Facile synthesis of aliphatic esters, malonates and phenylsulfonyl esters using copper-catalyzed addition of methallyl grignard reagent to activated cyclopropanes

Article abstract of DOI:10.1055/s-2001-9751

Copper-mediated conjugate addition of allylic Grignard reagents to activated cyclopropane derivatives was studied. Unsaturated esters, malonates and phenylsulfonyl esters 2a-d were synthesized from the respective cyclopropanes 1a-d and methallylmagnesium

Full text of DOI:10.1055/s-2001-9751

PAPER
145
Facile Synthesis of Aliphatic Esters, Malonates and Phenylsulfonyl Esters
Using Copper-Catalyzed Addition of Methallyl Grignard Reagent to Activated
Cyclopropanes
Igor Prowotorow, Jerzy Wicha,*a Koichi Mikamib
a Institute of Organic Chemistry, Polish Academy of Sciences, POB 58, PL 01-224 Warsaw 42, Poland
Fax +48(22)6326681; E-mail: jwicha@ichf.edu.pl
b Tokyo Institute of Technology, Department of Chemical Technology, Meguro, Tokyo 152, Japan
Received 26 July 2000; revised 31 August 2000
propanes as a source of four or five carbon unit
Abstract: Copper-mediated conjugate addition of allylic Grignard
[CH2CH2CH2CO2R or CH2CH2CH(CO2R)2] in the syn-
reagents to activated cyclopropane derivatives was studied. Unsat-
thesis of higher aliphatic esters or malonates by a “homol-
urated esters, malonates and phenylsulfonyl esters 2a-d were
ogous” Michael addition reaction involving Grignard
reagents. For our work 1,1-dialkoxycarbonyl, 1-alkoxy-
carbonyl-1-phenylsulfonyl cyclopropane derivatives
1a-e (Scheme 1) and methallyl magnesium chloride were
chosen.
synthesized from the respective cyclopropanes 1a-d and methallyl-
magnesium chloride.
Key words: cyclopropanes, Grignard reagents, 1,5-addition,
copper, esters
Treatment of di-tert-butyl ester 1a with methallylmagne-
sium chloride (2 mol equiv) and CuI◊Me2S (0.4 mol
equiv) in THF at -30 °C to -20 °C afforded smoothly the
1,5-addition product 2a (Table). No traces of the respec-
tive 1,2-addition product 3a could be detected (a sample
of 3a was prepared by reaction of 1a and the Grignard re-
agent with no CuI added).
Nucleophilic ring opening reactions involving activated
cyclopropanes and amines, mercaptans, malonate anions
or related Michael donors are well known.1 Reaction of
methallyllithium cuprate, which can be generated from
isobutylene with the use of BuLi◊TMEDA complex,2 with
1,1-dimethoxycarbonylcyclopropane provides the ring
opened product3 but requires a large excess of butyllithi-
um which hampers its practical application. Addition of
lithiumcuprate reagents to activated cyclopropanes have
also been studied in detail in the context of certain natural
product syntheses.4,5 However, reaction of cyclopropane
derivatives bearing two geminal alkoxycarbonyl or gemi-
nal alkoxycarbonyl and benzenesulfonyl groups with
Grignard reagents has received little attention. Some time
ago it has been shown that copper chloride-catalyzed ad-
dition of alkyl Grignard reagents to 1,1-dialkoxy-
carbonylcyclopropanes6 and 1,1-diphenyl-sulfonyl-
cyclopropane7 occurs with opening of the cyclopropane
ring. In the course of ongoing studies in one of our labo-
ratories we were interested in applying activated cyclo-
The reaction of the di-iso-propyl ester 1b with the Grig-
nard reagent yielded a mixture of regioisomers 2b and 3b.
