General method for the synthesis of phenyliodonium ylides from malonate esters: Easy access to 1,1-cyclopropane diesters

Article abstract of DOI:10.1021/jo802208q

(Chemical Equation Presented) A general method to access phenyliodonium ylides from malonates has been developed. These ylides provide easy access to a variety of useful 1,1-cyclopropane diesters using rhodium or copper catalysis. Moreover, the iodonium ylide of dimethyl malonate was obtained in 78% yield using improved conditions that involve a simple filtration step to isolate the desired product. This ylide was shown to be a safer and convenient alternative to the corresponding diazo compound and a very efficient way to 1,1-cyclopropane diesters when used with a catalytic amount of Rh₂(esp)₂.

Full text of DOI:10.1021/jo802208q

S. R. Goudreau, D. Marcoux and A. B. Charette
S1
SUPPORTING INFORMATION
General Method for the Synthesis of Phenyliodonium Ylides from
Malonate Esters: Easy Access to 1,1-Cyclopropane Diesters
Sébastien R. Goudreau, David Marcoux and André B. Charette*
Département de Chimie, Université de Montréal, P.O. Box 6128, Station Downtown, Québec,
Canada H3C 3J7. E-Mail: andre.charette@umontreal.ca
Table of content .............................................................................................................................S1
Experimental procedures and characterization data for new compounds......................................S2
Compound 1f.......................................................................................................................S2
Compound 1a-g...................................................................................................................S3
Compound 2a-f....................................................................................................................S4
Compound 3a-g...................................................................................................................S6
1
13
H and C NMR spectra................................................................................................................S9
DSC analyses ..............................................................................................................................S48

S. R. Goudreau, D. Marcoux and A. B. Charette
S2
General: All non-aqueous reactions were run under an inert atmosphere (nitrogen or argon)
1
using standard techniques for manipulating air-sensitive compounds. Anhydrous solvents were
2 2 3
obtained either by filtration through drying columns (THF, ether, CH Cl , benzene, DMF, CH CN,
toluene, hexane, methanol). Analytical thin-layer chromatography (TLC) was performed on
precoated, glass-backed silica gel. Visualization of the developed chromatogram was performed by
UV absorbance, aqueous cerium molybdate, or aqueous potassium permanganate. Flash column
chromatography was performed using 230-400 mesh silica of the indicated solvent system
2
according to standard technique. Melting points were obtained on a melting point apparatus and
are uncorrected. Infrared spectra were taken on a FTIR apparatus and are reported in reciprocal
-
1
1
13
centimeters (cm ). Nuclear magnetic resonance spectra ( H, C, DEPT 135, COSY, HMQC,
1
NOESY) were recorded either on a 300 or 400 MHz spectrometer. Chemical shifts for H NMR
spectra are recorded in parts per million from tetramethylsilane with the solvent resonance as the
internal standard (chloroform, δ 7.27 ppm). Data are reported as follows: chemical shift, multiplicity
(
s = singlet, d = doublet, t = triplet, q = quartet, qn = quintet, m = multiplet and br = broad), coupling
13
constant in Hz, integration. Chemical shifts for C NMR spectra are recorded in parts per million
from tetramethylsilane using the central peak of deuterochloroform (77.00 ppm) as the internal
standard. All spectra were obtained with complete proton decoupling. When ambiguous, proton
and carbon assignments were established using COSY, HMQC and DEPT experiments.
Reagents: Unless otherwise stated, commercial reagents were used without purification.
PhI(OAc) , malonate esters, alkenes, Rh (OAc) , Rh (esp) , (CuOTf) •C H were commercially
2 2 4 2 2 2 6 6
available. PhI=O was synthesized according to a previously reported procedure. Diazomethyl
3
malonate (1h) and diazodiisopropyl malonate (1i) were synthesized according to a previously
4
reported procedure.
