),
2.10), 244 (M+(35Cl), 5.11), 57 (100); IR (neat) 2927, 1761, 1653,
1466, 1341, 1087 cm-1; HRMS (EI) calcd for C13H21O235Cl (M+)
244.1230, found 244.1232.
complex M1, which is followed by the highly regioselective
chlorometalation to give the cyclic vinylic intermediate M2 by
introducing the chlorine atom to the terminal position of the
allene moiety.26 Subsequent coordination and insertion of CO
affords metallocyclic intermediates M3 or M4. Reductive
Preparation of 3-Chloromethyl-2(5H)-furanones 3h-o. Com-
pounds 3h-o were synthesized following typical procedure I except
that the reaction time was reduced to 0.5 h, the reaction mixture
was evaporated directly before being subjected to flash chroma-
(26) (a) Lu, Z.; Ma, S. J. Org. Chem. 2006, 71, 2655. (b) Ma, S.; Lu, Z.
AdV. Synth. Catal. 2006, 348, 1894. (c) Lu, Z.; Ma, S. AdV. Synth. Catal. 2007,
349, 1225. (d) Lu, Z.; Chai, G.; Ma, S. J. Am. Chem. Soc. 2007, 129, 14546.
8964 J. Org. Chem. Vol. 73, No. 22, 2008

PdCl2-Catalyzed Chlorocyclocarbonylation of Allenols
tography on silica gel, and the eluent used for flash chromatography
is a 5:1 mixture of dichloromethane and petroleum ether.
×
37Cl), 0.85), 258 (M+(37Cl, 35Cl), 4.33), 256 (M+(2 × 35Cl),
6.40), 116 (100); IR (neat) 3066, 2964, 1728, 1596, 1574, 1479,
1378, 1234, 1122 cm-1. Anal. Calcd for C12H10O2Cl2: C, 56.06;
H, 3.92. Found: C, 55.94; H, 3.80.
PdCl2-Catalyzed Chlorocyclocarbonylation of 3,4-Allenols
in the Presence of CuCl2. Preparation of 3-Chloromethyl-5,6-
dihydropyran-2-ones 4a-i. Typical Procedure II (Conditions
B): Synthesis of 3-Chloromethyl-6-(2′-chlorophenyl)-5,6-dihy-
dropyran-2-one (4d). 3,4-Allenol 2d (197 mg, 1.01 mmol),
anhydrous CuCl2 (672 mg, 5.00 mmol), PdCl2 (9 mg, 0.051
mmol), benzoquinone (54 mg, 0.50 mmol), THF (12 mL), and
Et3N (202 mg, 2.00 mmol) were added sequentially to a glass
vessel containing a stirring bar placed in a stainless-steel
autoclave with stirring. The autoclave was flushed three times
with 150 psi of CO gas. The autoclave was then charged with
100 psi of CO gas. After the mixture was stirred for 1 h at 30-35
°C (oil bath), the excess CO gas was ventilated, and the residue
was diluted with Et2O. Filtration through a short column of silica
gel, evaporation, and flash chromatography on silica gel (eluent:
dichloromethane/petroleum ether ) 1:1) afforded 141 mg (54%)
of 4d: solid; mp 102-104 °C (petroleum ether/ethyl acetate);
1H NMR (500 MHz, CDCl3) δ 7.64 (dd, J ) 7.5 and 1.5 Hz, 1
H), 7.40-7.28 (m, 3 H), 7.13-7.07 (m, 1 H), 5.84 (dd, J )
12.2 and 3.8 Hz, 1 H), 4.41 (dm, J ) 13.0 Hz, 1 H), 4.34 (dm,
J ) 13.0 Hz, 1 H), 2.89 (ddd, J ) 18.5, 6.3, and 3.8 Hz, 1 H),
2.56 (ddq, J ) 18.5, 12.2, and 2.2 Hz, 1 H); 13C NMR (75.4
MHz, CDCl3) δ 163.2, 142.4, 135.7, 131.2, 129.6, 129.5, 129.1,
127.34, 127.32, 76.0, 41.1, 30.5; MS (EI) m/z (%) 260 (M+(2
Synthesis of (5R)-3-Chloromethyl-5-octyl-2(5H)-furanone ((5R)-
(3a)) Following Typical Procedure I. The reaction of (R)-1a (182
mg, 1.00 mmol, >99% ee), anhydrous CuCl2 (673 mg, 5.01 mmol),
PdCl2 (9 mg, 0.051 mmol), and Et3N (202 mg, 2.00 mmol) in 12
mL of CH3CN afforded 172 mg (70%) of (5R)-3a with 99% ee as
determined by HPLC analysis (Chiralcel OJ-H, n-hexane:i-PrOH
) 90:10, 0.7 mL/min, 214 nm), tr 12.5 (minor), 14.0 (major); [R]20
-32.9 (c 1.05, CHCl3).
D
Acknowledgment. Financial support from the Major State
BasicResearchDevelopmentProgram(GrantNo.2006CB806105),
National Natural Science Foundation of China (Nos. 20732005
and 20423001), and Shanghai Municipal Committee of Science
and Technology is greatly appreciated.
Supporting Information Available: General procedures and
analytical data for compounds 1, 2, 3, and 4, 1H and 13C NMR
spectra of these compounds, and CIF file of 3p. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO8015677
J. Org. Chem. Vol. 73, No. 22, 2008 8965