The highest proportion of the required product (94:6) was
attained when HMPA (1 mol equiv) was used as a cosol-
vent and the reaction was carried out at -30 °C to -20 °C
for 5 hours and then at room temperature for 15 hours (Ta-
ble, Entry 2). Eventually, pure compound 2b was obtained
in 51% yield after chromatography. The reaction was
slow at temperatures below -40 °C (Table, Entry 3). On
the other hand, at higher temperatures the degree of regio-
selectivity was lower (Table, Entry 4). Replacement of
HMPA with DMPU8 resulted in lowering of the regiose-
lectivity of the reaction (Table, Entry 5).
Scheme 1
Synthesis 2001, No. 1, 145–149 ISSN 0039-7881 © Thieme Stuttgart · New York

146
I. Prowotorow et al.
PAPER
Table Cu-Catalyzed Reaction of Methallyl Grignard Reagent with Cyclopropane Derivatives
Entry Substrate
Cosolvent
Temp. (oC)/Time
Conversion
(%)
Product
Yield (%)
Product
Yield (%)
Ratio 2/3a
1
2
3
4
5
6
7
8
1a
1b
1b
1b
1b
1c
1c
1d
–
-30 to -20, 5 h, then r.t.
-30 to -20, 5 h, then r.t.
-78 to -40, 20 h
100
100
80
100:0
94:6
85
75
–
2a
2b
–
85
51
–
HMPA
HMPA
HMPA
DMPU
HMPA
DMPU
HMPA
87:13
89:11
61:49
89:11
50:50
–
0
100
100
100
100
ca 50
–
–
–
-30 to -20, 5 h, then r.t.
-30 to -20, 5 h, then r.t.
-30 to -20, 5 h, then r.t.
-30 to -20, 5 h, then r.t.
–
–
–
72
–
2c
–
61
–
35
2d
35
a Products ratio determined by GC.
Reactivity of diethyl ester 1c which is one of the cheapest
cyclopropane derivatives, was studied in some detail. A
large scale Cu-catalyzed reaction (0.4 mol) of 1c and
methallylmagnesium chloride in the presence of HMPA
provided the product in 72% yield as a mixture of 2c and
3c in a ratio of 89:11 (Table, Entry 6). Compound 2c was
isolated in pure form by chromatography (61% yield from
1c). However, for synthesis of ester 2h, the mixture of 2c
and 3c could be conveniently used without separation
(vide infra). It is noteworthy that replacement of HMPA
with DMPU resulted in diminishing the regioselectivity of
the addition reaction (Table, Entry 7). The copper mediat-
ed-reaction of methallylmagnesium chloride with phenyl-
sulfonyl derivative 1d was selective with respect to
product 2d (Table, Entry 8) but slower than the reactions
Scheme 2
of the diesters discussed above (a sample of 3d was pre- Dealkoxycarbonylation of diisopropyl esters 2b using the
pared by reaction of 1d and the Grignard reagent with no Krapcho procedure12 followed by distillation afforded the
CuI added). It is noteworthy that the reaction of organo- monoester 2g in 60% yield. Reduction of sulfone 2d with
magnesium reagent with 6,6-dimethyl-5,7-dioxa- sodium amalgam afforded compound 2f in 70% yield. In
spiro[2.5]octane-4,8-dione was impractically slow. The large scale preparation of the mono ester 2h, the crude
observed relative rates of nucleophilic addition to cyclo- mixture of 2c and 3c (89:11 ratio) was subjected to the
propane derivatives 1a-c are likely to reflect the strain of dealkoxycarbonylation reaction and the product was puri-
the cyclopropane ring in these compounds.
fied by distillation (2h was obtained in a 48% yield from
1c).
