Davis et al.
(2 × 4 mL) and the combined organic phases were dried
(Na2SO4) and concentrated. Flash chromatography (1:1 EtOAc/
hexane) gave 0.066 g (85%) of a white solid, mp 85-86 °C;
Meth yl (2S,5R)-(-)-N-(ter t-Bu tyloxyca r bon yl)-3-oxo-5-
(ter t-bu tyl)p yr r olid in e-2-ca r boxyla te (8). In a 100-mL,
one-necked, round-bottomed flask equipped with a magnetic
stirring bar and an argon-filled balloon was placed (R)-(-)-7
(0.78 g, 2.38 mmol) in CH2Cl2 (30 mL). To the solution was
added Rh2(OAc)4 (0.050 g, 0.1 mmol), and the reaction mixture
was stirred for 2.5 h at room temperature and then concen-
trated. Chromatography (5%-20% EtOAc/hexane) afforded
0.69 g (97%) of a white solid, mp 119-120 °C; [R]20D -114.0 (c
1.3, CHCl3); IR (neat) 2959, 1753, 1715 cm-1; 1H NMR δ 4.64-
4.74 (br, 1 H), 4.12-4.20 (br, 1 H), 3.84 (s, 3 H), 2.54 (m, 1 H),
[R]20 +143.3 (c 1.0, CHCl3); IR (neat) 3198, 2956, 1745, 1718
D
cm-1; 1H NMR δ 7.57 (d, J ) 6.8 Hz, 2 H), 7.28 (d, J ) 6.8 Hz,
2 H), 4.04 (d, J ) 7.6 Hz, 1 H), 3.74 (s, 3 H), 3.73 (m, 1 H),
3.59 (d, J ) 12.4 Hz, 1 H), 3.57 (d, J ) 12.4 Hz, 1 H), 2.91 (dd,
J ) 3.2, 13.6 Hz, 1 H), 2.82 (dd, J ) 5.6, 13.6 Hz, 1 H), 2.41 (s,
3 H), 0.95 (s, 9 H); 13C NMR δ 201.7, 168.3, 143.5, 141.8, 130.0,
125.7, 61.5, 52.8, 50.3, 46.0, 35.8, 26.9, 21.8. HRMS calcd for
C
17H25NO4S (M + Na) 362.1410, found 362.1402.
2.53 (d, J ) 18 Hz, 1 H), 1.44-1.50 (br, 9 H), 0.94 (s, 9 H); 13
C
On e-Step Meth od . In a 500-mL, one-necked, round-bot-
NMR δ 204.4, 167.1, 155.9, 81.8, 66.9, 62.6, 53.0, 41.0, 37.1,
28.8, 26.7. HRMS calcd for C15H25NO5 (M + Na) 322.1630,
found 322.1626.
tomed flask equipped with a magnetic stirring bar, a rubber
septum, and an argon inlet was placed THF (120 mL) and
NaHMDS (45.6 mL, 1.0 M solution in THF). The solution was
cooled to -78 °C, methyl acetate (3.10 mL, 38.0 mmol) was
added via syringe, and the reaction mixture was stirred at this
temperature for 1 h. At this time anhydrous ether (100 mL)
was added followed by (SS,R)-(+)-3 (1.70 g, 7.6 mmol) in THF
(15 mL). The reaction mixture was stirred at -78 °C for 1 h,
warmed to -20 °C for another 3 h, and quenched at -78 °C
with saturated aqueous NH4Cl (40 mL). The solution was
extracted with ethyl acetate (3 × 100 mL), and the combined
organic phases were dried (Na2SO4) and concentrated. Puri-
fication was by flash chromatography (1:1 EtOAc/hexane) to
give 2.4 g (93%, >96% de) of an oil.
