Oxidative addition of chloro- and dichloroacetic acid to alkenes to give α-chloro- and α,α-dichlorobutyrolactones with manganese(III) acetate

Article abstract of DOI:10.3987/com-03-s(p)11

Oxidative addition of chloroacetic acid and dichloroacetic acid to alkenes with Mn(OAc)₃ to give α-chloro- and α,α -dichlorobutyrolactones proceeds in moderate to good yield in MeCN containing one equivalent of the sodium salt of the carboxylic

Full text of DOI:10.3987/com-03-s(p)11

HETEROCYCLES, Vol. 62, 2004, pp. 325 - 332
Received, 13th June, 2003, Accepted, 25th July, 2003, Published online, 16th September, 2003
OXIDATIVE ADDITION OF CHLORO- AND DICHLOROACETIC ACID
TO ALKENES TO GIVE α-CHLORO- AND α,α-DICHLORO-
BUTYROLACTONES WITH MANGANESE(III) ACETATE†
Barry B. Snider* and Qinglin Che
Department of Chemistry MS 015, Brandeis University, Waltham, MA
02454-9110, USA e-mail: snider@brandeis.edu
Abstract – Oxidative addition of chloroacetic acid and dichloroacetic acid to
alkenes with Mn(OAc)3 to give α-chloro- and α,α-dichlorobutyrolactones
proceeds in moderate to good yield in MeCN containing one equivalent of the
sodium salt of the carboxylic acid.
INTRODUCTION
The reaction of alkenes with 2 equivalents of Mn(OAc)3 in AcOH at reflux to give lactone (1) (see equation
1) first reported by Bush and Finkbeiner, and Heiba and Dessau is a versatile method for the annulation of a
γ-lactone to an alkene.1-3 The rate determining step in the reaction is the loss of a proton from
manganese(III) acetate (2) to give enolate (3) (see equation 2).4 Rapid loss of Mn(II) gives radical (4),
which adds to the alkene to give radical (5). Oxidation of 5 with loss of Mn(II) gives lactone (1).
O
Mn(OAc)3
AcOH, reflux
H2C
(1)
O
R
R
1
Since enolization is the slow step, acids with a more acidic α-proton should be more reactive than acetic
acid. Exchange of R1R2CHCO2H with Mn(OAc)3 should give Mn(III) carboxylate (6). Loss of a proton
from 6 to give enolate (7) should be faster than loss of a proton from acetate (2) to give enolate (3). Enolate
(7) will rapidly lose Mn(II) to give radical (8), which will add to the alkene to give radical (9), which will be
oxidized with loss of Mn(II) to give α-substituted lactone (10). Acids with much more acidic α-protons
† Dedicated to Professor Leo Paquette on the occasion of his 70th birthday

Mn(III)
H2C
O
O
O
fast
H2C
H3C
O
-Mn(II)
O
R
•H2C
slow
-H+
Mn(III)
Mn(III)
O
Mn(III)
O
•
O
-Mn(II)
O
O
Mn(III)
R
R
2
3
1
4
5
(2)
R1R2CHCO2H
AcOH
R1
Mn(III)
H2C
R1
C
2R1 O
R1 O
R1
R
R2
O
fast
CH
R2
O
-Mn(II)
O
R
C•
R2
slow
R2
Mn(III)
O
Mn(III)
O
Mn(III)
-H+
-Mn(II)
O
•
O
O
Mn(III)
R
R
6
7
9
10
8
such as cyanoacetic acid and ethyl hydrogen malonate add to alkenes in acetic acid at 23-70 ºC.5,6 However,
acids with only slightly more acidic α-protons such as chloroacetic and 3-chloropropanoic acid do not
enolize enough faster to compete with enolization of the solvent, acetic acid. For instance, the alpha proton
of chloroacetic acid is 1,000 times more acidic than the alpha proton of acetic acid, but chloroacetic acid
reacts with Mn(OAc)3 only 11 times faster than acetic acid.4a Lactone (11) can be formed by the reaction of
other carboxylic acids with alkenes and Mn(OAc)3 in moderate yield if a large excess of the carboxylic acid
is used as the solvent (see equation 3).1,5 The need to use a vast excess of the carboxylic acid as the solvent
has limited the utility of this route to α-substituted lactones (11).
Mn(OAc)3
O
R1
R1CH2CO2H
H2C
(3)
100-120 °C
O
R
11, R1 = Me, Cl or CH2Cl
R
(excess
R1CH2CO2H
as solvent)
During the course of our study of Mn(III)-based oxidative free-radical cyclizations, we found that many
solvents other than acetic acid can be used for these reactions.7 We decided to explore whether the
oxidative addition of dichloroacetic and chloroacetic acid to alkenes with Mn(OAc)3 to give
α,α-dichlorolactones (12) and α-chlorolactones (13) could be carried in an inert solvent without the need to
use excess carboxylic acid as solvent. Lactones (12) and (13) have been previously prepared in moderate
yield by radical reactions of trichloroacetic or dichloroacetic acid and esters to alkenes initiated by CuCl,
[CpMo(CO)3]2, or (Ph3P)3RuCl2 at high temperatures.8
RESULTS AND DISCUSSION
As expected, reaction of 1-hexene, 1 equivalent of dichloroacetic acid and 2 equivalents of
Mn(OAc)3•2H2O in AcOH at 85 ºC for 2 days afforded 24% of lactone (1) and only 6% of the desired
lactone (12a) (see equation 4). Even though the alpha proton of dichloroacetic acid is more acidic than that