We failed in all attempts to transform the di-tert-butyl
ester 2a into the corresponding mono-ester or free acid In conclusion, copper-mediated 1,5-(homo)conjugate ad-
under acidic conditions. On treatment of 2a with trifluoro- dition reaction of organomagnesium reagent to 1,1-di-
acetic acid under the conditions typical for tert-butyl ester alkoxycarbonylcyclopopane derivatives was examined
hydrolysis9 a complex mixture of products was formed, with respect to effect of the alkyl groups. Economic meth-
presumably due to participation of the ethylenic bond. On od for the preparation of malonates 2a-d and esters 2e-g
other hand, 2a resisted alkaline hydrolysis under various was developed.
conditions including those applied to very hindered
esters.10 On treatment with methanol and Et3N under high
Melting points were determined on a Kofler hot-stage melting point
pressure11 (12 Kbar) 2a gave the corresponding dimethyl
apparatus. 1H and 13C NMR spectra were taken in CDCl3 on a Vari-
ester 2e (Scheme 2); however the reaction was too slow
an Gemini 200 MHz spectrometer; chemical shifts are given as d
for preparative purposes (60% conversion after 3 days).
Similarly, acid-catalyzed hydrolysis of tert-butyl ester 2f
(prepared as described below) failed to afford the corres-
ponding acid.
values (ppm); DEPT sequence was used for assignments of multi-
plicities in 13C NMR. Mass spectra were determined at an ionizing
voltage of 70 eV. GC analyses were conducted using Shimadzu ap-
paratus, SE 30 column, initial temp. 140 °C with programmed
change of temperature 15 °C/min. Commercial grade magnesium
Synthesis 2001, No. 1, 145–149 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Facile Synthesis of Aliphatic Esters, Malonates and Phenylsulfonyl Esters
147
turnings were used. Air-sensitive reactions were performed in oven-
or flame-dried glassware under argon.
Anal. calcd for C13H22O4 (242.3): C, 64.44; H, 9.15. Found: C,
64.50; H, 9.16.
2-Benzenesulfonyl-6-methylhept-6-enoic Acid tert-Butyl Ester
(2d)
Mp 65 °C (EtOH).
Preparation of a Stock Solution of Methallylmagnesium Chlo-
ride
To a stirred suspension of Mg turnings (100 g, 4.17 gram atom) in
THF (1 L) under argon was added 3-chloro-2-methylpropane (98%,
Fluka, 138.7g, 1.53 mol) dropwise at 0 °C. The solution was stirred
at 0 °C for 3 h and then allowed to warm to r.t. After 1 h, the upper
layer was transferred by a cannula into a reaction vessel or a storage
flask.
IR (film): n = 1724 (C=O), 1648 (C=C), 1142 cm-1.
1H NMR: d = 1.34 (s, 9 H), 1.40-1.54 (m, 2 H), 1.66 (s, 3 H), 1.80-
2.60 (m, 4 H), 3.85 (dd, J = 10.6 Hz, 4.7, 1 H), 4.65 (m, 2 H), 7.50-
7.75 (m, 3 H), 7.85-7.93 (m, 2 H).
13C NMR: d = 22.1, 24.7, 26.3, 27.6, 37.0, 71.2, 83.2, 110.7, 128.8,
129.3, 133.9, 137.4, 144.3, 164.7.
Addition of Methallylmagnesium Chloride to Activated Cyclo-
propanes 1a-e
MS: m/z (%) = 282 ([M+ - 58], 38), 265 (20), 140 (100), 123 (68),
122 (27), 95 (48), 82 (95), 57 (72), 41 (27).
To a solution of methallylmagnesium chloride in THF (1.0 M,
2.0 mL) was added a solution of CuI (74.8 mg) in Me2S (0.6 mL) at
-30 °C followed by HMPA (0.36 mL, 2.0 mmol) and 1,1-diactivat-
ed cyclopropane 1 (1.0 mmol) in THF (0.5 mL). The mixture was
stirred at -30 °C to -20 °C for 5 h, and then set aside at r.t. for
15 h. The reaction was quenched with aq NH4Cl solution (5 mL),
brought to pH 8 with aq 25% NH4OH and the product was extracted
with Et2O (3 î 15 mL). The extract was dried (Na2SO4), the solvent
evaporated and the residue was distilled. Yields and regioisomers
ratios are given in the Table. The regioisomers were separated by
chromatography on a silica gel column. Analytical samples were
purified by distillation in a Kugelrohr apparatus.
