Enantioselective Total Synthesis of Tripterygium Compounds
J . Org. Chem., Vol. 65, No. 7, 2000 2215
dropwise. After 10 min, n-butyllithium (1.60 M, 0.69 mL, 1.10
mmol) was added to the mixture slowly. The solution was
stirred at -10 °C for 30 min. A solution of allylic bromide 14
(327 mg, 1.05 mmol) in THF (5 mL) was transferred into the
above mixture via a cannula, and the reaction was stirred at
-10 °C for another 1.5 h. Saturated ammonium chloride
solution was added to quench the reaction. The resulting
mixture was extracted with dichloromethane. The extracts
were dried with anhydrous sodium sulfate, filtered, and
concentrated. The residue was purified by flash column
chromatography to afford compound 17a (504 mg, 0.87 mmol,
found 544.3553; LRMS (EI, 70 eV) m/z 544 (M+, 17), 426 (42),
214 (26), 119 (100). Anal. Calcd for C36H48O4: C, 79.37; H, 8.88.
Found: C, 79.37; H, 9.22.
Mn (III)-Ba sed Oxid a tive F r ee-Ra d ica l Cycliza tion of
17a . To a solution of acyclic precursor 17a (116 mg, 0.20 mmol)
in degassed CH3OH (2 mL) was added Mn(OAc)3‚2H2O (118
mg, 0.44 mmol) in one portion at 0 °C. The reaction was stirred
at 0 °C for 14 h. Saturated NaHSO3 solution was added to the
mixture followed by extraction with CH2Cl2. The extracts were
dried with anhydrous Na2SO4, filtered, concentrated, and
purified by flash column chromatography to afford trans-ring
junction products 24 (99 mg, 0.17 mmol, 85% yield) as a white
solid. Diastereomers 24 were separated by preparative HPLC
(Chiralcel OD column, eluting solvent 1% i-PrOH in n-hexane,
flow rate 5 mL/min) to afford D and E as major compounds
(E was more abundant than D).
87% yield) as colorless oil. [R]20 ) +12.4° (c 1.22, CH2Cl2);
D
analytical TLC (silica gel 60), 10% EtOAc in n-hexane, Rf )
0.44; 1H NMR (300 MHz, CDCl3) δ 12.48 (s, 0.36 × 1H, enol),
6.32-6.98 (m, 8H), 5.32-5.16 (m, 1H), 4.94-4.84 (m, 1H), 4.07
(s, 0.21 × 1H, ketone 1), 3.71 (s, 0.36 × 3H, enol), 3.70 (s, 0.64
× 3H, ketones 1 & 2), 3.54 (s, 0.42 × 1H, ketone 2), 3.32 (sept,
J ) 6.9 Hz, 1H), 2.73-0.82 (m, 34H); 13C NMR (75 MHz,
CDCl3) δ 199.4 (ketone 1), 198.1, (ketone 2), 174.9, 168.5, 165.0,
163.6, 155.5, 151.9, 150.8, 150.0, 141.6, 134.7, 133.8, 133.3,
128.0, 127.9, 127.4, 125.5, 125.4, 125.3, 125.2, 125.1, 125.0,
124.3, 124.1, 97.0, 77.5, 76.7, 76.3, 61.5, 60.5, 59.8, 50.4, 50.3,
50.0, 41.6, 40.9, 40.8, 40.0, 39.6, 39.2, 37.9, 37.8, 35.3, 34.3,
33.0, 31.9, 31.5, 31.3, 31.2, 31.1, 30.1, 29.8, 29.1, 29.0, 27.2,
27.0, 26.6, 26.3, 26.0, 25.8, 23.9, 22.6, 22.1, 21.6, 15.8, 15.7;
IR (CH2Cl2) 1754, 1727 cm-1; HRMS (EI) calcd for C36H49ClO4
(M+): 580.3319; found 580.3314; LRMS (EI, 70 eV) m/z 580
(M+, 1), 119 (91), 105 (100). Anal. Calcd for C36H49ClO4: C,
74.39; H, 8.50. Found: C, 74.65; H, 8.81.