of acetic acid,9 1 is still the major product since acetic acid is present in such great excess as solvent. No
lactone (12a) was formed from 1-hexene, dichloroacetic acid, and anhydrous Mn(OAc)310 in EtOH, DMF,
trifluoroethanol, benzene, or 9:1 MeCN/TFA at 70-100 ºC.
O
O
Cl
Cl
Mn(OAc)3
solvent
(4)
O
+
O
Cl2CHCO2H + 1-hexene
Bu
Bu
12a
1
Finally, we were pleased to find that lactone (12a) was formed in 33% yield from 1-hexene, 2 equivalents
of dichloroacetic acid and 2 equivalents of anhydrous Mn(OAc)3 in MeCN at 95 ºC in a sealed tube for 3
days. No lactone (1) was formed in MeCN. The yield of 12a decreased from 33% to 28% with
Mn(OAc)3•2H2O. Addition of one equivalent of sodium dichloroacetate to the reaction mixture increased
the yield of 12a to 45% and decreased the time required for consumption of Mn(III) to 1.5 days. The yield
a
Table 1. Preparation of α,α-Dichlorobutyrolactones (12)
b
Entry
Alkene
Time
40 h
Product
Yield
O
O
H
45%
a
12a
Cl
n-Bu
Cl
n-Bu
O
O
43 h
48 h
b
c
Cl
12b
12c
H
48%
n-Hex
Cl
O
n-Hex
O
Cl
62%
Ph
H
Cl
(90%)
Ph
O
Et
Et
O
46 h
40 h
48 h
d
e
Cl
Et
Et
12d
12e
36%
Cl
O
Me
Ph
O
Me
Ph
81%
Cl
Cl
(96%)
O
Ph
Ph
O
82%
(95%)
12f
Cl
Ph
Ph
f
Cl
O
O
Cl
Cl
27%
12g
12h
48 h
30 h
g
h
O
Me
O
30%
(73%)
c
Cl
Cl
Ph
Ph
Me
a
A 0.1 M solution of alkene in MeCN containing 1 equiv. of Cl2HCCO2Na,
and 2 equiv. of Cl2CHCO2H and Mn(OAc)3 was heated in a sealed tube
b
at 95-100 °C for the indicated time. Isolated yield. Yield in parentheses
c
is based on reacted alkene. 26:1 trans/cis mixture.