MS [LSIMS(+), NBA]: m/z = 699 (14, [2 M + Na+]), 361 (50, [M +
Na+]), 339 (2, [M + H+]).
Anal. calcd for C18H26O4S (338.5): C, 63.88; H, 7.74; S, 9.47.
Found: C, 63.74; H, 7.84; S, 9.60.
1-[1-Hydroxy-3-methyl-1-(2-methylallyl)but-3-enyl]cyclopro-
panecarboxylic Acid tert-Butyl Ester (3a)
A sample of 3a was prepared in the reaction of 1a with methallyl-
Grignard reagent with no CuI added; bp 90-91 °C/0.1 mbar.
IR (film): n = 1713 (C=O), 1642 (C=C) cm-1.
1H NMR: d = 0.98 (4 H, m), 1.42 (s, 9 H), 1.82 (m, 6 H), 2.07 (s, 1
H), 2.45 (d, J = 13.3 Hz, 2 H), 2.78 (d, J = 13.3, 2 H), 4.71 (m, 2 H),
4.88 (m, 2 H).
2-(4-Methylpent-4-enyl)malonic Acid tert-Butyl Ester (2a)
Bp 112-114 °C/0.2 mbar.
IR (film): n = 1746 (C=O), 1729 (C=O), 1649 (C=C) cm-1.
1H NMR: d = 1.45 (s, 18 H), 1.69 (s, 3 H), 1.72-1.88 (m, 4 H), 2.03
(t, J = 7.4 Hz, 2 H), 3.13 (t, J = 7.5 Hz, 1H), 4.54-4.75 (m, 2 H).
13C NMR: d = 12.5, 24.8, 28.04, 30.33, 46.8, 71.2, 80.2, 115.0,
143.4, 173.0.
MS: m/z (%) = 207 (2), 170 (10), 169 (100), 152 (8), 151 (83), 123
(3), 114 (5), 113 (81), 95 (8), 83 (34), 77 (4), 69 (7), 57 (64), 55 (23),
53 (4), 43 (5), 41 (27), 39 (10).
13C NMR: d = 22.2, 25.1, 27.9, 28.1, 37.4, 53.8, 81.2, 110.2, 145.1,
168.9.
MS: m/z (%) = 242 (M+, 0.5), 186 (14), 169 (22), 151 (16), 82 (66),
57 (100).
LSIMS HRMS (electrospray technique): m/z Calcd for
C17H28O3Na: 303.1931. Found: 303.1931.
MS [LSIMS(+), NBA]: m/z = 321 (14, [M + Na+]).
1-[1-Hydroxy-3-methyl-1-(2-methylallyl)but-3-enyl]cyclopro-
panecarboxylic Acid iso-Propyl Ester (3b)
Anal. calcd for C17H30O4 (298.4): C, 68.42; H, 10.13. Found: C,
68.19; H, 10.08.
IR (film): n = 1713 (C=O), 1642 (C=C) cm-1.
1H NMR: d = 1.03 (4 H, m), 1.19 (d, J = 6.3 Hz, 6 H), 1.81 (m, 6 H),
2.08 (s, 1 H), 2.47 (d, J = 13.0 Hz, 2 H), 2.77 (d, J = 13.0, 2 H), 4.73
(m, 2 H), 4.88 (m, 2 H), 4.98 (sept, J = 6.3 Hz, 1 H).
13C NMR: d = 12.5, 21.7, 24.8, 29.9, 46.8, 67.4, 71.2, 115.1, 143.4,
173.3.
2-(4-Methylpent-4-enyl)malonic Acid iso-Propyl Ester (2b)
Bp 155 °C/1.0 mbar (Kugelrohr).