O
O
MeO
OMe
IPh
1
f
Synthesis of Bis(methoxycarbonyl)(phenyliodinio)methanide (1f)
In a 50-mL flask under argon were added KOH (2.00 g, 36.0 mmol), MeCN (20 mL) and dimethyl
malonate (693 μL, 6.00 mmol). The heterogeneous mixture was cooled at 0 °C (ice/water bath) and
was stirred vigorously for 5 min to produce a milky white suspension. PhI(OAc)
mmol) was then added in one portion and the reaction mixture was stirred vigorously for 2.0 h at 0
C. The reaction mixture gradually became a thick creamy mixture. Water (10 mL) was then added
2
(2.13 g, 6.60
°
and the mixture was stirred for 1 min. The beige/yellow biphasic solution containing a fluffy white
suspension was filtered. The solid was washed with water (2 x 5 mL). It is important that the
solvent be completely removed between each wash. The solid was finally washed with Et
2
O (10
mL) then dried under high vacuum to yield 1f as an off-white solid (1.56 g, 78%): mp 100 °C
1
(
2
(
decomposition); H NMR (300 MHz, CDCl ) δ 7.77-7.72 (m, 2H), 7.56-7.50 (m, 1H), 7.44-7.37 (m,
3
13
H), 3.74 (s, 6H); C NMR (75 MHz, CDCl ) δ 166.3 (2), 131.6 (2), 131.5 (2), 131.3, 114.3, 52.4
3
-1
2); IR (neat) 3081, 2982, 2948, 2899, 1668, 1585, 1575, 1562, 1435, 1425, 1320, 1060, 990 cm ;
Anal. calcd for C11 : C, 39.54; H, 3.35; found: C, 39.05; H, 3.34. The spectral data were
H11IO
4
5
consistent with that previously reported. The product partially degraded during the preparation of
the NMR sample.
1
Shriver, D. F.; Drezdzon, M. A. The manipulation of air-sensitive compounds; 2nd Edition ed.; Wiley: New York, 1986.
Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.
Saltzman, H.; Sharefkin, J. G. Org. Synth. 1973, 5, 658; 1963, 43, 60.
Tallis, J. S.; Helquist, P. Org. Synth. 1998, 74, 229.
2
3
4
5
Müller, P.; Fernández, D. Helv. Chim. Acta 1995, 78, 947.

S. R. Goudreau, D. Marcoux and A. B. Charette
S3
General procedure for the synthesis of iodonium ylides:
In a 100 mL flask under argon were added KOH (2.00 g, 36.0 mmol), CH
Cl
2 2
(20 mL) and the
malonate (7.20 mmol). The heterogeneous mixture was put in a room temperature water bath (20
C) and was stirred vigorously for 5 min to produce a milky white suspension. PhI(OAc) (1.93 g,
.00 mmol) was then added in one portion and the reaction mixture was stirred vigorously for 2.0 h
at room temperature. The reaction mixture gradually became yellow. The heterogeneous mixture
was then filtered on a cotton plug and the flask was washed five times with CH Cl (5 mL). The
°
2
6
2
2
yellow solution was then concentrated under reduced pressure at room temperature (20 °C) and
then put under high vacuum for 1 h.
O
O
i-PrO
Oi-Pr
IPh
1
a
Bis(isopropoxycarbonyl)(phenyliodinio)methanide (1a). Purification: dissolved in a minimum of
CH Cl , crystallized by adding hexane, filtered on Büchner and washed with hexane to yield 1.78 g
76% yield) of a white solid: mp 105 °C (decomposition); H NMR (300 MHz, CDCl ) δ 7.76-7.71
2
2
1
(
3
(
1
m, 2H), 7.53-7.47 (m, 1H), 7.41-7.34 (m, 2H), 4.99 (septet, J = 6.2 Hz, 2H), 1.22 (d, J = 6.2 Hz,
13
2H); C NMR (75 MHz, CDCl ) δ 165.3 (2), 131.6 (2), 131.0 (2), 130.2, 114.6, 67.7 (2), 22.3 (4);
3
-
1
IR (neat) 3043, 2979, 2936, 1599, 1568, 1366, 1301, 1054, 1000, 992 cm ; Anal. calcd for
: C, 46.17; H, 4.91; found: C, 46.16; H, 4.81. The product partially degraded during the
preparation of the NMR sample.