of 12a decreased from 45% to 22% with three equivalents of sodium dichloroacetate. No lactone (12a) was
formed from two equivalents of sodium dichloroacetate in the absence of dichloroacetic acid. This
suggests that the 2:1 mixture of dichloroacetic acid to sodium dichloroacetate provides near optimal pH for
lactone formation.
These optimized conditions were then used to survey the scope of the reaction with regard to the alkene as
shown in Table 1. α,α-Dichlorolactones (12) were obtained in 27-82% yield. As expected for an
electrophilic radical, MnO2CCCl2•, the reactions proceed in 62-82% yield with nucleophilic alkenes in
which one end is unsubstituted and therefore sterically accessible and the other end has a phenyl substituent
(Entries c, e, and f). Terminal and 1,1-disubstituted alkyl substituted alkenes afford 27-48% of lactone (12)
(Entries a, b, d, and g). With the exception of β-methylstyrene (Entry h), internal alkenes give poor yields
of lactone (12). The structures were assigned by comparison with authentic samples.8 The stereochemistry
of lactone (12h) was assigned based on vicinal coupling constants for the trans (9.8 Hz) and cis (5.5 Hz)
isomers.11
We also briefly investigated the reactions of alkenes with five equivalents of chloroacetic acid, two
equivalents of Mn(OAc)3 and one equivalent of sodium chloroacetate in acetonitrile (see equation 5).
Although, consumption of Mn(III) was complete in 5-12 h, the yield of α-chlorobutyrolactones (13a-c)
was lower than for the analogous α,α-dichlorobutyrolactone (12). The structures were assigned by
comparison with authentic samples.6b,8
O
O
Cl
OH
Mn(OAc)3 (2eq)
Cl
O
(5)
R1
R2
ClCH2CO2Na (1eq)
CH3CN, 85-90°C, 5-12 h
R1
R2
13a, R1 = H, R2 = n-Bu (22%, 1:1 trans/cis)
13b, R1 = H, R2 = Ph (58%, 1:1 trans/cis)
13c, R1 = R2 = Ph (38%, 84% based on recoved Ph2C=CH2)
In conclusion, we have shown that oxidative addition of chloroacetic acid and dichloroacetic acid to a
variety of alkenes to give dichlorolactones (12) and chlorolactones (13), respectively, can be successfully
carried out with Mn(OAc)3 and one equivalent of the sodium salt of the acid in MeCN at 85-100 °C.
EXPERIMENTAL
General. All reactions were performed in oven-dried resealable tubes. NMR spectra were recorded at 400
MHz in CDCl3. Chemical shifts are reported in δ and coupling constants in Hz. IR spectra were reported in
cm-1. Anhydrous Mn(OAc)3 was prepared from commercial Mn(OAc)3·2H2O (Fisher) by drying over P2O5
for 1 week under vacuum.10