IR (film): n = 1747 (C=O), 1730 (C=O), 1650 (C=C) cm-1.
1H NMR: d = 1.22 (d, J = 6.2 Hz, 12 H), 1.38-1.56 (m, 2 H), 1.69
(s, 3 H), 1.78-1.93 (m, 2 H), 2.03 (t, J = 7.5 Hz, 2 H), 3.25 (t,
J = 7.5 Hz, 1 H), 4.68 (m, 2 H), 5.04 (sept, J = 6.2 Hz, 2 H).
13C NMR: d = 21.6, 21.7, 22.2, 25.2, 28.2, 37.3, 52.3, 68.6, 110.3,
145.0, 169.0.
MS: m/z (%) = 270 (M+, 1), 188 (13),151 (24), 146 (10), 104 (10),
82 (100), 43 (40).
MS: m/z (%) = 211 (27), 169 (60), 114 (6), 113 (100), 95 (9), 83
(34), 69 (8), 55 (23), 43 (15), 41 (14), 39 (6).
MS [LSIMS(+), NBA]: m/z = 267 ([M + H+]).
HRMS: m/z Calcd for (M + H+) C16H27O3: 267.1960. Found:
267.1957.
1-[1-Hydroxy-3-methyl-1-(2-methylallyl)but-3-enyl]cyclopro-
panecarboxylic Acid Ethyl Ester (3c)
Bp 82-84 °C/0.1 mbar.
IR (film): n = 1718 (C=O), 1642 (C=C) cm-1.
1H NMR: d = 1.05 (m, 4 H), 1.21 (t, J = 7.1 Hz, 3 H), 1.81 (m, 6 H),
2.06 (s, 1 H), 2.47 (d, J = 13.3 Hz, 2 H), 2.77 (d, J = 13.3 Hz, 2 H),
4.07 (q, J = 7.1 Hz, 2 H), 4.70 (m, 2 H), 4.87 (m, 2 H).
HRMS: m/z Calcd for C15H26O4: 270.1831. Found: 270.1805.
2-(4-Methylpent-4-enyl)malonic Acid Ethyl Ester (2c)
Bp 150 °C/1.0 mbar (Kugelrohr).
IR (film): n = 1734 (C=O), 1752 (C=O), 1649 (C=C) cm-1.
1H NMR: d = 1.25 (t, J = 7.1 Hz, 6H), 1.35-1.55 (m, 2 H), 1.68 (s,
3 H), 1.80-1.93 (m, 2 H), 2.02 (t, J = 7.5 Hz, 2 H), 3.30 (t, J = 7.5
Hz, 1 H), 4.15 (q, J = 7.1 Hz, 4 H), 4.70 (m, 2 H).
13C NMR: d = 14.17, 22.2, 25.1, 28.2, 37.2, 51.9, 61.19, 110.3,
144.8, 169.3.
MS: m/z (%) = 242 (M+, 1), 197 (26), 173 (43), 160 (100), 151 (65),
82 (57).
13C NMR: d = 12.5, 14.16, 24.7, 29.8, 46.8, 60.1, 71.2, 115.1, 143.3,
173.8.
MS: m/z (%) = 207 (2), 198 (8), 197 (67), 152 (5), 151 (48), 141
(100), 123 (4), 113 (29), 95 (5), 83 (27), 69 (8), 55 (18), 53 (3), 43
(2), 41 (8), 39 (6).
MS [LSIMS(+), NBA]: m/z = 243 (39, [M + H+]).
Synthesis 2001, No. 1, 145–149 ISSN 0039-7881 © Thieme Stuttgart · New York

148
I. Prowotorow et al.
PAPER
LSIMS HRMS (electrospray technique): m/z Calcd for
6-Methyl-6-heptenoic Acid iso-Propyl Ester (2g)
Yield: 60%; bp 140 °C/80 mbar (Kugelrohr).
