) 11 Hz), 3.53 (3H, d, J HP ) 11 Hz), 3.41 (1H, app t, J HH ) 7.6
Hz), 3.20 (1H, m), 2.92 (1H, m), 2.65 (1H, m), 1.47 (4.5H, s),
1.46 (4.5H, s); 13C NMR (CDCl3) 168.9, 168.5 167.9, 166.7, 159.9,
152.5 (d, J CP ) 4.9 Hz), 139.9, 129.7, 121.8 (d, J CP ) 3.8 Hz),
118.8 (d, J CP ) 183 Hz), 115.1 (d, J CP ) 3.5 Hz), 112.3, 82.9 (x2),
56.1, 55.9, 55.3, 52.7, 52.5 (d, J CP ) 5 Hz), 52.4 (d, J CP ) 5 Hz),
46.1 (d, J CP ) 11 Hz), 45.8 (d, J CP ) 11 Hz),38.3, 28.1(x2); 31P
NMR (CDCl3) δ 20.6; HRMS (FAB, NBA/CsI, [M + Cs]+) calcd
for C21H31O8PCs 575.0810, found 575.0820.
3-(ter t-Bu toxyca r bon yl)-4-[(3-m eth oxyp h en yl)m eth yl]-
d ih yd r o-2(3H)-fu r a n on e 13. The vinyl phosphonate 11d (0.873
g, 1.97 mmol) was dissolved in anhydrous MeOH (16 mL) and
CH2Cl2 (20 mL), and the resulting solution was cooled to -78
°C. O3 was bubbled into the solution until the starting material
had been consumed (TLC). The reaction flask and solution were
flushed with argon to remove residual O3, and then NaBH4
(0.448 g, 11.8 mmol) was added. The mixture was allowed to
warm to room temperature, and stirring was continued over-
night. The reaction mixture was washed twice with H2O, and
the aqueous layer was re-extracted with CH2Cl2. The combined
organic layers were dried over anhydrous Na2SO4, and the
solution was concentrated in vacuo. The crude product was
purified by chromatography (SiO2, EtOAc/hexanes 1:1) to give
the lactone 13 (0.34 g, 57%): IR (neat) 1780, 1729 cm-1; 1H NMR
(CDCl3) δ 7.21 (1H, t, J ) 7.9 Hz), 6.73 (3H, m), 4.38 (1H m),
3.93 (1H, m), 3.77 (3H, s), 3.20 (2H, m), 2.76 (2H, m), 1.38 (9H,
s); 13C NMR (CDCl3) δ 171.3, 166.4, 159.9, 138.9, 129.9, 121.2,
114.7, 112.3, 82.7, 71.2, 55.2, 53.0, 41.5, 37.9, 27.8; HRMS (EI,
M+) calcd for C17H22O5 306.1467, found 306.1469.
cleophilic attack (i.e., overall retention). It is believed that
the diene 12 is formed from the π-allyl intermediate via
a base-induced elimination,21 a process that is known to
compete with addition.22 The substituted malonate 10c
is probably too bulky and acts as a base rather than a
nucleophile. Furthermore, the conjugation of the aromatic
ring to the diene makes elimination favorable.
In summary, the palladium-catalyzed addition of tert-
butyl methyl malonate 10d to (1R)-phosphono allylic
carbonate 3d results in the formation of the vinyl
phosphonate 11d . The vinyl phosphonate 11d , formed
with retention of configuration, was converted to the
known (-)-enterolactone precursor (4R)-4-[(3-methox-
yphenyl)methyl]dihydro-2-(3H)-furnanone.