15 4
C H19IO
O
O
EtO
OEt
IPh
1
b
Bis(ethoxycarbonyl)(phenyliodinio)methanide (1b). Purification: dissolved in a minimum of
CH Cl , crystallized by adding hexane, filtered on Büchner and washed with hexane to yield 826
mg (38% yield) of a white solid: mp 72 °C (decomposition); H NMR (300 MHz, CDCl ) δ 7.75-7.70
2
2
1
3
13
(
m, 2H), 7.53-7.47 (m, 1H), 7.41-7.34 (m, 2H), 4.16 (q, J = 7.1 Hz, 4H), 1.25 (t, J = 7.1 Hz, 6H); C
NMR (75 MHz, CDCl ) δ 165.9 (2), 131.6 (2), 131.4 (2), 131.2, 114.4, 60.8 (2), 14.7 (2); IR (neat)
3
-
1
3
581, 3515, 3042, 2980, 1600, 1566, 1364, 1321, 1295, 1223, 1163, 1069, 1038, 991 cm ; Anal.
calcd for C13 : C, 43.11; H, 4.17; found: C, 42.68; H, 4.24. The product partially degraded
during the preparation of the NMR sample.
H15IO
4
O
O
t-BuO
Ot-Bu
IPh
1c
Bis(tert-butoxycarbonyl)(phenyliodinio)methanide (1c). Purification: triturated in hexane,
filtered on Büchner and washed with hexane to yield 1.88 g (75% yield) of a beige solid: mp 94 °C
1
(
decomposition); H NMR (300 MHz, CDCl ) δ 7.65-7.60 (m, 2H), 7.43-7.37 (m, 1H), 7.33-7.26 (m,
3
13
2
H), 1.36 (s, 18H); C NMR (75 MHz, CDCl ) δ 165.1 (2), 131.0 (2), 130.7 (2), 130.6, 114.5, 79.5
3
-
1
(
2), 28.5 (6); IR (neat) 2982, 2937, 1750, 1738, 1368, 1272, 1255, 1146 cm ; Anal. calcd for
: C, 48.82; H, 5.54; found: C, 49.21; H, 5.63. The product partially degraded during the
preparation of the NMR sample.
17 4
C H23IO

S. R. Goudreau, D. Marcoux and A. B. Charette
S4
O
O
BnO
OBn
IPh
1d
Bis(benzoxy)(phenyliodinio)methanide (1d). Unable to isolate this ylide analytically pure.
Trimethoxybenzene was added as internal standard before concentration to determine the yield
(
determined from the pic at 3.78 ppm (trimethoxybenzene) and the pic at 5.21 ppm (1d)). Crude
1
brown oil (53% yield) was obtained: H NMR (400 MHz, CDCl ) δ 7.68-7.64 (m, 2H), 7.53-7.49 (m,
3
1
H), 7.40-7.21 (m, 12H), 5.21 (s, 4H).
O
O
EtO
Ot-Bu
IPh
1e
(
tert-Butoxycarbonyl)(ethoxycarbonyl)(phenyliodinio)methanide (1e). Purification: triturated in
hexane, filtered on Büchner and washed with hexane to yield 1.71 g (73% yield) of a beige solid:
1
mp 105 °C (decomposition); H NMR (400 MHz, CDCl ) δ 7.71-7.65 (m, 2H), 7.47-7.42 (m, 1H),
3
13
7
.36-7.31 (m, 2H), 4.12 (q, J = 7.1 Hz, 2H), 1.40 (s, 9H), 1.21 (t, J = 7.1 Hz, 3H); C NMR (100
MHz, CDCl ) δ 166.2, 164.8, 131.2 (2), 131.1 (2), 130.8, 114.5, 79.7, 60.6, 28.4 (3), 14.6; IR (neat)
3
-
1
3
058, 2991, 2971, 2927, 1618, 1325, 1215, 1162, 1059, 1045, 1011, 989 cm ; Anal. calcd for
: C, 46.17; H, 4.91; found: C, 46.39; H, 4.86. The product partially degraded during the
preparation of the NMR sample.