(C15H24O3Na)+: 275.1618. Found: 275.1599.
4-(1-Benzenesulfonylcyclopropyl)-2,6-dimethylhepta-1,6-di-
en-4-ol (3d)
Mp 86 °C.
IR (film): n = 1140, 1285, 1640, 3480 cm-1.
IR (film): n = 1732 (C=O), 1650 (C=C) cm-1.
1H NMR: d = 1.18 (d, J = 6.3, 6 H), 1.36-1.65 (m, 4 H), 1.66 (s,
3 H), 1.98 (t, J = 7.1 Hz, 2 H), 2.24 (t, J = 7.5 Hz, 2 H), 4.64 (m,
2 H), 4.96 (sept, J = 6.3 Hz, 1 H).
1H NMR: d = 1.30 (m, 4 H), 1.82 (s, 6 H), 2.38 (s, 1 H), 2.44 (d,
J = 13.5 Hz, 2 H), 2.64 (d, J = 13.5, 2 H), 4.71 (m, 2 H), 4.94 (m,
2 H), 7.58 (m, 3 H), 7.92 (m, 2 H).
13C NMR: d = 10.5, 25.1, 29.7, 45.9, 71.5, 116.2, 128.9, 129.1,
133.4, 140.9, 142.6.
13C NMR: d = 21.8, 22.2, 24.6, 26.9, 34.4, 37.3, 67.2, 109.9, 145.3,
173.1.
MS: m/z (%) = 184 (M+, 2), 141 (10), 125 (22), 124 (17), 97 (15),
95 (11), 87 (10), 83 (18), 82 (100), 69 (19), 67 (13), 56 (19), 55 (30),
43 (23), 41 (27), 39 (12).
MS: m/z (%) = 265 (22), 210 (11), 209 (100), 141 (9), 117 (8), 105
HRMS: m/z Calcd for C11H20O2: 184.1463. Found: 184.1467.
(39), 77 (16).
Ethyl 6-Methylhept-6-enoate (2h)
Yield: 67%; bp 80-82 °C/5.0 mbar.
IR (film): n = 1737 (C=O), 1650 (C=C) cm-1.
1H NMR: d = 1.23 (t, J = 7.2 Hz, 3 H), 1.36-1.65 (m, 4 H), 1.69 (s,
3 H), 2.01 (t, J = 7.0 Hz, 2 H), 2.29 (t, J = 7.2 Hz, 2 H), 4.10 (q,
J = 7.2 Hz, 2 H), 4.67 (m, 2 H).
13C NMR: d = 14.2, 22.2, 24.5, 27.0, 34.2, 37.3, 60.12.2, 110.0,
145.4, 173.7;
MS: m/z (%) = 170 (M+, 11), 124 (20), 82 (100), 55 (34), 41 (26).
MS [LSIMS(+), NBA]: m/z = 343 (30, [M + Na+]), 321 (2, [M +
H+]).
HRMS: m/z Calcd for (M + Na+) C18H24O3NaS: 343.1344. Found:
343.1364.
2-(4-Methylpent-4-enyl)malonic Acid Methyl Ester (2e)
A solution of 2a (0.238 g, 0.78 mmol) in MeOH (4.0 mL) contain-
ing Et3N (0.55 mL, 3.9 mmol) was kept under pressure 12 kbar for
3 d. The solvent was evaporated and the residue was chromato-
graphed on silica gel (10 g, hexane/EtOAc, 20:1) to give 2e
(0.975 g, 65%); bp 150 °C/4.0 mbar (Kugelrohr).
HRMS: m/z Calcd for C10H18O2: 170.1307. Found: 170.1288.
IR (film): n = 1737 (C=O), 1754 (C=O), 1649 (C=C) cm-1.