5-Butyl-3,3-dichlorodihydro-2(3H)-furanone (12a). NaO2CCHCl2 (75.5 mg, 0.5 mmol) and anhydrous
Mn(OAc)3 (232 mg, 1 mmol) were added to 5 mL of dry MeCN in a resealable tube at rt. Cl2CHCO2H (128
mg, 1 mmol) and 1-hexene (42 mg, 0.5 mmol) were added to the suspension under nitrogen. After sealing,
the tube was immersed in an oil bath at 95-100 °C. The reaction was stirred magnetically at this
temperature until the brown color of Mn(III) disappeared (40 h). Upon cooling to rt, the reaction mixture
was diluted with water (10 mL) and extracted with CH2Cl2 (3 × 10 mL). The combined organic extracts
were washed with saturated NaHCO3 solution, water, and brine, dried (Na2SO4) and concentrated under
reduced pressure. The crude product was purified by flash chromatography (silica gel, 50:1
1
hexanes/EtOAc) to give 48 mg (45%) of lactone (12a) as a colorless oil: H NMR 4.65-4.61 (m, 1H), 3.17
(dd, 1H, J = 14.1, 4.9), 2.61 (dd, 1,H J = 14.1, 9.7), 1.87-1.26 (m, 6H), 0.94 (t, 3H, J = 7.3); 13C NMR 167.7,
78.1, 77.5, 50.2, 33.7, 26.9, 22.2, 13.8; IR (neat) 1795. The 1H NMR spectral data are identical to those
reported previously.8b
3,3-Dichloro-5-hexyldihydro-2(3H)-furanone (12b) was prepared analogously to 12a from
NaO2CCHCl2 (76 mg, 0.5 mmol), anhydrous Mn(OAc)3 (232 mg, 1 mmol), Cl2CHCO2H (128 mg, 1 mmol)
and 1-octene (85 µL, 0.5 mmol) in 5 mL of dry MeCN. Flash chromatography (silica gel, 40:1
1
hexanes/EtOAc) of the crude product gave 70 mg (48%) of lactone (12b) as a colorless oil: H NMR 4.62
(ddt, 1H, J = 9.8, 4.9, 6.8), 3.16 (dd, 1H, J = 14.0, 4.9), 2.61 (dd, 1H, J = 14.0, 9.8), 1.87-1.28 (m, 10H),
0.89 (t, 3H, J = 7.3); 13C NMR 167.8, 78.1, 77.5, 50.2, 34.1, 31.5, 28.7, 24.8, 22.4, 14.0; IR (neat) 1795.
The 1H NMR spectral data are identical to those reported previously.8b
3,3-Dichlorodihydro-5-phenyl-2(3H)-furanone (12c) was prepared analogously to 12a from
NaO2CCHCl2 (76 mg, 0.5 mmol), anhydrous Mn(OAc)3 (232 mg, 1 mmol), Cl2CHCO2H (128 mg, 1 mmol)
and styrene (64 µL, 0.5 mmol) in 5 mL of dry acetonitrile. Flash chromatography (silica gel, 100:1~25:1
hexanes/EtOAc) of the crude product gave 16 mg of styrene followed by 72 mg (62%, 90% based on
1
recovered styrene) of lactone (12c) as a colorless oil: H NMR 7.45-7.34 (m, 5H), 5.62 (dd, 1H, J = 10.3,
4.9), 3.43 (dd, 1H, J = 14.6, 4.9), 2.93 (dd, 1H, J = 14.6, 10.3); 13C NMR 167.4, 135.4, 129.5, 129.0 (2 C),
1
125.7 (2 C), 78.5, 77.4, 52.2; IR (neat) 1798. The H NMR spectral data are identical to those reported
previously.8f
3,3-Dichloro-5,5-diethyldihydro-2(3H)-furanone (12d) was prepared analogously to 12a from
NaO2CCHCl2 (76 mg, 0.5 mmol), anhydrous Mn(OAc)3 (232 mg, 1 mmol), Cl2CHCO2H (128 mg, 1 mmol)
and 2-ethyl-1-butene (61 µL, 0.5 mmol) in 5 mL of dry MeCN. Flash chromatography (silica gel, 25:1
1
hexanes/EtOAc) of the crude product gave 38 mg (36%) of lactone (12d) as a colorless oil: H NMR 3.02
(s, 2H), 1.93-1.76 (m, 4H), 0.96 (t, 6H, J = 7.3); 13C NMR 168.3, 88.0, 77.4, 51.7, 30.4 (2 C), 7.6 (2 C); IR
(neat) 1791. The 1H NMR spectral data are identical to those reported previously.8d

