PAPER
Pyrrolam A
1501
tiomer (1R,7aS)-6: [a]D –91.5 (c = 1, CHCl3); Lit.22 for diastereo-
mer (1S,7aS)-6: [a]D –48.8 (c = 0.3, CHCl3)}.
IR (ATR): 3347, 1657, 1421, 1080 cm–1.
yield: 0.35 g (65%); colorless solid; mp 67 °C; Rf = 0.43 (EtOAc);
[a]D25 +26.1 (c = 0.9, CHCl3).
IR (ATR): 1667, 1615, 1343 cm–1.
1H NMR (CDCl3): d = 1.42 (ddt, J = 11.9, 9.1, 8.4 Hz, 1 H, 7-H),
1.90–2.07 (m, 2 H, 6-H), 2.11 (m, 1 H, 7-H), 2.71 (d, J = 8.4 Hz, 2
H, 2-H), 2.95 (ddd, J = 11.6, 8.2, 4.5 Hz, 1 H, 5-H), 3.48 (dt,
J = 11.6, 7.8 Hz, 1 H, 5-H), 3.73 (ddd, J = 9.1, 6.1, 6.0 Hz, 1 H, 7a-
H), 4.18 (dt, J = 8.4, 6.0 Hz, 1 H, 1-H), 4.69 (br s, 1 H, OH).
13C NMR (75.5 MHz, CDCl3): d = 26.5 (C6), 29.7 (C7), 41.5 (C5),
44.3 (C2), 69.4 (C7a), 73.0 (C1), 172.8 (C3).
1H NMR (CDCl3): d = 1.10 (ddt, J = 12.8, 11.8, 3.4 Hz, 1 H, 8-H),
1.18–1.48 (m, 2 H, 6-H, 7-H), 1.58–1.67 (m, 1 H, 6-H), 1.80–1.90
(m, 1 H, 7-H), 2.06–2.16 (m, 1 H, 8-H), 2.70 (dt, J = 12.8, 3.5 Hz,
1 H, 5-H), 3.75 (dd, J = 11.8, 4.1 Hz, 1 H, 8a-H), 4.18–4.26 (m, 1
H, 5-H), 4.91 (d, J = 11.8 Hz, 1 H, OCH), 4.95 (d, J = 11.8 Hz, 1 H,
OCH), 5.05 (s, 1 H, 2-H), 7.26–7.40 (m, 5 Harom).
13C NMR (75.5 MHz, CDCl3): d = 23.0 (C7), 25.5 (C6), 29.7 (C8),
38.2 (C5), 58.6 (C8a), 72.6 (OCH2), 94.3 (C2), 127.6, 128.1, 128.2,
128.5, 128.6 (ar-CH), 135.0 (ar-Cq), 169.3 (C1), 175.3 (C3).
MS: m/z (%) = 141 (49, [M+]), 113 (19), 112 (66), 70 (100).
HRMS (EI): m/z calcd for C7H11NO2: 141.07898; found:
141.07890.
MS: m/z (%) = 243 (13, [M+]), 222 (2), 154 (4), 91 (100).
HRMS (EI): m/z calcd for C15H17NO2: 243.12593; found:
(1S,7aR)-1-Mesyloxypyrrolizidin-3-one (7)
243.12590.
To a solution of (1S,7aR)-6 (185 mg, 1.32 mmol) in CH2Cl2 (10 mL)
at 0 °C were added first mesyl chloride (212 mg, 143 mL, 1.85
mmol), and then Et3N (187 mg, 257 mL, 1.85 mmol). The mixture
was stirred at 0 °C for 2 h, and then for another 16 h at r.t. H2O (15
mL) was added and the resulting mixture was extracted with CH2Cl2
(3 × 30 mL). The combined organic extracts were dried (Na2SO4),
filtered and evaporated to dryness. The remainder was purified by
column chromatography (silica gel; CHCl3–MeOH, 12:1 + 0.5%
Et3N). Flakey sallow crystals (245 mg, 90%) from EtOAc–MeOH
(R)-Indolizidine-1,3-dione [(R)-10]
Crude (R)-10 (175 mg, 99%) was obtained as a yellow oil from (R)-
9 (280 mg, 1.15 mmol) by the procedure described for compound
(R)-5; Rf = 0.52 (CH2Cl2–MeOH, 19:1).