D: White solid, mp 201-202 °C (CH2Cl2); [R]20 ) -54.8°
D
(c 0.42, CH2Cl2); analytical TLC (silica gel 60), 20% EtOAc in
1
n-hexane, Rf ) 0.48; H NMR (300 MHz, CDCl3) δ 7.52-7.13
(m, 5H), 7.09 (d, J ) 8.3 Hz, 1H), 7.00 (d, J ) 8.3 Hz, 1H),
4.92 (dt, J ) 4.4, 10.7 Hz, 1H), 3.72 (s, 3H), 3.30 (sept, J ) 6.9
Hz, 1H), 3.16 (m, 1H), 3.04 (dt, J ) 5.8, 13.7 Hz, 1H), 2.83
(dq, J ) 2.5, 14.4 Hz, 1H), 2.75-2.28 (m, 4H), 2.11-1.70 (m,
3H), 1.53-1.42 (m, 2H), 1.39 (s, 3H), 1.32 (s, 3H), 1.32-1.20
(m, 4H), 1.27 (s, 3H), 1.22 (d, J ) 6.9 Hz, 3H), 1.20 (d, J ) 6.9
Hz, 3H), 1.10 (m, 1H), 0.93 (m, 1H), 0.85 (d, J ) 6.2 Hz, 1H),
0.72 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 198.1, 165.9, 155.1,
149.7, 144.1, 139.2, 128.6, 128.0, 125.9, 125.4, 124.3, 121.1,
78.3, 78.0, 60.6, 56.6, 50.7, 40.9, 40.4, 39.7, 39.2, 37.7, 34.1,
31.7, 31.3, 30.9, 27.5, 26.1, 23.9, 23.8, 23.8, 22.5, 21.7, 21.3;
IR (CH2Cl2) 1749, 1731 cm-1; HRMS (EI) calcd for C36H47ClO4
(M+): 578.3163, found 578.3155; LRMS (EI, 20 eV) m/z 578
(M+, 4), 214 (17), 119 (100).
Mn (III)-Ba sed Oxid a tive F r ee-Ra d ica l Cycliza tion of
17 in th e Absen ce of Lew is Acid s. To a solution of acyclic
precursor 17 (163.8 mg, 0.30 mmol) in acetic acid (3 mL) was
added Mn(OAc)3‚2H2O (182.3 mg, 0.66 mmol) under argon. The
mixture was stirred at 50 °C. The color of the mixture turned
to white after 1 h. Saturated NaHSO3 solution was added to
the mixture followed by extraction with CH2Cl2. The extract
was dried with anhydrous Na2SO4, concentrated, and purified
by flash column chromatography (5% to 10% EtOAc in n-
hexane) to afford trans-ring junction products 20 and 21 (68.6
mg, 42% yield) and cis-ring junction products 22 and 23 (13.1
E: White solid, mp 86-89 °C (Et2O/n-hexane); [R]20
)
D
+51.2° (c 0.09, CH2Cl2); analytical TLC (silica gel 60), 20%
1
EtOAc in n-hexane, Rf ) 0.48; H NMR (300 MHz, CDCl3) δ
7.36-7.15 (m, 5H), 7.09 (d, J ) 8.3 Hz, 1H), 7.01 (d, J ) 8.3
Hz, 1H), 4.88 (dt, J ) 4.2, 10.6 Hz, 1H), 3.73 (s, 3H), 3.30 (sept,
J ) 6.9 Hz, 1H), 3.17 (m, 1H), 3.08 (dt, J ) 6.1, 15.0 Hz, 1H),
2.78 (dq, J ) 2.4, 14.9 Hz, 1H), 2.72-2.46 (m, 3H), 2.25-2.08
(m, 4H), 1.93 (dt, J ) 3.6, 14.3 Hz, 1H), 1.84 (dt, J ) 4.2, 14.8
Hz, 1H), 1.47 (s, 3H), 1.41 (s, 3H), 1.30 (s, 3H), 1.27 (m, 1H),
1.21 (d, J ) 6.9 Hz, 3H), 1.20 (d, J ) 6.9 Hz, 3H), 1.08-0.85
(m, 3H), 0.82 (d, J ) 6.4 Hz, 3H), 0.74 (m, 1H); 13C NMR (67.5
MHz, CDCl3) δ 198.5, 167.7, 154.9, 149.9, 144.2, 139.2, 128.5,
128.1, 125.8, 125.5, 124.4, 121.1, 79.6, 78.5, 60.5, 55.9, 50.4,
41.1, 40.3, 39.6, 38.7, 37.6, 34.2, 31.5, 31.4, 31.0, 30.9, 27.7,
26.1, 26.0, 23.9, 23.7, 23.6, 21.8, 21.7; IR (CH2Cl2) 1741, 1707
cm-1; HRMS (EI) calcd for C36H47ClO4 (M+): 578.3163, found
578.3168; LRMS (EI, 20 eV) m/z 578 (M+, 2), 119 (100).
Mn (III)-Ba sed Oxid a tive Ra d ica l Cycliza tion of 17 in
th e P r esen ce of Lew is Acid s. To a solution of acyclic
precursor 17 (54.6 mg, 0.10 mmol) in degassed CF3CH2OH (1
mL) was added Yb(OTf)3‚H2O (62.0 mg, 0.10 mmol) under
argon atmosphere. The mixture was stirred at room temper-
ature for 10 min and then cooled to -5 °C. Mn(OAc)3‚2H2O
(60.8 mg, 0.22 mmol) was added in one portion. The reaction
was monitored by TLC. Saturated NaHSO3 solution was added
to the mixture followed by extraction with CH2Cl2. The extracts
were dried with anhydrous Na2SO4, filtered, concentrated, and
purified by flash column chromatography (5% to 10% EtOAc
in n-hexane) to afford trans-ring junction products 20 and 21
(41.9 mg, 77% yield) and trace amount of cis-ring junction
products 22 and 23.