15 4
C H19IO
O
O
O
O
IPh
1
g
2
-Phenyliodonio-5,5-dimethyl-4,6-dioxa-1,3-dioxocyclohexane methylide (1g). Purification:
triturated in hexane, filtered on Büchner and washed with hexane to yield 1.46 g (70% yield) of a
6
1
white solid: mp 92 °C (decomposition), [lit. 97 °C (decomposition)]; H NMR (300 MHz, CDCl ) δ
3
13
7
1
1
3
.92-7.86 (m, 2H), 7.60-7.54 (m, 1H), 7.46-7.38 (m, 2H), 1.70 (s, 6H); C NMR (75 MHz, CDCl ) δ
3
63.7 (2), 132.9 (2), 131.5, 131.4 (2), 114.6, 104.3, 56.1, 25.6 (2); IR (neat) 2982, 2844, 1622,
283, 1192, 1026, 991, 908 cm ; HRMS (ESI) calcd for C12
46.9775. The spectral data were consistent with that previously reported.
-
1
+
H
11IO
4
[M+H] : 346.9778, found
7
General procedure for the cyclopropanation of styrene with iodonium ylides or
diazomalonates catalyzed by rhodium or copper: Cyclopropanes 2a-f were prepared according
to the following general procedure. In a 10 mL flask was added styrene (573 µL, 5.00 mmol),
2 2
CH Cl (2.0 mL) and the catalyst (5.0 µmol, 0.5 mol %). The iodonium ylide or the diazomalonate
(
1.00 mmol) was then added in one portion (iodonium ylide) or over 1 h (diazomalonate) at room
temperature. Reaction mixture was stirred for 3 h. The solution was then concentrated and purified
by flash chromatography on silica gel.
6
Schank, K.; Lick, C. Synthesis 1983, 392.
Müller, P.; Allenbach, Y.; Robert, E. Tetrahedron: Asymmetry 2003, 14, 779.
7

S. R. Goudreau, D. Marcoux and A. B. Charette
S5
H
CO i-Pr
2
Ph
CO i-Pr
2
2
a
Diisopropyl 2-phenylcyclopropane-1,1-dicarboxylate (2a). Iodonium ylide 1a and (CuOTf)•C
6 6
H
was used. Purified by chromatography on silica gel (5% EtOAc/hexane) to yield 177 mg (61%
1
yield) of colorless oil: R 0.38 (10% EtOAc/hexane); H NMR (400 MHz, CDCl ) δ 7.28-7.17 (m,
f
3
5
H), 5.09 (septet, J = 6.3 Hz, 1H), 4.72 (septet, J = 6.3 Hz, 1H), 2.13 (dd, J = 8.0, 5.2 Hz, 1H), 1.64
(
dd, J = 9.2, 5.2 Hz, 1H), 1.28 (d, J = 6.3 Hz, 3H), 1.26 (d, J = 6.3 Hz, 3H), 1.05 (d, J = 6.3 Hz, 3H),
13
0
1
1
.68 (d, J = 6.3 Hz, 3H); C NMR (100 MHz, CDCl ) δ 169.5, 166.2, 134.7, 128.5 (2), 128.0 (2),
3
27.1, 69.2, 68.5, 37.8, 31.7, 21.7, 21.6, 21.2, 21.0, 18.3; IR (neat) 2980, 2937, 1717, 1374, 1315,
-
1
+
22 4
275, 1215, 1099 cm ; HRMS (ESI) calcd for C17H O [M+Na] : 313.1410, found 313.1413.
H
CO Et
2
Ph
CO Et
2
2b
Diethyl 2-phenylcyclopropane-1,1-dicarboxylate (2b). Iodonium ylide 1b (0.85 mmol) and
Rh (OAc) was used. Purified by chromatography on silica gel (5% EtOAc/hexane) to yield 108 mg
49% yield) of colorless oil: R 0.34 (10% EtOAc/hexane); H NMR (400 MHz, CDCl ) δ 7.29-7.19
2
4
1
(
(
5
f
3
m, 5H), 4.32-4.18 (m, 2H), 3.85 (qd, J = 7.2, 0.4 Hz, 2H), 3.22 (t, J = 8.6 Hz, 1H), 2.18 (dd, J = 8.0,
.2 Hz, 1H), 1.71 (dd, J = 9.2, 5.2 Hz, 1H), 1.30 (t, J = 7.2 Hz, 3H), 0.86 (t, J = 7.2 Hz, 3H); C
13
NMR (100 MHz, CDCl ) δ 169.9, 166.6, 134.6, 128.5 (2), 128.1 (2), 127.3, 61.7, 61.1, 37.4, 32.1,
3
-
1
1
8.7, 14.1, 13.6; IR (neat) 2982, 1720, 1321, 1273, 1213, 1188, 1129 cm . The spectral data were
consistent with that previously reported.
