recovered starting material. Two isomers of the product were obtained in a 2:1 ratio. Isomer 1: 1H NMR
(CDCl3/300 MHz) (two main rotamers with approximately 9:1 ratio observed) δ 7.33-7.24 (m, 5H), 5.46
(d, J=3.9Hz, 0.1H), 5.33 (d, J=8.7Hz, 0.9H), 4.77-4.70 (m, 1H), 4.53 (d, J=9.3Hz, 1H), 4.43 (d, J=3.9Hz,
1H), 3.75 and 3.72 (s and s, 3H), 3.39 and 3.23 (s and s, 3H), 3.10-2.94 (m, 2H), 2.32-2.20 (m 1H), 1.92-
1.86 (m, 2H), 1.79-1.60 (m, 1H), 1.39 (s, 9H); 13C NMR (CDCl3/75 MHz) δ 172.1, 172.0, 154.9, 136.9,
129.9, 129.7, 128.6, 127.0, 88.8, 79.6, 58.7, 55.1, 53.9, 52.4, 40.8, 29.7, 29.5, 28.5, 25.9; IR (neat/NaCl)
3314, 1742, 1651, 1520, 1249, 1169, 853 cm-1; LRFAB MS (relative intensity) m/z 413 (100) MLi+, 397
(6), 395 (57) MLi+-H2O, 313 (61) MLi+-Boc+H, 289 (20); HRFAB MS m/z calculated for [M+Li]+
1
413.2264, found 413.2246. Isomer 2: H NMR (CDCl3/300 MHz) (two main rotamers with
approximately 2:1 ratio observed) δ 7.32-7.20 (m, 5H), 5.48 (d, J=4.8Hz, 0.67H), 5.39 (d, J=5.1Hz,
0.33H), 5.01 (d, J=9.3Hz, 1H), 4.73 (td, J=9.0, 3.9Hz, 1H), 4.46-4.40 (m, 1H), 3.75and 3.71 (s and s, 3H),
3.36 and 3.33 (s and s, 3H), 3.49-3.26 (m, 1H), 2.86-2.79 (m, 1H), 2.32-1.90 (m, 4H), 1.45, 1.42 and 1.34
(s, s and s, 9H); 13C NMR (CDCl3/75 MHz) δ 172.9, 172.1, 172.0, 137.1, 129.6, 128.8, 128.5, 128.4,
127.3, 89.2, 87.7, 79.9, 59.4, 58.2, 56.2, 54.1, 53.6, 53.3, 52.9, 52.4, 41.4, 39.0, 31.1, 30.6, 28.5, 28.4,
27.2, 26.5, 26.1; IR (neat/NaCl) 3314, 1742, 1651, 1520, 1249, 1169, 853 cm-1; LRFAB MS (relative
intensity) m/z 413 (100) MLi+, 397 (6), 395 (57) MLi+-H2O, 313 (61) MLi+-Boc+H, 289 (20); HRFAB
MS m/z calculated for [M+Li]+ 413.2264, found 413.2246.
2-Benzyl-3-oxo-hexahydropyrrolo[1,2-a]imidazole-5-carboxylic acid methyl ester (23):
To an oven-dried 50 mL round bottom flask was added the methoxylated dipeptide substrate (175
o
.
mg, 0.43 mmol) and anhydrous ether (15 mL) at -78 C. BF3 Et2O (54.5 μl, 0.43 mmol) was added and
the reaction mixture was allowed to stir at -78 oC for 1 hour. The solution was then allowed to warm to
room temperature over a period of 30 min. The reaction was quenched with sat. sodium bicarbonate
solution and transferred to a separatory funnel. The layers were separated and the aqueous layer extracted
with ether. The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude
product was chromatographed through silica gel using a gradient elution from 1:1 EtOAc/hexane to 5%
1
methanol/EtOAc. The column afforded 88 mg (75%) of the desired cyclized product. H NMR
(CDCl3/300 MHz) δ 7.30-7.16 (m, 5H), 4.94 (dd, J=7.4, 5.0Hz, 1H), 4.42 (dd, J=9.2, 6.2Hz, 1H), 4.16
(dd, J=8.3, 3.8Hz, 1H), 3.72 (s, 3H), 3.14 (dd, J=13.8, 3.6Hz, 1H), 2.76 (dd, J=13.8, 8.7Hz, 1H), 2.34-
13
2.23 (m, 2H), 2.03-1.90 (m, 2H), 1.14-1.05 (m, 1H); C NMR (CDCl3/75 MHz) δ 174.9, 172.2, 138.3,
129.7, 128.5, 126.6, 76.0, 63.9, 55.1, 52.6, 39.0, 33.3, 29.8; IR (neat/NaCl) 3353, 2951, 1744, 1707, 1401,
1200, 1178 cm-1; LRFAB MS (relative intensity) m/z 275 (14) MH+, 154 (100); HRFAB MS m/z
calculated for [M+H]+ 275.1396, found 275.1392. The stereochemistry was assigned using an NOE
crosspeak between the proton on the bridge-head carbon and the proton on the carbon next to the benzyl.
1-(2-tert-Butoxycarbonylamino-3-hydroxypropionyl)-5-methoxypyrrolidine-2-carboxylic
methyl ester:
acid
The silylated dipeptide substrate (202 mg, 0.45 mmol) was oxidized using the general procedure
outlined above. In this experiment, 2.2 F/mol of current was passed through the electrolysis cell. The
crude product was chromatographed through silica gel using a gradient elution from 1:1.5 EtOAc/hexane
to 10% mehthanol/EtOAc. The column afforded 118 mg (76%) of the desired product as a mixture of
two isomers (1:1 ratio). Isomer 1: 1H NMR (CDCl3/300 MHz) δ 5.51 (br s, 1H), 5.26 (dd, J=5.0, 4.0Hz,
1H), 4.76 (dd, J=7.4, 5.2Hz, 1H), 4.48-4.37 (m, 2H), 3.75 (s, 3H), 3.69 (dd, J=10.0, 6.4Hz, 1H), 3.48 (s,
3H), 2.35-2.29 (m, 2H), 2.02-1.95 (m, 2H), 1.45 (s, 9H); 13C NMR (CDCl3/75 MHz) δ 171.9, 171.6,
171.3, 166.8, 155.9, 89.1, 88.0, 87.5, 80.3, 69.3, 68.8, 64.0, 59.2, 59.0, 58.8, 58.2, 57.9, 54.7, 52.9, 52.7,
52.5, 49.2, 31.9, 31.6, 31.2, 30.9, 30.2, 28.9, 28.4, 27.8, 26.5, 26.3, 26.2, 26.0; IR (neat/NaCl) 3432, 2978,
1747, 1714, 1667, 1435, 1170, 1086, 859 cm-1; LRFAB MS (relative intensity) m/z 353 (100) MLi+, 253
(20) MLi+-Boc+H, 134 (53); HRFAB MS m/z calculated for [M+Li]+ 353.1919, found 353.1923. Isomer
2: 1H NMR (CDCl3/300 MHz) δ 5.49 (d, J=4.2Hz, 1H), 5.38 (d, J=7.5Hz, 1H), 4.83 (br d, J=6.6Hz, 1H),
4.69 (d, J=9.3Hz, 1H), 3.89 (dd, J=11.1, 5.4Hz, 1H), 3.76 (s, 3H), 3.63 (dd, J=11.1, 8.1Hz, 1H), 3.38 (s,
S9