Muthukrishnan et al.
JOCArticle
SCHEME 7
3. Preparation of Starting Materials. Preparation of 1a. A
solution of o-bromotoluene (7.4 g, 0.043 mol) in anhydrous
tetrahydrofuran (THF) (50 mL) was added dropwise over
30 min to magnesium turnings (1.05 g, 0.043 mol) while stirring
to form the Grignard reagent, which was grayish-yellow in
color. Simultaneously, to a solution of anhydrous LiBr (7.36
g, 0.086 mol) in anhydrous THF (35 mL) was added anhydrous
CuBr (6.15 g, 0.043 mol), which resulted in a green solution. The
Grignard reagent was added to the green CuBr solution drop-
wise over 20 min. To the resulting slurry, a solution of β-
carbomethoxypropionyl chloride (6.45 g, 0.043 mol; prepared
from succinic anhydride according to the literature procedure in
90% yield48) in anhydrous THF (10 mL) was added over 15 min.
A highly exothermic reaction ensued, and the resulting solution
was stirred further for 20 min at room temperature. The reaction
was quenched with saturated aqueous ammonium chloride
solution and extracted with ethyl acetate (3 ꢀ 40 mL). The
organic layer was washed with brine, dried over anhydrous
magnesium sulfate, and evaporated to obtain a red oil. Upon
purification of the oil by column chromatography (silica gel
2.4 cm ꢀ 25 cm, 85:15 hexane/ethyl acetate), 1a was obtained as
a pale yellow oil (3.5 g, 0.017 mol, yield 40%). IR (CHCl3) 3020,
Photolysis of 1a in Oxygen-Saturated Methanol. Ester 1a
(84 mg, 0.41 mmol) was dissolved in methanol (20 mL), and
the solution was purged with oxygen for 20 min. Hexadecane (10 μL)
was added as an internal standard. The resulting solution was
irradiated through a Pyrex filter for 28 h using a medium-
pressure mercury arc lamp. The reaction mixture was analyzed
with GC-MS, which showed formation of two products, 5
(58%) and 6 (12%), as well as the remaining starting material
(∼30%). Comparison of GC-MS and 1H NMR spectra of
commercially available 6 verified its structure.
Because 5 decomposes on silica column, we derivatized it to
form acetal 12 following the procedure described in the
literature.50 In this procedure, we selectively protected the
aldehyde without affecting the ketone or the ester moieties. A
product mixture (80 mg containing 58% of the aldehyde 5, 46
mg, 0.21 mmol based on GC-MS) was dissolved in dry CCl4
(5 mL), added to a stirred suspension of anhydrous acidic
alumina (100 mg, 2 mmol) and dry ethylene glycol (15 mg, 0.24
mmol) in 5 mL of anhydrous CCl4, and refluxed for 8 h under
argon. The resulting mixture was filtered, evaporated, and
purified by preparative silica gel plate with ethyl acetate/
hexane/dichloromethane as the eluent (1:2:2) to obtain 12 as
1
1735, 1686, 1218 cm-1
;
1H NMR (250 MHz, CDCl3) δ
a colorless liquid (34 mg, 0.13 mmol, 66% yield). H NMR
7.70-7.73 (m, 1H), 7.23-7.38 (m, 3H), 3.71 (s, 3H), 3.23 (t,
7.2 Hz, 2H), 2.75 (t, 7.2 Hz, 2H), 2.50 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3) δ 202.0, 173.4, 138.3, 137.4, 132.0, 131.5,
128.6, 125.7, 51.8, 36.1, 28.2, 21.3 ppm; MS (EI) m/z (relative
intensity) 206 (Mþ, 5), 175 (10), 145 (5), 131 (5), 119 (100), 91
(100), 65 (50); HRMS m/z calcd for C12H14O3Na, [M þ Na]þ
229.0841, found 229.0846.