Meth yl (SS,R)-(+)-2-Dia zo-6,6-d im eth yl-3-oxo-N-(p-tol-
u en esu lfin yl)-5-a m in oh ep ta n oa te (6). In an oven-dried
100-mL, one-necked, round-bottomed flask equipped with a
magnetic stirring bar, a rubber septum, and an argon balloon
was placed 2.04 g (6.0 mmol) of (SS,R)-(+)-5 and 4-carboxyl-
benzenesulfonyl azide (4-CBSA, 1.5 g, 6.6 mmol) in acetonitrile
(40 mL). The reaction mixture was cooled to 0 °C, Et3N (2.50
mL, 18.0 mmol) was added, and after 3 h the white precipitate
was removed by filtration. The filtrate was concentrated,
EtOAc (50 mL) was added, and the organic phase was washed
with H2O (30 mL), 1 N NaOH (30 mL), and brine (30 mL) and
dried (Na2SO4). Concentration give 2.1 g (96%) of colorless
gum; [R]20D +130.7 (c 0.84, CHCl3); IR (neat): 3278, 2958, 2140,
1717, 1653 cm-1; 1H NMR δ 7.57 (d, J ) 6.4 Hz, 2 H), 7.27 (d,
J ) 6.4 Hz, 2 H), 4.19 (d, J ) 6.8 Hz, 1 H), 3.81 (s, 3 H), 3.66
(m, 1 H), 3.13 (dd, J ) 3.2, 11.4 Hz, 1 H), 3.03 (dd, J ) 7.6,
11.4 Hz, 1 H), 2.40 (s, 3 H), 0.99 (s, 9 H); 13C NMR δ 191.8,
162.8, 143.8, 141.6, 129.9, 125.5, 62.6, 52.6, 42.3, 36.3, 26.8,
21.8 (CdN2 was not observed). HRMS calcd for C17H23N3O4S
(M + H) 366.1488, found 366.1497.
Meth yl (2S,3R,5R)-(-)-5-ter t-Bu tyl-3-h yd r oxyp yr r oli-
d in e-1-d ica r boxyla te (10). In a 50-mL, single-necked, round-
bottomed flask equipped with a magnetic stirring bar, a rubber
septum, and an argon-filled balloon was placed (-)-8 (0.074
g, 0.247 mmol) in dry MeOH (10 mL). The solution was cooled
to -78 °C, NaBH4 (0.011 g (0.297 mmol) was added, and the
mixture was stirred for 1 h. After warming to room temper-
ature the reaction was quenched with cold H2O (2 mL) and
concentrated, and H2O (5 mL) and EtOAc (15 mL) were added.
The reaction mixture was extracted with EtOAc (2 × 10 mL),
and the organic phases were dried (Na2SO4) and concentrated.
The residue was dissolved in CH2Cl2 (10 mL), TFA (0.34 mL,
4.94 mmol) was added, and the solution was stirred at room
temperature for 3 h. At this time the reaction mixture was
quenched with saturated aqueous NaHCO3 (10 mL), the
aqueous phase was extracted with EtOAc (2 × 10 mL), and
the combined organic phases were dried (Na2SO4) and con-
centrated. Chromatography (40%-60% EtOAC/hexane) af-
forded 0.07 g (94%, >96% de) of a white solid, mp 69-70 °C;
[R]20 -23.9 (c 0.83 CHCl3); IR (neat) 3132, 2955, 1747 cm-1
;
D
1H NMR δ 4.44 (m, 1 H), 3.76 (s, 3 H), 3.68 (d, J ) 3.6 Hz, 1
H), 2.83 (t, J ) 6.8 Hz, 1 H), 2.10 (m, 1 H), 2.05-2.25 (br, 2
H), 1.52 (m, 1 H), 0.936 (s, 9 H); 13C NMR δ 172.1, 73.7, 67.1,
66.8, 52.3, 36.9, 33.2, 26.9. HRMS calcd for C10H19NO3 (M +
H) 202.1443, found 202.1445.
5-ter t-Bu tyl-3-h yd r oxy-1H-p yr r ole-2-ca r boxylic Acid
Meth yl Ester (11). In a 25-mL, round-bottomed flask equipped
with magnetic stirring bar and argon balloon was placed (-)-8
(0.055 g, 0.18 mmol) in CH2Cl2 (5 mL) and anhydrous TFA (1
mL) was added. The reaction mixture was stirred at room
temperature for 3 h, at which time saturated aqueous NaHCO3
(3 mL) and H2O (1 mL) were added. The organic phase was
separated and the aqueous phase was extracted with CH2Cl2
(2 × 3 mL). The combined organic phases were dried
(Na2SO4) and concentrated.