1H NMR: d = 1.35-1.51 (m, 2 H), 1.68 (s, 3 H), 1.80-1.95 (m, 2 H),
2.02 (t, J = 7.5 Hz, 2 H), 3.36 (t, J = 7.8 Hz, 1 H), 3.72 (s, 6 H), 4.67
(m, 2 H).
Ethyl 6-Methylhept-6-enoate 2h from 1c
To a solution of methallylmagnesium chloride in THF (prepared as
above, 1 L) cooled to -30 °C was added a solution of CuI (30.0 g,
0.16 mol) in Me2S (250 mL). The mixture was stirred at - 30 °C for
30 min and then HMPA (125 mL, 0.70 mol) was added followed by
1,1-diethoxycarbonylcyclopropane (1c; 73.0 g, 0.39 mol). The mix-
ture was maintained at -30 °C to -20 °C for 5 h and then it was set
aside at r.t. for 15 h. Sat. aq of NH4Cl brought to pH 8 with 25% aq
ammonia (500 mL) carefully added. The layers were separated and
the aqueous layer was extracted with Et2O (3 î 300 mL). Combined
organic solutions were washed with aq sat. NH4Cl and brine, and
dried. The solvent was evaporated and the residue was distilled
from an oil bath collecting the fraction at 130-135 °C/1 mbar (bath
temp. 170 °C). Product consisting of a mixture 2c and 3c (67.0 g,
2c/3c = 89:11 by GC, 72% total yield) was obtained. A sample of
this mixture (1 g) was chromatographed on a silica gel column (100
g, hexane/EtOAc, 9:1) to give 2c (0.85 g, 61%). A mixture 2c and
3c (50.0 g, 0.21 mol), prepared as described above, was dissolved
in DMSO (330 mL). LiCl (25.5 g, 0.60 mol) and H2O (3.7 mL, 0.2
mol) were added and the mixture was heated at 175-178 °C for 6 h.
After cooling, the mixture was poured into H2O and ice (400 mL)
and the product was extracted with Et2O (3 î 250 mL). Combined
organic extracts were dried and the solvent was evaporated. The res-
idue was distilled collecting the fraction at 80 °C/5 mbar (bath
temp. 115 °C); yield: 23.8 g (67%); 99.5% pure by GC.
13C NMR: d = 22.1, 25.1, 28.3, 37.2, 51.5, 52.4, 110.4, 114.8, 169.8.
MS: m/z (%) = 151 (68), 82 (100).
MS [LSIMS(+), NBA9: m/z = 215 (8, [M + H+]), 214 (6).
HRMS: m/z Calcd for C11H18O4: 214.1205. Found: 214.1205.
6-Methyl-6-heptenoic Acid tert-Butyl Ester (2f)
To a solution of sulfone 2d (220 mg, 0.65 mmol) in MeOH (6.5 mL)
were added Na2HPO4 (0.369 g, 2.6 mmol) and 5% sodium amalgam
(0.975 g) at 0 °C. The mixture was stirred at r.t. for 1 h and then
poured into H2O. The product was extracted with Et2O (3 î 15 mL).
The extract was evaporated and the residue was chromatographed
on silica gel (6 g, hexane/EtOAc, 9:1); yield: 89.0 mg (70%); bp
110 °C/5.0 mbar (Kugelrohr).
IR (film): n = 1732 (C=O), 1650 (C=C) cm-1.
1H NMR: d = 1.48 (s, 9 H), 1.40-1.70 (m, 4 H), 1.73 (s, 3 H), 2.05
(t, J = 7.4 Hz, 2 H), 2.26 (t, J = 7.4 Hz, 2 H), 4.67 (m, 2 H).
13C NMR: d = 22.4, 24.8, 27.0, 28.1, 35.5, 37.5, 79.9, 109.9, 145.5,
173.0.
MS: m/z (%) = 142 ([M - 56]+, (28), 125 (32), 124 (22), 97 (13), 82
(56), 57 (100), 55 (22), 41 (22), 39 (7).