(400 MHz, CDCl3) δ 7.72-7.43 (m, 4H), 6.23 (s, 1H), 4.01
(pseudo d, 4H, 2.8 Hz), 3.70 (s, 3H), 3.21 (t, 4 Hz, 2H), 2.76 (t,
2H) ppm; 13C NMR (100 MHz, CDCl3) δ 202.9, 173.3, 136.6,
130.9, 128.8, 127.4, 126.9, 100.9, 72.2, 65.3 (2C), 51.7, 37.1,
28.4. HRMS m/z calcd 287.0895 for C14H16O5Na, found
287.0905.
Photolysis of 1b in Argon-Saturated Solutions. Photolysis of
1b (0.02 M) in dichloromethane for 7 days did not result in any
new products.
4. Product Studies. Photolysis of 1a in Argon-Saturated
Methanol. A degassed solution of 1a (84 mg, 0.41 mmol) in
methanol (20 mL) was irradiated through a Pyrex filter (>300
nm) for 72 h using a medium-pressure mercury arc lamp. After
the majority of the starting material was depleted (TLC, ethyl
acetate/hexane, 1:4), the solvent was evaporated, and the photo-
products were separated by column chromatography (ethyl
acetate/hexane) to give recovered 1 (5 mg, 0.024 mmol, 6%
yield) and 4 (42 mg, 0.24 mmol, 59% yield) as an oil. The
spectroscopic data for 4 is similar to those of an analogous
Photolysis of 1b in Oxygen-Saturated Dichloromethane. Ester
1b (110 mg, 0.4 mmol) was dissolved in dichloromethane (20
mL), and the solution was purged with oxygen for 20 min. The
resulting solution was irradiated through Pyrex filter for 48 h
using a medium pressure mercury arc lamp. The reaction
mixture was analyzed with GC-MS that showed formation of
a trace amount (∼1-2%) of 4-[2-(1-hydroxy-1-methyl-ethyl)-4-
isopropyl-phenyl]-4-oxo-butyric acid, methyl ester. The product
was isolated on a silica column using 20% ethyl acetate in
1
lactone.49 IR (CHCl3) 3020, 1772, 1215 cm-1; H NMR (250
1
MHz, CDCl3) δ 7.37-7.18 (m, 4H), 3.64 (d, 14 Hz, 1H), 3.46 (d,
14 Hz, 1H), 2.75-2.71 (m, 2H); 2.80-2.50 (m, 2H) ppm; 13C
NMR (60 MHz, CDCl3) δ 176.5, 145.6, 141.0, 130.8, 128.1,
123.8, 121.3, 88.0, 45.6, 32.1, 29.4 ppm; MS (EI) m/z (relative
intensity) 173 ([M - H]þ, 50), 158 (10), 145 (100), 131 (80), 118
(80), 102 (15), 89 (80), 77 (15); HRMS m/z calcd for C11H11O2,
[M þ H]þ calcd 175.0759, found 175.0736.
hexane to give 1.5 mg (0.004 mmol) of the product: H NMR
δ 7.56-7.50 (m, 2H), 7.34 (m, 1H), 3.71 (s, 3H), 3.44-3.34 (m,
1H), 3.18 (t, J = 7 Hz, 2H), 2.75 (t, J = 7 Hz, 2H), 1.59 (s, 6H),
1.24 (d, J = 7 Hz, 6H) ppm; 13C NMR δ 203.5, 173.3, 152.1,
148.0, 136.7, 127.5, 122.4, 121.6, 72.6, 51.8, 37.2, 31.7, 29.7, 28.2,
24.2 ppm; IR 3401, 2917, 2848, 1738, 1689, 1603, 1460, 1403
cm-1; HRMS C17H24O4Na [M þ Na]þ calcd 315.1572, exptl
315.1578
(48) Cason, J. Org. Synth. 1945, 25.
(49) Sankaranarayanan, J.; Mandel, S. M.; Krause, J. A.; Gudmunds-
dottir, A. D. Acta Crystallogr., Sect. E: Struct. Rep. Online 2007, E63, o721–
o723.
(50) Kamitori, Y.; Hojo, M.; Masuda, R.; Yoshida, T. Tetrahedron Lett.
1985, 26, 4767–4770.
1400 J. Org. Chem. Vol. 75, No. 5, 2010