Meth yl (R)-(-)-2-Dia zo-6,6-d im eth yl-3-oxo-N-(ter t-bu -
toxyca r bon yl)-5-a m in oh ep ta n oa te (7). In a 100-mL, one-
necked, round-bottomed flask equipped with
a magnetic
stirring bar, a rubber septum, and an argon-filled balloon was
placed 1.5 g (4.1 mmol) of (SS,R)-(+)-6 in MeOH (25 mL). The
solution was cooled to 0 °C, TFA (1.58 mL, 2.3 g, 20.5 mmol)
was added, and the reaction mixture was stirred at room
temperature for 2 h. At this time the solution was concen-
trated, the residue was dissolved in THF (20 mL), the solu-
tion was cooled to 0 °C, and Et3N (3.4 mL, 2.5 g, 24.6 mmol)
was added, followed by 4-(dimethylamino)pyridine (ca. 0.01
g). To the reaction mixture was added di-tert-butyl dicar-
bonate (0.95 g, 4.92 mmol) and the solution was stirred for 4
h at this temperature. At this time the reaction mixture was
quenched with ice and water (30 mL) and extracted with
EtOAc (2 × 30 mL). The combined organic phases were washed
with H2O (20 mL) and brine (20 mL), dried (Na2SO4), and
concentrated. Chromatography (5%-30% EtOAc/hexane) af-
1H NMR of the crude product indicated epimerization at C(2)
and a spectrum consistent with 9. Crude 9, in CH2Cl2 (2 mL),
was place in a 25-mL, round-bottomed flask equipped with
magnetic stirring bar, and 1 g of silica gel was added. After
being stirred for 5 min, at room temperature, the solvent was
concentrated, and the flask was equipped with a rubber
septum and an oxygen balloon. The solid was stirred for 4 h
at room temperature, EtOAc (6 mL) was added, and the
reaction mixture was stirred for 10 min. The solution was
filtered and concentrated. Preparative TLC (20% EtOAc/
hexane) gave 0.029 g (81%) of a white solid, mp 110-111 °C;
IR (neat) 3480, 3327, 2962, 1677 cm-1; 1H NMR (CDCl3) δ 8.15
(br, 0.5H), 7.75 (br, 1H), 6.43 (br, 0.5H), 5.66 (s, 1H), 3.85 (s,
3H), 1.28 (s, 9 H); 13C NMR (CD3OD) δ 164.4, 154.7, 149.2,
105.8, 95.3, 51.5, 33.3, 30.6; 13C NMR (CDCl3) δ 94.7, 51.2,
32.3, 30.3. HRMS calcd for C10H15NO3 197.1052, found 197.1050.
forded 1.2 g (90%) of a white solid, mp 73-74 °C; [R]20
D
-15.9 (c 0.68, CHCl3); IR (neat) 3369, 2134, 1719, 1693 cm-1
;
1H NMR δ 4.59 (d, J ) 8.4 Hz, 1 H), 3.90 (m, 1 H), 3.85 (s, 3
H), 3.24 (dd, J ) 2.4, 10.6 Hz, 1 H), 2.64 (t, J ) 9.2 Hz, 1 H),
1.40 (s, 9 H), 0.95 (s, 9 H); 13C NMR δ 192.1, 162.4, 156.2,
79.5, 56.7, 52.7, 42.0, 35.3, 28.7, 26.7 (CdN2 was not observed).
(R)-(+)-5-ter t-Bu tyl-3-(d ieth oxyp h osp h or yloxy)-4,5-d i-
h yd r op yr r ole-1,2-d ica r b oxy Acid 1-ter t-Bu t yl E st er 2-
Meth yl Ester (12). In a 100-mL, one-necked, round-bottomed
flask equipped with a magnetic stirring bar and an argon-filled
balloon were placed (-)-8 (0.45 g, 1.5 mmol) and 18-crown-6
(1.05 g, 4.0 mmol) in THF (20 mL). The solution was cooled to
HRMS calcd for
350.1693.
C15H25N3O5 (M + Na) 350.1692, found
5150 J . Org. Chem., Vol. 68, No. 13, 2003