8516 J . Org. Chem., Vol. 66, No. 25, 2001
Wee
(Bruker 250 or Varian Unity 300 MHz) and 13C (62.5 or 75
MHz) NMR spectra were recorded from deuteriochloroform
solutions unless otherwise stated. Tetramethylsilane (δ ) 0)
was used as internal reference in 1H NMR spectra and the
CDCl3 triplet (δ ) 77.0) was used as internal reference in 13C
NMR spectra. FAB high-resolution mass spectra were obtained
using a J EOL HX110A Sector instrument. All reactions were
conducted under a static pressure of argon. Optical rotations
were measured from CHCl3 solutions, unless stated otherwise,
using a J ASCO 1000 polarimeter. Dichloromethane and 1,2-
dichloroethane were dried by distillation from CaH2; tetr-
hydrofuran was dried by distillation from sodium/benzophe-
none ketyl. All reagents were purchased from Aldrich and used
without further purification. Catalysts used: Rh2(OAc)4, Rh2-
(Cap)4, Rh2[(5R)-MEPY]4: MEPY ) methyl (5R/5S)-2-pyrro-
lidinone-5-carboxylate, Rh2[(4R)-MEOX]4: MEOX ) methyl
(4R/4S)-2-oxazolidinone-4-carboxylate, Rh 2[(4R)-MPPIM]4:
methyl (4R/4S)-1-(3-phenylpropanoyl)-2-imidazolidinone-4-car-
boxylate, Rh2[(4S)-MPPIM]4 and Cu(MeCN)4PF6.22
Gen er a l P r oced u r e for th e Rh (II)- a n d Cu (I)-Ca ta -
lyzed Rea ction of P yr r olid in yl Dia zoa ceta te (R)-5a .
Reactions were conducted in dry Cl(CH2)2Cl (0.03 M) at 60 °C,
under Ar, and using 2 mol % of Rh(II) catalyst or Cu-
(MeCN)4PF6/ligand 10 complex. Diazoacetate was added via
syringe pump over 2 h. The progress of the reaction was
monitored by TLC. After the reaction was complete, the Cl-
(CH2)2Cl was evaporated and the crude residue was filtered
through a short pad of silica gel (60 µm) using hexanes-ethyl
acetate (1:1) as eluent. The combined filtrate was concentrated,
and the mixture was analyzed using 1H NMR to determine
the ratio of product (-)-4b, dimer 8a ,b, and ether 9. Please
refer to Table 1 for details. Note that the reaction mixture from
the Rh2(OAc)4 and CuPF6/10 experiments was separated via
careful chromatography to obtain pure compounds for full
characterization purposes (vide infra).
(1S ,5S )-6-(Be n zyloxyca r b on yl)-6-a za -2-oxa -b icyclo-
[3.3.0]-3-octa n on e [(+)-4b]. Similarly a solution of (S)-
diazoacetate (160 mg, 0.553 mmol) was treated with Rh2[(S)-
MPPIM]4 (20 mg, 0.0138 mmol) in dry ClCH2CH2Cl (60 °C).
1H NMR analysis of the crude mixture again showed very little
dimer products (<1%). Chromatographic purification (2:1 and
then 1:1 hexanes-EtOAc) yielded the bicyclic lactone (110 mg,
76%). [R]D26.8 +122.9 (c 1.14, CHCl3); lit.4h [R]D24 +122.3 (c 1.42,
CHCl3). νmax: 3061, 3031, 1783, 1703, 1610, 1586, 1536 cm-1
.
1H NMR δ: 1.94-2.13 (m, 2H), 2.29 (dd, 1H, J ) 14.2 Hz, 6.1
Hz), 2.65-2.92 (m, 2H), 3.41 (ddd, 1H, J ) 11.2, 11.2, 6.2 Hz),
3.72-3.92 (m, 1H), 4.45-4.53 (m, 1H), 5.03-5.10 (m, 1H),
5.10-5.22 (m, 2H), 7.35 (s, 5H). 13C NMR δ: (29.9) 30.3, 35.4
(36.3), 44.0 (44.3), (57.5) 58.2, 67.0 (67.2), 82.8 (83.8), 127.8,
127.9, 128.1, 128.4, 136.0, (153.6) 154.1, (175.0) 175.4. FAB-
HRMS calcd for
262.1080.