1H NMR (CDCl3): d = 1.12–1.51 (m, 3 H, 6-H, 7-H, 8-H), 1.64–
1.73 (m, 1 H, 6-H), 1.88–2.08 (m, 2 H, 7-H, 8-H), 2.61–2.73 (m, 1
H, 5-H), 2.90 (ddd, J = 22.1, 1.6, 0.9 Hz, 1 H, 2-H), 3.00 (ddd,
J = 22.1, 2.0, 0.9 Hz, 1 H, 2-H), 3.70 (ddt, J = 11.9, 3.9, 0.9 Hz, 1
H, 8a-H), 4.35 (m, 1 H, 5-H).
13C NMR (75.5 MHz, CDCl3): d = 23.0 (C7), 24.1 (C6), 27.0 (C8),
38.9 (C5), 40.7 (C2), 64.7 (C8a), 166.6 (C3), 206.1 (C1).
MS: m/z (%) = 153 (22, [M+]), 152 (3), 125 (99), 97 (100).
(3:1); mp 82 °C {Lit.4 for enantiomer (1R,7aS)-7: mp 82 °C; [a]D
25
46 (c = 1.3, CHCl3); Lit.4 for enantiomer (1R,7aS)-7: [a]D –56.9
(c = 1, CHCl3)}.
IR (ATR): 1684, 1348, 1335, 1166, 1002 cm–1.
1H NMR (CDCl3): d = 1.47 (ddt, J = 12.4, 9.4, 8.8 Hz, 1 H, 7-H),
1.89–2.11 (m, 2 H, 6-H), 2.09–2.20 (m, 1 H, 7-H), 2.84–3.00 (m, 2
H, 2-H), 3.01 (s, 3 H, CH3), 3.03–3.11 (m, 1 H, 5-H), 3.54 (dt,
J = 11.9, 7.9 Hz, 1 H, 5-H), 3.95 (ddd, J = 9.4, 6.2, 5.3 Hz, 1 H, 7a-
H), 4.92 (dt, J = 8.3, 5.3 Hz, 1 H, 1-H).
(1S,8aR)-1-Hydroxyindolizidin-3-one (11)
A solution of crude (R)-10 (175 mg, 1.15 mmol) in CH2Cl2 (3 mL)
was added over a period of 30 min to a solution of (R)-2-methylox-
azaborolidineborane (12; 334 mg, 1.15 mmol) in CH2Cl2 (2 mL)
kept at –20 °C. After stirring for 2 h at this temperature, the reaction
was quenched with MeOH (10 mL) and stirring was continued for
another hour. All volatiles were removed in vacuo, and the residue
was purified by preparative TLC (silica gel; CH2Cl2–MeOH, 9:1;
Rf = 0.49) to give 74 mg (42%) of (1S,8aR)-11 as a viscous oil;
13C NMR (75.5 MHz, CDCl3): d = 26.2 (C6), 29.8 (C7), 38.5 (CH3),
41.4 (C2), 41.9 (C5), 67.1 (C7a), 77.9 (C1), 170.3 (C3).
MS: m/z (%) = 140 (24), 124 (6), 123 (56), 70 (100).
(–)-Pyrrolam A (1)
25
dr = 95:5 (chiral GC, NMR); [a]D –9 (c = 1, acetone) {Lit.23
A mixture of (1S,7aR)-7 (245 mg, 1.16 mmol), CH2Cl2 (20 mL), and
Et3N (1.20 mL) was heated at reflux for 18 h. The solvent was re-
moved and the residue purified by preparative TLC (silica gel;
CHCl3–MeOH, 12:1 + 0.5% Et3N); Rf = 0.59 (acetone–toluene, 2:1;
detection by staining with Ehrlich’s reagent); colorless solid (92
mg, 65%); mp 58 °C [Lit.5mp 59 °C; Lit.6mp 61.5 °C; Lit.7mp 56–
for enantiomer (1R,8aS)-11: [a]D +11 (c = 1, acetone)}.
