8612 J . Org. Chem., Vol. 63, No. 23, 1998
Notes
eomers. The NMR spectra are superimpositions of those of the
two diastereomers in an approximately 3:1 ratio. Spectra for
the major diastereomer follow. 1H NMR (CDCl3): δ 0.80-0.88
(1H, dt, J 1 ) 8.4 Hz, J 2 ) 5.4 Hz), 0.93-1.09 (1H, m), 1.15-
1.30 (1H, m), 1.30-1.35 (3H, m), 1.95-2.06 (1H, m), 2.30-2.52
(1H, m), 7.08-7.29 (5H, m), 11.2-11.8 (1H, bs). 13C NMR
(CDCl3): δ 14.0, 16.1, 22.4, 25.6, 43.9, 125.6, 126.2, 128.2, 142.3,
181.6.
1-[[[(tr a n s-2-P h en ylcyclop r op yl)et h yl]ca r b on yl]oxy]-
2(1H)-p yr id in eth ion e (10d ). To a solution of acid 10c (160
mg, 0.842 mmol) and 2,2′-dipyridyl disulfide bis-N-oxide (1.1
equiv, 234 mg, 0.93 mmol) in dry CH2Cl2 (10 mL) in a flame-
dried flask wrapped with aluminum foil was added Ph3P (1.1
equiv, 244 mg, 0.93 mmol) at room temperature under nitrogen.
The reaction mixture was stirred for 3 h and then treated with
10 mL of a 10% aqueous Na2CO3 solution. The organic layer
was separated, and the aqueous layer was extracted with 10
mL of CH2Cl2. The combined organic extracts were washed with
a saturated aqueous NaCl solution (10 mL), dried over MgSO4,
and concentrated under reduced pressure. Column chromatog-
raphy of the residue on silica gel (hexanes/EtOAc, 7/3, v/v) under
subdued light gave PTOC ester 10d (170 mg, 0.57 mmol, 67.7%)
as a mixture of diastereomers. The NMR spectra are superim-
positions of those of the two diastereomers in an approximately
3:1 ratio. Spectra for the major diastereomer follow. 1H NMR
(CDCl3): δ 0.95 (1H, m), 1.12 (1H, m), 1.36-1.48 (1H, m), 1.52
(3H, d, J ) 7.2 Hz), 2.10-2.12 (1H, m), 2.36-2.48 (1H, m), 6.55-
6.60 (1H, dt, J 1 ) 6.9 Hz, J 2 ) 1.8 Hz), 7.08-7.30 (6H, m), 7.42-
F igu r e 2. Relative rate constants at 20 °C for ring openings
of 1°, 2°, and 3° radicals for each series.
at 20 °C are given. The data for radicals 20 is from a
variety of indirect kinetic studies,2,4,33 and those for
radicals 21 were obtained by direct LFP measurements.31
Good internal consistency of the relative rate constants
for these series is found even though radicals 1a , 10a ,
and 11a ring open 3 orders of magnitude faster than
radicals 20 and 21. The consistent trends appear to be
in line with computational results that indicate that
electronic effects of methyl substitution in the secondary
alkyl radical 20 (R ) Me, R′ ) H) are minor in compari-
son to steric effects.34
Exp er im en ta l Section
7.45 (0.7H, dd, J 1 ) 7.2 Hz, J 2 ) 1.5 Hz), 7.66-7.69 (1H, J 1
)
6.9 Hz, J 2 ) 1.8 Hz). 13C NMR (CDCl3): δ 14.4, 16.3, 22.7, 25.5,
42.4, 112.5, 125.8, 125.9, 128.3, 133.4, 137.4, 137.5, 141.7, 171.1,
175.7.
Gen er a l Meth od s. Commercially available reagents were
used as received. All moisture sensitive reactions were carried
out in flame-dried glassware under a nitrogen atmosphere. THF
was distilled under a nitrogen atmosphere from sodium and
benzophenone ketyl. Methylene chloride was distilled under a
nitrogen atmosphere from phosphorus pentoxide.
2-Meth yl-2-(tr a n s-2-p h en ylcyclop r op yl)p r op ion ic Acid
(11c). To a solution of 1528 (2.55 g, 12.5 mmol) and diethylzinc
(75.0 mL, 1.0 M in hexanes, 75.0 mmol) in CH2Cl2 (200 mL) at
-20 °C under a nitrogen atmosphere was added CH2I2 (12.1 mL,
150.2 mmol) slowly via syringe. The mixture was allowed to
warm to room temperature gradually, and after a total of 16 h,
the suspension was poured into a saturated aqueous NH4Cl
solution (300 mL). The mixture was extracted with CH2Cl2 (3
× 200 mL). The combined organic layers were washed with
water (200 mL) and brine (200 mL), dried over MgSO4, filtered,
and concentrated in vacuo. The crude product was dissolved in
CH2Cl2 (100 mL), and 3-chloroperoxybenzoic acid (2.16 g, 12.5
mmol) was added. The mixture was stirred for 8 h at room
temperature and then diluted with additional CH2Cl2 (200 mL).