C14H16NO4 (M + 1): 262.1081, Found:
(1R,4R,5R)-6-(Ben zyloxyca r bon yloxy)-4-(3-p r op en yl)-
6-a za -2-oxa -bicyclo[3.3.0]-3-octa n on e (11a ). Compound (R)-
4b (259.5 mg, 0.994 mmol) was dissolved in dry THF (6 mL)
containing HMPA (0.17 mL, 0.994 mmol), and the solution was
cooled to -78 °C, under Ar. LiHMDS (0.994 mL, 0.994 mmol,
1 M in THF) was added dropwise to the solution and the
mixture was stirred at -78 °C for 1 h. Then a mixture of allyl
bromide (0.082 mL, 0.994 mmol) and HMPA (0.17 mL, 0.994
mmol) in dry THF (4 mL) was added, and the resulting
mixture was stirred at -78 °C for 1 h and then at -45 °C for
30 min. The mixture was quenched by addition of saturated
NH4Cl (2 mL) at -45 °C, and then the mixture was allowed
to warm slowly to room temperature. EtOAc (20 mL) and brine
(10 mL) were added, and then the aqueous phase was removed.
The aqueous phase was re-extracted with EtOAc (2 × 10 mL).
The combined organic extracts were washed with brine (2 ×
10 mL), dried, filtered, and evaporated to leave a pale yellow
oil. Chromatographic purification (2:1 hexanes-EtOAc and
then 1:1 hexanes-EtOAc) of the oil yielded the allylated
lactone 11a (170.5 mg, 57%) and the diallylated compound 11b
(41 mg, 12%). For 11a : νmax: 3068, 3031, 1771, 1704, 1637,
(1R,5R)-6-(Ben zyloxyca r b on yl)-6-a za -2-oxa -b icyclo-
[3.3.0]-3-octa n on e [(-)-4b]. The (R)-5a (874 mg, 3.02 mmol)
was dissolved in dry Cl(CH2)2Cl (16 mL), and the solution was
added dropwise (syringe pump), under Ar, over a period of 2
h to a solution of Rh2[(R)-MPPIM]4 (81 mg, 0.06 mmol) in dry
ClCH2CH2Cl (8 mL) heated at 60 °C (oil bath). The cooled
reaction mixture was concentrated and filtered through a short
plug of silica gel (1:1 hexanes-EtOAc). The filtrate was
concentrated and the 1H NMR of the crude product revealed
little dimerization product (<1%) was formed. Chromato-
graphic purification (2:1 and then 1:1 hexanes-EtOAc) of the
crude product gave the (R)-bicyclic lactone (619 mg, 78%).
1589 cm-1 1H NMR δ (mixture of rotamers): 1.90-2.10 (m,
.
1H), 2.29 (dd, 1H, J ) 13.8, 5.8 Hz), 2.34-2.66 (m, 2H), 2.76
(dd, 0.4H, J ) 8.0, 5.8 Hz), 2.97 (dd, 0.6H, J ) 8.0, 5.7 Hz),
3.40 (ddd, 1H, J ) 11.5, 11.5, 6.9 Hz), 3.78 (dd, 0.5H, J ) 11.5,
9.2 Hz), 3.87 (dd, 0.5H, J ) 11.5, 9.2 Hz), 4.20 (d, 0.5H, J )
5.0 Hz), 4.27 (d, 0.5 H, J ) 5.0 Hz), 4.94-5.30 (m, 5H), 5.46-
5.64 (m, 0.4H), 5.78-5.97 (m, 0.6H), 7.37 (s, 5H). 13C NMR δ:
30.1 (30.5), 34.1, 43.9 (44.3), 46.7 (47.7), 62.2 (63.0), 67.0 (67.5),
81.7 (82.6), 118.6 (118.8), 127.8, 128.1, 128.5, 133.1, 135.8
(136.1), 153.6 (154.1), 1773 (177.7). FAB-HRMS calcd for
25.2
26
[R]D
CHCl3). νmax: 3061, 3037, 1789, 1709, 1610, 1586, 1536 cm-1
-115.5 (c 1.12, CHCl3); lit.4h [R]D -122.3 (c 4.7,
C
17H19NO4 (M + 1): 302.1392, Found: 302.1391. (1R,4R,5R)-
6-(Ben zyloxyca r bon yloxy)-4-d i(3-p r op en yl)-6-a za -2-oxa -
bicyclo[3.3.0]-3-octa n on e (11b). νmax 3074, 3030, 1771,
1703, 1641, 1586 cm-1 1H NMR δ: 1.82-2.02 (m, 1H), 2.16
.