8
H
CO t-Bu
2
Ph
CO t-Bu
2
2
c
Di-tert-butyl 2-phenylcyclopropane-1,1-dicarboxylate (2c). Iodonium ylide 1c and Rh
2 4
(OAc)
was used. Purified by chromatography on silica gel (5% EtOAc/hexane) to yield 74.7 mg (47%
1
yield) of a white solid: mp 101-103 °C; R 0.47 (10% EtOAc/hexane); H NMR (400 MHz, CDCl ) δ
f
3
7
1
.29-7.18 (m, 5H), 3.10 (t, J = 8.6 Hz, 1H), 2.03 (dd, J = 7.8, 5.0 Hz, 1H), 1.53 (dd, J = 9.0, 5.0 Hz,
13
H), 1.51 (s, 9H), 1.10 (s, 9H); C NMR (100 MHz, CDCl ) δ 169.2, 165.8, 134.9, 128.7 (2), 127.9
3
(
2), 126.9, 81.6, 80.8, 39.2, 30.8, 28.0 (3), 27.4 (3), 17.6; IR (neat) 2977, 2932, 1715, 1367, 1333,
-
1
9
1
289, 1165, 1126 cm . The spectral data were consistent with that previously reported.
H
CO Bn
2
Ph
CO Bn
2
2d
Dibenzyl 2-phenylcyclopropane-1,1-dicarboxylate (2d). Iodonium ylide 1d (crude mixture) and
CuOTf)•C was used. Purified by chromatography on silica gel (10% EtOAc/hexane) to yield 97
mg (25% yield, 2 steps) of a white solid: mp 67-69 °C (lit. 67-69 °C); R 0.30 (10% EtOAc/hexane);
(
6 6
H
8
f
1
H NMR (400 MHz, CDCl ) δ 7.37-7.18 (m, 13H), 6.97-6.92 (m, 2H), 5.28 (d, J = 12.4 Hz, 1H), 5.17
3
(
d, J = 12.4 Hz, 1H), 4.76 (s, 2H), 3.29 (t, J = 8.6 Hz, 1H), 2.24 (dd, J = 8.1, 5.2 Hz, 1H), 1.78 (dd, J
13
=
1
1
9.2, 5.2 Hz, 1H); C NMR (100 MHz, CDCl ) δ 169.5, 166.3, 135.3, 135.0, 134.3, 128.4, 128.2,
3
28.1, 128.0, 127.9, 127.8, 127.3, 67.2, 67.1, 37.4, 32.6, 19.1; IR (neat) 3032, 2952, 1721, 1320,
-
1
8
270, 1212, 1178, 1125 cm . The spectral data were consistent with that previously reported.
8
Watanabe, S.; Nakayama, I.; Kataoka, T. Eur. J. Org. Chem. 2005, 1493.
Doyle, M. P.; Hu, W. ARKIVOC 2003, 7, 15.
9

S. R. Goudreau, D. Marcoux and A. B. Charette
S6
H
CO t-Bu
2
Ph
CO Et
2
2
e
1
-tert-Butyl 1-ethyl (1S*,2R*)-2-phenylcyclopropane-1,1-dicarboxylate (2e). Purified by
chromatography on silica gel (5% EtOAc/hexane) to yield 58.0 mg (40% yield) of colorless oil: R
f
1
0
3
0
1
1
.43 (10% EtOAc/hexane); H NMR (300 MHz, CDCl ) δ 7.31-7.18 (m, 5H), 3.94-3.77 (m, 2H),
3
.15 (t, J = 8.6 Hz, 1H), 2.11 (dd, J = 7.9, 5.1 Hz, 1H), 1.64 (dd, J = 9.2, 5.1 Hz, 1H), 1.51 (s, 9H),
13
.91 (t, J = 7.2 Hz, 3H); C NMR (75 MHz, CDCl ) δ 168.7, 166.9, 134.9, 128.4 (2), 128.0 (2),
3
27.0, 81.9, 60.8, 38.4, 31.3, 27.9 (3), 18.2, 13.7; IR (neat) 2979, 2934, 1716, 1368, 1288, 1165,
-
1
+
22 4
126 cm ; HRMS (ESI) calcd for C17H O [M+Na] : 313.1410, found 313.1411.