IR (ATR): 3380, 1666 cm–1.
1H NMR (CDCl3): d = 1.10 (ddt, J = 12.7, 12.1, 3.6 Hz, 1 H, 8-H),
1.20–1.46 (m, 2 H, 6-H, 7-H), 1.60–2.19 (m, 3 H, 6-H, 7-H, 8-H),
2.35 (ddd, J = 17.4, 5.1, 1.8 Hz, 1 H, 2-H), 2.57–2.74 (m, 2 H, 2-H,
5-H), 3.28 (dt, J = 11.9, 3.6 Hz, 1 H, 8a-H), 3.35 (br s, 1 H, OH),
4.02–4.15 (m, 2 H, 1-H, 5-H).
13C NMR (75.5 MHz, CDCl3): d = 23.4 (C7), 24.4 (C6), 30.4 (C8),
40.2 (C5), 40.3 (C2), 65.7 (C8a), 70.6 (C1), 171.3 (C3).
25
58 °C]; [a]D –25.2 (c = 1.24, CHCl3) {Lit.5,6[a]D –26.3 (c = 0.8,
CHCl3)}; 95% ee by chiral GC.
IR (ATR): 1670, 810 cm–1.
1H NMR (CDCl3): d = 1.11 (ddt, J = 11.8, 10.8, 7.7 Hz, 1 H, 7-H),
2.03 (ddt, J = 11.8, 6.0, 1.7 Hz, 1 H, 7-H), 2.13–2.35 (m, 2 H, 6-H),
3.21 (ddd, J = 11.4, 8.5, 5.8 Hz, 1 H, 5-H), 3.35–3.46 (m, 1 H, 5-H),
4.16–4.24 (m, 1 H, 7a-H), 5.96 (dd, J = 5.8, 1.6 Hz, 1 H, 2-H), 7.15
(dd, J = 5.8, 1.8 Hz, 1 H, 1-H).
MS: m/z (%) = 155 (62, [M+]), 126 (58), 120 (43), 83 (100).
HRMS (EI): m/z calcd for C8H14NO3: 155.09463; found:
155.09460.
13C NMR (75.5 MHz, CDCl3): d = 28.9 (C7), 29.8 (C6), 41.8 (C5),
(1S,8aS)-1-Hydroxyindolizidin-3-one (11)
67.7 (C7a), 128.3 (C2), 148.8 (C1), 175.4 (C3).
A 1:1 mixture of (1S,8aR)-11 and (1S,8aS)-11 was obtained from
( )-10 (95 mg) and 12 (180 mg) as described above for the synthesis
of pure (1S,8aR)-11 from (R)-10. After removal of by-product
diphenylprolinol by preparative TLC, the mixture (39 mg, 40%)
was dissolved in a minimum amount of EtOAc. Upon standing in
the refrigerator, 15 mg of colorless crystalline (1S,8aS)-11 precipi-
MS: m/z (%) = 123 (94, [M+]), 119 (32), 106 (32), 105 (23), 104
(26), 95 (68), 67 (100).
HRMS (EI): m/z calcd for C7H9NO: 123.06841; found: 123.06840.
(R)-1-Benzyloxyindolizidin-1-en-3-one [(R)-9]
tated; mp 156–158 °C [Lit.24 mp 149–157 °C]; [a]D +23.9
25
Prepared from (R)-814 (0.48 g, 2.19 mmol) and PS-3 (2.20 g, 2.85
mmol) according to the procedure described for compound (R)-4;
(c = 0.5, acetone) {Lit.24 [a]D +26.9 (c = 1.5, acetone)}.
Synthesis 2007, No. 10, 1499–1502 © Thieme Stuttgart · New York