Exp er im en ta l Section
(()- or (R)-(2E)-Dim eth yl [1-(Meth oxyca r bon yloxy)-4-(3-
m eth oxyp h en yl)-2-bu ten yl]p h osp h on a te 3d . Second-genera-
tion Grubbs catalyst (0.284 g, 0.335 mmol) was dissolved in
CH2Cl2 (10 mL). Phosphonate 3a (1.5 g, 6.7 mmol) and 3-(3-
methoxyphenyl)propene 6 (1.49 g, 10.0 mmol) were added, and
the reaction flask was placed in a preheated oil bath and heated
at 40 °C for 12 h. The reaction mixture was allowed to cool, and
then the solvent was evaporated in vacuo. The crude product
was purified by chromatography (SiO2, CH2Cl2/EtOAc 20:80) to
give dimethyl [1-(methoxycarbonyloxy)-4-(3-methoxyphenyl)-2-
butenyl]phosphonate 3d as a pale yellow oil (1.56 g, 68%): IR
(neat, NaCl) 1755 cm-1; 1H NMR (CDCl3) δ 7.20 (1H, t, J ) 7.8
Hz), 6.74 (3H, m), 6.07 (1H, m), 5.65 (1H, m), 5.49 (1H, dd, J HH
) 7.9 Hz, J HP ) 13 Hz), 3.81 (3H, s), 3.79 (6H, d, J HP ) 11 Hz),
3.78 (3H, s), 3.42 (2H, m); 13C NMR (CDCl3) δ 160.0, 154.9 (d,
J CP ) 9.5 Hz), 140.7 (d, J CP ) 2.3 Hz), 136.4 (d, J CP ) 12.3 Hz),
129.7, 122.1 (d, J CP ) 3.9 Hz), 121.1, 114.4, 112.0, 72.9 (d, J CP
) 169 Hz), 55.6, 55.3, 55.1 (d, J CP ) 7.1 Hz), 53.9 (d, J CP ) 6.5
Hz), 38.8 (d, J CP ) 1.3 Hz); 31P NMR (CDCl3) δ 20.7; HRMS (EI,
M+) calcd for C15H21O7P 344.1025, found 344.1027.
Gen er a l P r oced u r e for th e Ad d ition of Ma lon a tes to
Allylic Ca r bon a tes 3b-d . NaH (3.47 mmol) was suspended
in anhydrous THF (16 mL), and then the malonate (3.47 mmol)
in THF (1 mL) was added. The mixture was stirred at room
temperature for 3-4 min. The phosphonate (2.9 mmol) was
added, followed by Pd(PPh3)4 (0.09 mmol, 3 mol %). The reaction
flask was placed in a preheated oil bath and heated at 70 °C for
1 h. The reaction mixture was allowed to cool, and then it was
partitioned between brine and Et2O. After separation, the
aqueous layer was re-extracted with Et2O and the combined
organic layers were dried over anhydrous Na2SO4. The solvent
was evaporated in vacuo to give the crude product.
4-[(3-Meth oxyph en yl)m eth yl]dih ydr o-2(3H)-fu r an on e 14.
The lactone 13 (0.032 g, 0.11 mmol) was dissolved in DMSO (2
mL) and H2O (1 drop), and then LiCl (0.0089 g, 0.21 mmol) was
added. The reaction mixture was heated at 140 °C for 17 h. The
reaction mixture was cooled, diluted with H2O, and extracted
with EtOAc (3×). The combined EtOAc extracts were washed
with 1 N HCl, saturated NaHCO3, and brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. The crude
product was purified by chromatography (SiO2, EtOAc/hexanes
50:50) to give the lactone 14 (0.014 g, 65%): IR (neat) 1778 cm-1
;
1H NMR (CDCl3) δ 7.24 (1H, t, J ) 7.9 Hz), 6.8 (3H, m), 4.34
(1H, dd, J ) 6.9, 9.1 Hz), 4.03 (1H, dd, J ) 6.0, 9.1 Hz), 3.80
(3H, s), 2.84 (1H, m), 2.76 (2H, m), 2.61 (1H, dd, J ) 7.9, 17
Hz), 2.29 (1H, dd, J ) 6.9, 17 Hz), 13C NMR (CDCl3) δ 177.0,
160.1, 140.0, 130.0, 121.1, 114.8, 112.0, 72.8, 55.4, 39.1, 37.2,
34.4; HRMS (EI, M+) calcd for C12H14O3 206.0943, found
206.0944. The lactone had 92% ee determined by HPLC, [R]D
+6.7 (1.1, CHCl3) (lit.3c (4R)-4-[(3-m eth oxyp h en yl)m eth yl]-
d ih yd r o-2(3H)-fu r a n on e [R]D +6.7 (1.66, CHCl3).