The mixture was washed with saturated aqueous NaHCO3 (200
mL), water (200 mL), and brine (200 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The crude product was
chromatographed on silica gel (10% ethyl acetate in hexanes)
to afford the cyclopropyl ester (1.41 g, 6.46 mmol, 52%) as a clear,
colorless oil. 1H NMR (CDCl3): δ 0.87 (1H, dt, J 1 ) 8.7 Hz, J 2
) 5.4 Hz), 0.94-1.01 (1H, m), 1.17 (3H, s), 1.18 (3H, s), 1.33-
1.39 (1H, m), 1.90 (1H, dt, J 1 ) 9.3 Hz, J 2 ) 5.4 Hz), 3.69 (3H,
s), 7.07-7.17 (3H, m), 7.22-7.29 (2H, m). 13C NMR (CDCl3): δ
11.3, 19.1, 23.2, 23.4, 31.0, 41.7, 51.8, 125.5, 126.2 (2C), 128.2
(2C), 142.9, 177.8. HRMS: calcd for C14H18O2, 218.1307; found,
218.1304.
A solution of the above ester (0.32 g, 1.47 mmol) and LiOH‚
H2O (0.62 g, 14.7 mmol) in water (5 mL) and methanol (20 mL)
was stirred at room temperature for 6 h. The solvents were
removed in vacuo, and the resulting white solid was dissolved
in water (25 mL). This solution was made acidic (concentrated
HCl) and then extracted with CH2Cl2 (3 × 25 mL). The
combined organic layers were washed with brine (50 mL), dried
over Na2SO4, filtered, and concentrated in vacuo to afford 11c
(0.25 g, 1.22 mmol, 83%) as a white solid. Mp: 60-61 °C. 1H
NMR (CDCl3): δ 0.94 (1H, dt, J 1 ) 9.0 Hz, J 2 ) 5.4 Hz), 1.04-
1.11 (1H, m), 1.23 (3H, s), 1.26 (3H, s), 1.44-1.50 (1H, m), 1.99
(1H, dt, J 1 ) 9.0 Hz, J 2 ) 5.1 Hz), 7.14-7.34 (5H, m), 11.95
(1H, bs). 13C NMR (CDCl3): δ 11.5, 19.2, 22.8, 23.3, 30.7, 41.6,
125.6, 126.2 (2C), 128.3 (2C), 142.8, 184.5. HRMS: calcd for
C13H16O2, 204.1150; found, 204.1155.
NMR spectra were acquired at 300 and 75 MHz for 1H and
13C, respectively. Gas chromatographic analyses were performed
using flame ionization detection with 15 m × 0.54 mm bonded
phase SE-54 and Carbowax columns. Gas chromatography/mass
spectral (GC/MS) analyses were performed using a Hewlett-
Packard model 5890 GC interfaced to a Hewlett-Packard model
5971 mass selective detector (30 m × 0.25 mm capillary bonded
phase Carbowax column, Alltech). High-resolution mass spec-
tral analyses were performed by the Central Instrumentation
Facility at Wayne State University (Detroit, MI). Melting points
are uncorrected. Radial chromatography was performed on
plates coated with TLC grade silica gel with gypsum binder and
fluorescent indicator.
2-(tr a n s-2-P h en ylcyclop r op yl)p r op ion ic Acid (10c).
A
solution of methyl (trans-2-phenylcyclopropyl)acetate27 (14) (1.30
g, 6.83 mmol) in THF (50 mL) under a nitrogen atmosphere was
cooled to -78 °C. To this was added a solution of LHMDS (1.0
M in THF, 7.0 mL, 7.00 mmol). After 15 min, iodomethane (1.3
mL, 20.2 mmol) was added. The mixture was allowed to warm
gradually to room temperature, and after 16 h, the reaction
mixture was poured into a saturated, aqueous NH4Cl solution
(100 mL) and extracted with ether (3 × 50 mL). The combined
organic phase was washed with water (75 mL) and brine (75
mL), dried over MgSO4, filtered, and concentrated in vacuo. The
crude product was chromatographed on silica gel (10% ethyl
acetate in hexanes) to afford
a mixture of diastereomers,
inseparable by GC, of methyl 2-(trans-2-phenylcyclopropyl)-
propionate (0.58 g, 2.84 mmol, 42%) as a clear, colorless oil.
Reduction of the inseparable mixture of esters with LAH
afforded a mixture of diastereomeric alcohols in a 3:1 ratio as
determined by GC. GC/mass spectral analysis of the mixture
showed that both isomers had (M+) at m/z ) 176.
Hydrolysis of a mixture of diastereomers of the above ester
(180 mg, 0.882 mmol) with LiOH‚H2O (185 mg, 4.41 mmol) in
methanol (9 mL) and H2O (3 mL) at room temperature gave the
corresponding acid 10c (161 mg, 96%) as a mixture of diaster-
(33) Bowry, V. W.; Lusztyk, J .; Ingold, K. U. J . Am. Chem. Soc. 1991,
113, 5687-5698. Engel, P. S.; He, S. L.; Banks, J . T.; Ingold, K. U.;
Lusztyk, J . J . Org. Chem. 1997, 62, 1210-1214.
(34) Martinez, F. M.; Schlegel, H. B.; Newcomb, M. J . Org. Chem.
1998, 63, 1226-1232.
1-[[[1-Meth yl(tr a n s-2-ph en ylcyclopr opyl)eth yl]car bon yl]-
oxy]-2-(1H)-p yr id in eth ion e (11d ). To a solution of acid 11c
(220 mg, 1.08 mmol) and 2,2′-dipyridyl disulfide bis-N-oxide (1.1
equiv, 299 mg, 1.19 mmol) in dry CH2Cl2 (10 mL) in a flame-