3,3-Dichlorodihydro-5-methyl-5-phenyl-2(3H)-furanone (12e) was prepared analogously to 12a from
NaO2CCHCl2 (76 mg, 0.5 mmol), anhydrous Mn(OAc)3 (232 mg, 1 mmol), Cl2CHCO2H (128 mg, 1 mmol)
and α-methylstyrene (65 µL, 0.5 mmol) in 5 mL of dry MeCN. Flash chromatography (silica gel, 100:1 to
20:1 hexanes/EtOAc) of the crude product gave 18 mg of α-methylstyrene followed by 99 mg (81%, 96%
based on recovered α-methylstyrene) of lactone (12e) as a colorless oil: 1H NMR 7.40-7.29 (m, 5H), 3.49 (d,
1H, J = 15.0), 3.36 (d, 1H, J = 15.0), 1.83 (s, 3H); 13C NMR 167.6, 142.7, 128.7 (2 C), 128.1, 123.6 (2 C),
1
85.0, 76.7, 56.4, 30.2; IR (neat) 1797. The H NMR spectral data are identical to those reported
previously.8f
3,3-Dichlorodihydro-5,5-diphenyl-2(3H)-furanone (12f) was prepared analogously to 12a from
NaO2CCHCl2 (76 mg, 0.5 mmol), anhydrous Mn(OAc)3 (232 mg, 1 mmol), Cl2CHCO2H (128 mg, 1 mmol)
and 1,1-diphenylethylene (88 µL, 0.5 mmol) in 5 mL of dry MeCN. Flash chromatography (silica gel,
100:1 to 20:1 hexanes/EtOAc) of the crude product gave 12 mg of 1,1-diphenylethylene followed by 126
mg (82%, 95% based on recovered 1,1-diphenylethylene) of lactone (12f) as a white solid: mp 94-95 °C
(lit.,8a mp 96-98 °C); 1H NMR 7.40-7.24 (m, 10H), 3.88 (s, 2H); 13C NMR 167.2, 141.5 (2 C), 128.7(2 C),
128.4 (4 C), 124.9 (4 C), 87.4, 76.3, 55.7; IR (neat) 1791.
3,3-Dichloro-1-oxaspiro[4.4]nonan-2-one (12g) was prepared analogously to 12a from NaO2CCHCl2 (76
mg, 0.5 mmol), anhydrous Mn(OAc)3 (232 mg, 1 mmol), Cl2CHCO2H (128 mg, 1 mmol) and
methylenecyclopentane (52 µL, 0.5 mmol) in 5 mL of dry MeCN. Flash chromatography (silica gel, 50:1
1
hexanes/EtOAc) of the crude product gave 38 mg (27%) of lactone (12g) as a colorless oil: H NMR 3.14 (s,
13
2H), 2.22-2.17 (m, 2H), 1.90-1.74 (m, 6H); C NMR 167.7, 92.8, 77.5, 53.3, 39.0 (2 C), 23.6 (2 C); IR
(neat) 1790. Anal. Calcd for C8H10Cl2O2: C, 45.96; H, 4.82; Cl, 33.91. Found: C, 45.64; H, 4.57; Cl,
33.84.
3,3-Dichlorodihydro-4-methyl-5-phenyl-2(3H)-furanone (12h) was prepared analogously to 12a from
NaO2CCHCl2 (76 mg, 0.5 mmol), anhydrous Mn(OAc)3 (232 mg, 1 mmol), Cl2CHCO2H (128 mg, 1 mmol)
and trans-β-methylstyrene (65 µL, 0.5 mmol) in 5 mL of dry MeCN. Flash chromatography (silica gel,
100:1 to 20:1 hexanes/EtOAc) of the crude product gave 35 mg of trans-β-methylstyrene followed by 37
mg (30%, 73% based on recovered trans-β-methylstyrene) of lactone (12h) as a 26:1 mixture of trans and
cis isomers. Anal. Calcd for C11H10Cl2O2: C, 53.90; H, 4.11; Cl, 28.93. Found: C, 54.03; H, 3.92; Cl,
28.74.
Data for trans-12h: 1H NMR 7.45-7.33 (m, 5H), 5.04 (d, 1H, J = 9.8), 2.78 (dq, 1H, J = 9.8, 7.0), 1.29 (d,
3H, J = 7.0); 13C NMR 167.7, 134.4, 130.1, 129.3 (2 C), 126.7 (2 C), 84.8, 82.9, 55.8, 9.2; IR (neat) 1803.
Partial data for cis-12h: 1H NMR 7.45-7.33 (m, 5H), 5.93 (d, 1H, J = 5.5), 3.28 (dq, 1H, J = 7.3, 5.5), 0.87
(d, 3H, J = 7.3).