1
mg, 8% yield). The ratio of 20:21 was determined by H NMR
(500 MHz, CDCl3) analysis. Diastereomers 20 and 21 were
separated by preparative HPLC (silica gel column, eluting
solvent 4% i-PrOH in n-hexane, flow rate 8 mL/min).
20: white solid, mp 84-86 °C (MeOH); analytical TLC
(silica gel 60), 20% EtOAc in n-hexane, Rf ) 0.47; [R]20
)
D
1
-49.8° (c 0.11, CH2Cl2); H NMR (300 MHz, CDCl3) δ 7.29-
7.02 (m, 7H), 4.77 (dt, J ) 3.9, 10.6 Hz, 1H), 3.67 (s, 3H), 3.27
(sept, J ) 6.9 Hz, 1H), 2.93 (apparent dd, J ) 4.0, 17.6 Hz,
1H), 2.69-2.63 (ddd, J ) 8.0, 10.7, 18.5 Hz, 1H), 2.51 (m, 3H),
2.30-2.15 (m, 3H), 2.05 (m, 1H), 1.83 (m, 1H) 1.75-1.45 (m,
6H), 1.35 (s, 3H), 1.24 (s, 3H), 1.23 (d, J ) 6.9 Hz, 3H), 1.20
(d, J ) 6.9 Hz, 3H), 1.18 (s, 3H), 0.90 (d, J ) 6.5 Hz, 3H),
1.15-0.83 (m, 1H); 13C NMR (67.5 MHz, CDCl3) δ 205.1, 169.3,
155.0, 152.0, 143.8, 139.0, 128.4, 127.5, 125.8, 124.6, 124.0,
120.9, 60.4, 59.4, 50.4, 44.8, 41.3, 39.6, 38.0, 37.1, 36.1, 34.7,
31.3, 30.9, 27.3, 26.6, 26.0, 25.0, 23.9, 23.8, 23.8, 23.1, 22.0,
21.8; IR (CH2Cl2) 1733, 1730 cm-1; HRMS (EI) calcd for
C
36H48O4 (M+): 544.3552, found 544.3564; LRMS (EI, 20 eV)
m/z 544 (M+, 21), 426 (100), 214 (50), 119 (63). Anal. Calcd for
C
36H48O4: C, 79.37; H, 8.88. Found: C, 79.37; H, 9.01.
21: white solid, mp 91-93 °C (EtOAc/n-hexane); analytical
TLC (silica gel 60), 20% EtOAc in n-hexane, Rf ) 0.47; [R]20
D
) +60.8° (c 0.074, CH2Cl2); 1H NMR (300 MHz, CDCl3) δ 7.25
(m, 4H), 7.05 (m, 3H), 4.81 (dt, J ) 4.0, 10.7 Hz, 1H), 3.72 (s,
3H), 3.30 (sept, J ) 6.9 Hz, 1H), 3.03 (apparent dd, J ) 4.0,
17.6 Hz, 1H), 2.75 (m, 1H), 2.65 (d, J ) 13.1 Hz, 1H), 2.60-
2.30 (m, 3H), 2.30-2.07 (m, 2H), 1.84-1.35 (m, 7H), 1.31 (s,
3H), 1.25 (s, 3H), 1.24 (d, J ) 6.9 Hz, 3H), 1.22 (d, J ) 6.9 Hz,
3H), 1.21 (s, 3H), 1.15-0.83 (m, 3H), 0.92 (d, J ) 6.5 Hz, 3H);
13C NMR (125 MHz, CDCl3) δ 205.6, 168.8, 155.2, 152.1, 144.1,
139.0, 128.6, 127.9, 125.5, 124.7, 124.0, 120.8, 76.0, 60.5, 59.2,
44.0, 41.1, 39.6, 38.1, 37.5, 36.2, 34.8, 31.4, 28.3, 26.6, 26.2,
24.6, 24.2, 24.0, 24.0, 23.8, 23.6, 22.4, 21.8; IR (CH2Cl2) 1732,
1703 cm-1; HRMS (EI) calcd for C36H48O4 (M+): 544.3553,
P r ep a r a tion of Com p ou n d 30. The procedure for the
preparation of 17 was followed. Compound 30: colorless oil;
analytical TLC (silica gel 60), 20% EtOAc in n-hexane, Rf )
0.57; [R]20 ) -14.2° (c 1.05, CH2Cl2); HRMS (EI) calcd for
D
C
36H50O4 (M+): 546.3709, found 546.3705; LRMS (EI, 20 eV)
m/z 546 (M+, 12), 163 (42), 119 (100), 105 (94). Anal. Calcd for
36H50O4: C, 79.08; H, 9.22. Found: C, 79.20; H, 9.50. For
C
other characterization data, see those of 17.
P r ep a r a tion of Com p ou n d 31. The procedure for the
preparation of 20 in the presence of Yb(OTf)3 was followed.
Compound 31: white solid, mp 87-89 °C (EtOH/n-hexane);