HRMS: m/z Calcd for (M - 56)+ C8H14O2: 142.0994. Found:
142.0986.
2-Methylethyl 6-Methylhept-6-enoate (2g)
Conjugate addition reaction was carried out in an analogous manner
as that described above using Mg (5 g), methallyl chloride (6.2 g,
0.68 mol), THF (45 mL), CuI (1.0 g, 5.25 mmol), Me2S (8 mL) and
1b (3.3 g, 0.016 mol). The product was distilled collecting the frac-
tion at 140-145 °C/1 mbar (bath temp. 170 °C). A mixture of 2b
and 3b was obtained (3.0 g) in 70% yield in a ratio of 93:7 as deter-
mined by GC. Compound 2b (0.137 g, 51%) colud be separated by
chromatography of a sample of the mixture (0.208 g) on a silica gel
column (25 g) using hexane/EtOAc (9:1) as eluent. A mixture of 2b
and 3b (2.4 g), LiCl (1.65 g), H2O (0.27 g) and DMSO (15 mL) was
heated at 180 °C for 12 h. The product was isolated in an analogous
way as in the experiment described above. Distillation at 140 °C/80
mbar gave ester 2g (0.92 g, 60%, 95% pure by GC).
Dealkoxycarbonylation of 2b,c; General Procedure12
To a solution of LiCl (1.1 g, 24.9 mmol) in DMSO (14.0 mL) were
added H2O (0.15 mL, 8.3 mmol) and the respective malonate
(8.3 mmol). The mixture was heated at 150-180 °C for 10 h to
12 h. Then the product and DMSO was distilled off (the fractions
distilling below 180 °C were collected). The distillate was diluted
with H2O (15 mL), the organic layer separated and the aqueous lay-
er was extracted with Et2O (3 î 15 mL). The combined organic ex-
tracts were washed with H2O (3 î 20 mL) and the solvent was
evaporated. The residue was distilled in a Kugelrohr apparatus.
Synthesis 2001, No. 1, 145–149 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Facile Synthesis of Aliphatic Esters, Malonates and Phenylsulfonyl Esters
149
(7) Trost, B. M.; Cossy, J.; Burks, J. J. Am. Chem. Soc. 1983, 105,
1052.
(8) Mukhopahyay, T.; Seebach, D. Helv. Chim. Acta 1982, 65,
385.
Acknowledgement
We thank Dr. Piotr Sa¥aÆski of the Institute of Organic Chemistry,
Warsaw, for conducting high pressure experiments.
(9) Bryan, D. B.; Hall, R. F.; Holden, K. G.; Huffman, W. F.;
Gleason, J. G. J. Am. Chem. Soc. 1977, 99, 2353.
(10) Hasegawa, T.; Yamamoto, H. Synlett 1998, 882.
(11) Yamamoto, Y.; Furuta, T.; Matsuo, J.; Kurata, T. J. Org.
Chem. 1991, 56, 5737.
References
(1) Danishefsky, S. Acc. Chem. Res. 1979, 12, 66.
(2) Akiyama, S.; Hooz, J. Tetrahedron Lett. 1973, 4115.
(3) Daviaud, G.; Miginiac, P. Tetrahedron Lett. 1972, 997.
(4) Trost, B. M.; Taber, D. F.; Alper, J. B. Tetrahedron Lett. 1976,
3857.
(5) Newton, R. F.; Roberts, S. M. Tetrahedron 1980, 36, 2163.
(6) Nielsen, B. H.; Munch-Petersen, J. J. Organometal. Chem.
1964, 2, 493.
(12) Krapcho, A. P. Synthesis 1982, 805.
Article Identifier:
1437-210X,E;2001,0,01,0145,0149,ftx,en;P05000SS.pdf
Synthesis 2001, No. 1, 145–149 ISSN 0039-7881 © Thieme Stuttgart · New York