5-Butyl-3-chlorodihydro-2(3H)-furanone (13a). ClCH2CO2H (235 mg, 2.5 mmol), NaO2CCH2Cl (58
mg, 0.5 mmol) and anhydrous Mn(OAc)3 (232 mg, 1 mmol) were added to 5 mL of dry MeCN in a
resealable tube at rt. 1-Hexene (42 mg, 0.5 mmol) was added to the suspension via syringe under nitrogen.
After sealing, the tube was immersed in an oil bath at 85-90 °C. The reaction was stirred at this temperature
until the brown color of Mn(III) disappeared (5 h). Upon cooling to rt, the reaction mixture was diluted
with water (10 mL) and extracted with CH2Cl2 (3 × 10 mL), the combined organic extracts were washed
with saturated NaHCO3 solution, water, and brine, dried (Na2SO4) and concentrated under reduced pressure.
The crude product was purified by flash chromatography (silica gel, 50:1 hexanes/EtOAc) to give 20 mg
(22%) of lactone (13a) as a 1:1 mixture of trans and cis isomers.8d
Data for trans-13a: 1H NMR 4.79-4.72 (m, 1H), 4.43 (dd, 1H, J = 6.7, 2.5), 2.52 (ddd, 1H, J = 14.1, 5.6, 2.5),
2.31 (ddd, 1H, J = 14.1, 8.5, 6.7), 1.88-1.25 (m, 6H), 0.93 (t, 3H, J = 7.0); IR (neat) 1791.
Data for cis-13a: 1H NMR 4.54 (dd, 1H, J = 10.4, 8.5), 4.48-4.40 (m, 1H), 2.92 (ddd, 1H, J = 12.7, 8.5, 6.1),
2.13 (ddd, 1H, J = 12.7, 10.4, 9.8), 1.88-1.25 (m, 6H), 0.93 (t, 3H, J = 7.0); IR (neat) 1791.
3-Chlorodihydro-5-phenyl-2(3H)-furanone (13b) was prepared analogously to 13a from ClCH2CO2H
(235 mg, 2.5 mmol), NaO2CCH2Cl (58 mg, 0.5 mmol), anhydrous Mn(OAc)3 (232 mg, 1 mmol) and
styrene (64.3 µL, 0.5 mmol) in 5 mL of dry MeCN for 9 h. Flash chromatography (silica gel, 25:1
hexanes/EtOAc) gave 57 mg (58%) of lactone (13b) as a 1:1 mixture of trans and cis isomers.
Data for trans-13b: 1H NMR 7.45-7.34 (m, 5H), 5.76 (dd, 1H, J = 8.6, 6.1), 4.50 (dd, 1H, J = 6.7, 2.5), 2.81
(ddd, 1H, J = 14.3, 6.1, 2.5), 2.63 (ddd, 1H, J = 14.3, 8.6, 6.7); IR (neat) 1791. The 1H NMR spectral data
are identical to those reported previously.8e,8f
Data for cis-13b: 1H NMR 7.45-7.34 (m, 5H), 5.43 (dd, 1H, J = 9.8, 5.5), 4.71 (dd, 1H, J = 11.0, 8.6), 3.20
(ddd, 1H, J = 13.6, 8.6, 5.5), 2.44 (ddd, 1H, J = 13.6, 11.0, 9.8,); IR (neat) 1791. The 1H NMR spectral data
are identical to those reported previously.8e,8f
3-Chlorodihydro-5,5-diphenyl-2(3H)-furanone (13c) was prepared analogously to 13a from
ClCH2CO2H (235 mg, 2.5 mmol), NaO2CCH2Cl (58 mg, 0.5 mmol), anhydrous Mn(OAc)3 (232 mg, 1
mmol) and 1,1-diphenylethylene (88 µL, 0.5 mmol) in 5 mL of dry MeCN for 12 h. Flash chromatography
(silica gel, 100:1~25:1 hexanes/EtOAc) gave 50 mg of 1,1-diphenylethylene followed by 52 mg (38%, 84%
6b
based on recovered 1,1-diphenylethylene) of lactone (13c) as a white solid: mp 90-92 °C (lit.,
mp
90.0-91.4 °C); 1H NMR 7.43-7.29 (m, 10H), 4.51 (dd, 1H, J = 8.0, 11.0), 3.61 (dd, 1H, J = 8.0, 13.5), 3.03
(dd, 1H, J = 11.0, 13.5); 13C NMR 171.3, 142.3, 141.2, 128.9 (2 C), 128.7 (2 C), 128.4, 128.3, 125.2 (4 C),
87.6, 51.2, 45.5; IR (neat) 1791. The 1H NMR spectral data are identical to those reported previously.6b
ACKNOWLEDGEMENTS
We thank the National Institutes of Health (GM-50151) for financial support.

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1,1-dichloroacetone is 11: J. P. Guthrie, Can. J. Chem., 1979, 57, 1177.
10. N. K. Dunlap, M. R. Sabol, and D. S. Watt, Tetrahedron Lett., 1984, 25, 5839.
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