General procedure for the synthesis of 1,1-cyclopropanediesters using Rh
Cyclopropanes 2f, 3a-g were prepared according to the following general procedure. In a 25 mL
flask under argon were added Rh (esp) (2.0 mg, 2.5 µmol), CH Cl (5.0 mL) and the alkene (2.50
mmol). The reaction mixture was cooled at 0 °C (ice/water bath) and the iodonium ylide 1f (1.09 g,
.25 mmol) was added in one portion (or in small portions if it reacts too quickly). Reaction mixture
2 2
(esp) :
2
2
2
2
3
was stirred for 15 min at 0 °C and then 2 h at room temperature. The solution was then
concentrated and purified by chromatography on silica gel.
H
CO Me
2
Ph
CO Me
2
2f
2 2
Dimethyl 2-phenylcyclopropane-1,1-dicarboxylate (2f). 0.005 mol % of Rh (esp) was used and
the reaction was performed on a 5 mmol scale. Purified by chromatography on silica gel (10%
1
EtOAc/hexane) to yield 1.07 g (91% yield) of a colorless oil: R 0.53 (20% EtOAc/hexane); H NMR
f
(
400 MHz, CDCl ) δ 7.28-7.17 (m, 5H), 3.77 (s, 3H), 3.34 (s, 3H), 3.23 (t, J = 8.6 Hz, 1H), 2.19 (dd,
3
13
J = 8.0, 5.2 Hz, 1H), 1.73 (dd, J = 9.2, 5.2 Hz, 1H); C NMR (100 MHz, CDCl ) δ 170.1, 166.9,
3
1
1
34.5, 128.3 (2), 128.0 (2), 127.3, 52.6, 52.0, 37.1, 32.4, 19.0; IR (neat) 2953, 1726, 1436, 1332,
277, 1 217, 1130 cm . The spectral data were consistent with that previously reported.
-
1
1
0
H
CO Me
2
CO Me
2
MeO
3a
Dimethyl
2-(4-methoxyphenyl)cyclopropane-1,1-dicarboxylate
(3a).
Purified
by
chromatography on silica gel (10% EtOAc/hexane) to yield 515 mg (78% yield) of a colorless oil: R
f
1
0
3
.41 (20% EtOAc/hexane); H NMR (400 MHz, CDCl ) δ 7.12-7.09 (m, 2H), 6.81-6.77 (m, 2H),
3
.77 (s, 3H), 3.76 (s, 3H), 3.38 (s, 3H), 3.17 (t, J = 8.8 Hz, 1H), 2.14 (dd, J = 8.0, 5.2 Hz, 1H), 1.71
13
(
dd, J = 9.2, 5.2 Hz, 1H); C NMR (100 MHz, CDCl ) δ 170.2, 167.1, 158.8, 129.5 (2), 126.3,
3
1
1
13.5 (2), 55.1, 52.7, 52.2, 37.0, 32.1, 19.2; IR (neat) 3002, 2953, 2838, 1721, 1612, 1516, 1435,
-1
276, 1247, 1216, 1174, 1128 cm . The spectral data were consistent with that previously
10
reported.
10
Perreault, C.; Goudreau, S. R.; Zimmer, L. E.; Charette, A. B. Org. Lett. 2008, 10, 689.

S. R. Goudreau, D. Marcoux and A. B. Charette
S7
H
CO Me
2
CO Me
2
F
3
b
Dimethyl 2-(4-fluorophenyl)cyclopropane-1,1-dicarboxylate (3b). Purified by chromatography
on silica gel (10% EtOAc/hexane) to yield 600 mg (95% yield) of colorless oil: R 0.25 (10%
EtOAc/hexane); H NMR (400 MHz, CDCl ) δ 7.19-7.14 (m, 2H), 6.99-6.93 (m, 2H), 3.79 (s, 3H),
f
1
3
3
.39 (s, 3H), 3.19 (t, J = 8.8 Hz, 1H), 2.15 (dd, J = 8.0, 5.6 Hz, 1H), 1.74 (dd, J = 9.2, 5.2 Hz, 1H);
1
3
C NMR (100 MHz, CDCl ) δ 170.1, 166.9, 162.1 (d, J = 240 Hz), 130.3, 130.2 (d, J = 10 Hz, 2C),
3
1
1
15.1 (d, J = 20 Hz, 2C), 52.8, 52.3, 37.0, 31.7, 19.2.; IR (neat) 2954, 1723, 1514, 1436, 1277,
-
1
+
217, 1129 cm ; HRMS(ESI) calcd for C13H13FO [M+Na] : 275.0690, found 275.0695. The
4
10
spectral data were consistent with that previously reported.