1H NMR δ: 1.93-2.11 (m, 1H), 2.28 (dd, 1H, J ) 14.2, 6.1
Hz), 2.64-2.93 (m, 2H), 3.41 (ddd, 1H, J ) 11.2, 11.2, 6.2 Hz),
3.17-3.91 (m, 1H), 4.43-4.52 (m, 1H), 5.01-5.09 (m, 1H),
5.10-5.20 (m, 2H). 13C NMR δ: 29.9 (30.4), 35.3 (36.3), 43.9
(44.3), (57.5) 58.2, 66.9 (67.1), 82.7 (83.7), 127.7, 127.9, 128.0,
128.3, 136.0, (153.6) 153.9, (174.9) 175.3. FAB-HRMS calcd
for C14H16NO4 (M + 1): 262.1071, Found: 262.1081.
:
.
(dd, 1H, J ) 13.2, 4.4 Hz), 2.22-2.60 (m, 4H), 3.07-3.23 (m,
1H), 3.90 (dd, 0.6H, J ) 13.2, 8.8 Hz), 3.96 (dd, 0.4H, J ) 13.2,
8.8 Hz), 4.52 (d, 0.4H, J ) 7.9 Hz), 4.61 (d, 0.6H, J ) 7.9 Hz),
4.82-5.29 (m, 7H), 5.50-5.69 (m, 0.5H), 5.70-5.95 (m, 1.5H),
7.30-7.45 (m, 5H). 13C NMR δ: 31.2 (31.8), 36.7, 41.7 (41.9),
44.5 (44.7), 49.8 (50.4), 64.4 (65.4), 67.3 (67.7), 80.3 (81.0), 117.5
(117.8), 120.3, 127.9, 128.1, 128.4, 128.7, 131.5 (131.7), 132.8
(133.3), 135.6 (136.1), 154.1 (155.0), 179.0. FAB-HRMS calcd
for C20H24NO4 (M + 1): 342.1705, Found: 342.1716.
Bis[(R)-3-p yr r olid in yl]m a lea te (7a ). νmax
: 3061, 3055,
1
1715, 1641, 1586 cm-1. H NMR δ: 2.00-2.20 (m, 2H), 3.35-
3.82 (m, 8H), 5.20 (s, 4H), 5.30-5.45 (m, 2H), 6.25 (s, 2H),
7.27-7.42 (m, 10H). FAB-HRMS calcd for C28H31N2O8 (M +
1): 523.2082, Found: 523.2092.
(3R)-1-(Ben zyloxycar bon yl)-3-h ydr oxy-2-[2-(4-pen ten yl-
1-ol)]p yr r olid in e (12a ). A solution of 11a (167 mg, 0.555
mmol) in 95% ethanol (5 mL) was treated with NaBH4 (84 mg,
2.22 mmol), under Ar. The mixture was stirred at room
temperature for 22 h and then cooled to 0 °C. Glacial acetic
acid was carefully added to the reaction mixture, and when
effervescence stopped, the mixture was concentrated. CH2Cl2
(10 mL) was added to the residue and followed by solid
anhydrous K2CO3 and Na2SO4. The mixture was allowed to
stand at room temperature for 1 h and then filtered and
concentrated. The residual oil was chromatographed (1:1
hexanes-EtOAc and then EtOAc) to yield the diol 12a as a
viscous oil (148 mg, 86%). νmax: 3622-3117, 3062, 3026, 1674,
Bis-[(R)-3-p yr r olid in yl]fu m a r a te (7b). νmax: 3068, 3031,
1709, 1653 cm-1 1H NMR δ: 2.05-2.20 (m, 4H), 3.45-3.72
.
(m, 8H), 5.15 (s, 4H), 6.85 (s, 2H), 7.30-7.45 (m, 10H). FAB-
HRMS calcd for C28H31N2O8 (M + 1): 523.2082, Found:
523.2079.
(R)-3-P yr r olid in yl
[(R)-3-p yr r olid in yloxyca r b on yl-
m eth yloxy]a ceta te (9). νmax: 3061, 1752, 1702, 1586 cm-1
.
1H NMR δ: 2.05-2.20 (m, 4H), 3.40-3.70 (m, 8H), 4.25 (s,
4H), 5.15 (s, 4H), 5.35-5.45 (m, 2H), 7.30-7.45 (m, 10H). FAB-
HRMS calcd for C28H33N2O9 (M + 1): 541.2186, Found:
541.2178.
(22) Kubas, G. J . Inorg. Synth. 1979, 19, 90.
1583, 1502 cm-1 1H NMR δ: 1.80-2.50 (m, 5H, 2H-4, CH,
.