Ack n ow led gm en t. We are grateful to the donors
of the Petroleum Research Fund, administered by the
American Chemical Society (34428-AC1), for financial
support of this project and the UMSL Graduate School
for a fellowship for B.Y. We are also grateful to the NSF,
the US DOE, and the University of Missouri Research
Board for grants to purchase the NMR spectrometers
(CHE-9318696, CHE-9974801, DE-FG02-92-CH10499)
and mass spectrometer (CHE-9708640) used in this
work. We thank Brad Rowe and J eff Scholten for some
preliminary investigations, Mr. J oe Kramer and Prof.
R. E. K. Winter for mass spectra, and Anyu He for
synthesis of dimethyl (1-hydroxy-2-propenyl)phospho-
nate.
Ad d ition of ter t-Bu tyl Meth yl Ma lon a te 10d to Dim eth yl
[1-(Meth oxyca r bon yloxy)-4-(3-m eth oxyp h en yl)-2-bu ten yl]-
p h osp h on a te 3d . NaH (0.139 g, 3.48 mmol) in THF (16 mL),
malonate 10d (0.61 mL, 3.48 mmol) in THF (1 mL), phosphonate
3d (0.99 g, 2.9 mmol), and Pd(PPh3)4 (0.101 g, 0.09 mmol). The
crude product was purified by chromatography (SiO2, hexane/
acetone 50:50) to give a diastereoisomeric (50:50) mixture of
malonate adducts 11d as a pale yellow oil (1.08 g, 84%): IR
(neat) 1728 cm-1; 1H NMR (CDCl3) δ 7.18 (1H, t, J HH ) 8.0 Hz),
6.72 (3H, m), 6.63 (1H, m), 5.48 (1H, m), 3.78 (3H, s), 3.75 (1.5H,
s), 3.72 (1.5H, s), 3.63 (1.5H, d, J HP ) 11 Hz), 3.62 (1.5H, d, J HP
(20) (a) Hegedus, L. S. Transition Metals in the Synthesis of Complex
Organic Molecules, 2nd ed.; University Science Books: Sausalito, CA,
1999. (b) Tsuji, J . Palladium Reagents and Catalysts; J ohn Wiley &
Sons: Chichester, 1995. (c) Heck, R. F. Palladium Reagents in Organic
Synthesis; Academic Press: London, 1987. (d) Trost, B. M. Acc. Chem.
Res. 1980, 13, 385.
(21) (a) Tsuji, J .; Yamakawa, T.; Kaito, M.; Mandai, T. Tetrahedron
Lett. 1978, 2075. (b) Matsushita, H.; Negishi, E.-I. J . Org. Chem. 1982,
47, 4161.
Su p p or tin g In for m a tion Ava ila ble: Experimental and
characterization data for compounds 1a , (R)1a , (R)1b, 3a , 3b,
(R)3d , 6, 11a -c, and 12, spectra for compounds 1a , 1b, 3a ,
3b, 3d , 6, 11a -d , and 12-14, and HPLC data for compounds
1b, 3b, 11a , 3d , and 14. This material is available free of
(22) (a) Trost, B. M.; Verhoeven, T. R. Fortunak, J . M. Tetrahedron
Lett. 1979, 2301. (b) Shimizu, I.; Yamada, T.; Tsuji, J . Tetrahedron
Lett. 1980, 21, 3199.
J O035795H
2862 J . Org. Chem., Vol. 69, No. 8, 2004