H
CO Me
2
CO Me
2
Me
3c
Dimethyl 2-(4-methylphenyl)cyclopropane-1,1-dicarboxylate (3c). Purified by chromatography
on silica gel (10% EtOAc/hexane) to yield 589 mg (95% yield) of colorless oil: R 0.41 (20%
EtOAc/hexane); H NMR (400 MHz, CDCl ) δ 7.07 (s, 4H), 3.78 (s, 3H), 3.38 (s, 3H), 3.20 (t, J =
f
1
3
13
8
.6 Hz, 1H), 2.30 (s, 3H), 2.17 (dd, J = 8.0, 5.1 Hz, 1H), 1.72 (dd, J = 9.3, 5.1 Hz, 1H); C NMR
(
100 MHz, CDCl ) δ 170.2, 167.0, 136.9, 131.3, 128.8 (2), 128.2 (2), 52.6, 52.1, 37.0, 32.3, 20.9,
3
-
1
1
9.0; IR (neat) 2952, 2866, 2844, 1722, 1435, 1331, 1274, 1213, 1127 cm . The spectral data
11
were consistent with that previously reported.
H
CO Me
2
CO Me
2
3d
Dimethyl 2-butylcyclopropane-1,1-dicarboxylate (3d). Purified by chromatography on silica gel
(
10% EtOAc/hexane) to yield 504 mg (94% yield) of a colorless oil: R
f
0.52 (20% EtOAc/hexane);
1
H NMR (300 MHz, CDCl ) δ 3.74 (s, 3H), 3.71 (s, 3H), 1.94-1.83 (m, 1H), 1.51-1.24 (m, 7H), 1.21-
3
13
1
3
.09 (m, 1H), 0.87 (t, J = 7.0 Hz, 3H); C NMR (75 MHz, CDCl ) δ 170.9, 168.7, 52.5, 52.4, 33.8,
3
-1
0.9, 28.7, 28.3, 22.2, 21.3, 13.9; IR (neat) 2955, 2932, 2862, 1723, 1435, 1278, 1209, 1129 cm ;
+
18 4
HRMS (ESI) calcd for C11H O [M+Na] : 237.1097, found 237.1093.
H
CO Me
2
Ph
CO Me
2
3e
Dimethyl 2-(2-phenylethyl)cyclopropane-1,1-dicarboxylate (3e). Purified by chromatography on
silica gel (10% EtOAc/hexane) to yield 610 mg (93% yield) of a colorless oil: R 0.43 (20%
EtOAc/hexane); H NMR (400 MHz, CDCl ) δ 7.33-7.27 (m, 2H), 7.24-7.16 (m, 3H), 3.79 (s, 3H),
f
1
3
3
1
3
1
.75 (s, 3H), 2.82-2.69 (m, 2H), 1.97 (qn, J = 7.8 Hz, 1H), 1.84-1.74 (m, 1H), 1.61-1.51 (m, 1H),
13
.47-1.38 (m, 2H); C NMR (100 MHz, CDCl ) δ 170.7, 168.6, 141.3, 128.3 (4), 125.9, 52.5 (2),
3
5.1, 33.9, 30.7, 28.2, 21.2; IR (neat) 2951, 2863, 2844, 1722, 1436, 1327, 1285, 1210, 1132,
-
1
12
032 cm . The spectral data were consistent with that previously reported.
1
1
Müller, P.; Ghanem, A. Org. Lett. 2004, 6, 4347.
12
González-Bobes, F.; Fenster, M. D. B.; Kiau, S.; Kolla, L.; Kolotuchin, S.; Soumeillant, M. Adv. Synth. Catal. 2008,
50, 813.
3

S. R. Goudreau, D. Marcoux and A. B. Charette
S8
H
CO Me
2
BnO
CO Me
2
3
f
Dimethyl
2-[(benzyloxy)methyl]cyclopropane-1,1-dicarboxylate
(3f).
Purified
by
chromatography on silica gel (10% EtOAc/hexane) to yield 480 mg (69% yield) of colorless oil: R
f
1
0
3
.29 (20% EtOAc/hexane); H NMR (400 MHz, CDCl ) δ 7.34-7.20 (m, 5H), 4.48-4.38 (m, 2H),
3
.69 (s, 3H), 3.64 (s, 3H), 3.55 (dd, J = 10.5, 5.6 Hz, 1H), 3.42 (dd, J = 10.5, 7.1 Hz, 1H), 2.28-2.18
13
(
m, 1H), 1.55 (dd, J = 7.6, 4.2 Hz, 1H), 1.42 (dd, J = 9.2, 4.7 Hz, 1H); C NMR (100 MHz, CDCl )
3
δ 170.2, 168.1, 137.8, 128.2 (2), 127.5 (3), 72.7, 67.6, 52.6, 52.4, 32.6, 27.3, 18.7; IR (neat) 3030,
-
1
2
953, 2861, 1723, 1436, 1330, 1274, 1210, 1128 cm . The spectral data were consistent with that
12
previously reported.
CO Me
2
CO Me
2
3g
Dimethyl (1aS*,6aS*)-6,6a-dihydrocyclopropa[a]indene-1,1(1aH)-dicarboxylate (3g). Stirred
for 16 h. Purified by chromatography on silica gel (10% EtOAc/hexane) to yield 517 mg (84% yield)
1
of a colorless oil: R
7
f
0.38 (20% EtOAc/hexane); H NMR (400 MHz, CDCl ) δ 7.39-7.35 (m, 1H),
3
13
.20-7.12 (m, 3H), 3.76 (s, 3H), 3.40-3.23 (m, 6H), 2.68 (td, J = 6.2, 1.1 Hz, 1H); C NMR (100
MHz, CDCl ) δ 169.8, 165.9, 141.5, 140.1, 127.0, 126.7, 125.4, 124.8, 52.7, 51.9, 39.5, 39.3, 33.4,
3
-
1
3
1.5; IR (neat) 2951, 2844, 1723, 1435, 1331, 1311, 1260, 1225, 1155 cm . The spectral data
were consistent with that previously reported.
12

S. R. Goudreau, D. Marcoux and A. B. Charette
S9
1
13
H and C NMR Spectra of selected compounds

S. R. Goudreau, D. Marcoux and A. B. Charette
S10
O
O
MeO
OMe
IPh
1
f
300 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S11
O
O
MeO
OMe
IPh
1
f
7
5 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S12
O
O
i-PrO
Oi-Pr
IPh
1
a
3
00 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S13
O
O
i-PrO
Oi-Pr
IPh
1
a
7
5 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S14
O
O
EtO
OEt
IPh
1
b
3
00 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S15
O
O
EtO
OEt
IPh
1
b
7
5 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S16
O
O
t-BuO
Ot-Bu
IPh
1c
300 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S17
O
O
t-BuO
Ot-Bu
IPh
1c
75 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S18
O
O
EtO
Ot-Bu
IPh
1
e
400 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S19
O
O
EtO
Ot-Bu
IPh
1
e
100 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S20
O
O
O
O
IPh
1
g
3
00 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S21
O
O
O
O
IPh
1g
75 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S22
H
CO i-Pr
2
Ph
CO i-Pr
2
2
a
400 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S23
H
CO i-Pr
2
Ph
CO i-Pr
2
2
a
100 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S24
H
CO Et
2
Ph
CO Et
2
2
b
400 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S25
H
CO Et
2
Ph
CO Et
2
2
b
100 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S26
H
CO t-Bu
2
Ph
CO t-Bu
2
2c
4
00 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S27
H
CO t-Bu
2
Ph
CO t-Bu
2
2c
1
00 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S28
H
CO Bn
2
Ph
CO Bn
2
2
d
4
00 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S29
H
CO Bn
2
Ph
CO Bn
2
2
d
1
00 MHz, CDCl3

S. R. Goudreau, D. Marcoux and A. B. Charette
S30
H
CO t-Bu
2
Ph
CO Et
2
2
e
300 MHz, CDCl3