5092 J . Org. Chem., Vol. 63, No. 15, 1998
Kohrt et al.
diethyl ether (3 mL). The solution was dried over MgSO4,
filtered, and concentrated under reduced pressure. Purifica-
tion of the resulting oil by flash chromatography (1:1 petroleum
ether/EtOAc) gave diol 8 (19 mg, 96%) as a clear oil: IR (neat)
3393, 3034, 2921, 2851, 1718, 1365, 1243, 1076, 1013, 949, 879,
Et3N (17.5 µL, 0.126 mmol) in CH2Cl2 (1 mL) was cooled to 5
°C and methanesulfonyl chloride (7.0 µL, 0.093 mmol) was
added. The reaction mixture was then allowed to warm to rt
over 3 h, concentrated under reduced pressure onto Na2SO4,
and filtered through a plug of silica gel (petroleum ether/
EtOAc, 4:1). The resulting crude oil was dissolved in methanol
(1 mL) and NaOMe (13 mg, 0.231 mmol) was added; the
reaction mixture was stirred for 12 h. H2O (2 mL) was added
and the aqueous solution was extracted with diethyl ether (3
× 3 mL). The combined diethyl ether extracts were dried over
MgSO4 and concentrated under reduced pressure. The result-
ing crude oil was purified by flash chromatography (petroleum
ether/EtOAc, 20:1-10:1) to give aziridine 10c (23 mg, 62%)
as an amber oil: IR (neat) 3048, 2954, 2928, 2856, 1597, 1467,
1359, 1331, 1254, 1161, 1091, 965, 866, 837, 778 cm-1; 1H NMR
(300 MHz, CDCl3) δ 0.03 (s, 3H), 0.58 (s, 3H), 0.81 (s, 9H),
2.44 (s, 3H), 3.34 (dd, 1H, J ) 3.6, 6.6 Hz), 3.63 (dddd, 1H, J
) 2.0, 2.0, 2.0, 7.0 MHz), 4.01 (dd, 1H, J ) 2.3, 4.6 Hz), 4.41
(dd, 1H, J ) 4.3, 4.3 Hz), 5.86 (dd, 1H, J ) 4.3, 9.6 Hz), 6.06
(dd, 1H, J ) 5.0, 9.0 Hz), 7.32 (d, 2H, J ) 7.9 Hz), 7.82 (d, 2H,
J ) 8.6 Hz); 13C NMR (75 MHz, CDCl3) δ -4.8, -4.4, 17.9,
21.6, 25.6, 35.7, 44.9, 46.9, 69.4, 76.5, 123.7, 127.8, 129.7, 134.0,
144.6; MS (CI) m/e 458 (M+), 402 (M - C4H9)+, 378 (M - Br)+,
321, 287, 155, 115, 91; HRMS (EI) calcd for C15H19BrNO3SiS
(M - C4H9)+ 400.0038, found 400.0025.
696 cm-1 1H NMR (300 MHz, CDCl3) δ 2.10 (s, 3H), 2.42
;
(broad s, 1H), 2.69 (broad s, 1H), 4.11 (m, 1H), 4.31 (dd, 1H, J
) 2.6, 6.3 Hz), 4.58 (m, 1H), 5.33 (dd, 1H, J ) 4.3, 4.3 Hz),
5.78 (dd, 1H, J ) 3.0, 13.9 Hz), 5.96 (dd, 1H, J ) 3.0, 10 Hz);
13C NMR (75 MHz, CDCl3) δ 21.0, 58.5, 69.9, 70.9, 71.2, 125.3,
131.2, 184.5; MS (EI) m/e 190 (M - HC2O2)+, 128, 111, 86, 43;
HRMS (EI) calcd for C6H7BrO2 (M - HC2O2)+ 189.9629, found
189.9632.
r el-(1R,4S,5S,6R)-4-Ben zyloxy-7-oxa bicyclo[4.1.0]h ep t-
2-en -5-ol (9). To a 0 °C solution of alcohol 6a (90 mg, 0.218
mmol) in THF (2 mL) was added TBAF (1.0 M, 436 µL, 0.436
mmol). The reaction mixture was allowed to warm to rt and
was stirred a total of 4 h before being quenched with saturated
aqueous NH4Cl (4 mL). The aqueous solution was extracted
with diethyl ether (2 × 4 mL), and the combined organic layers
were washed with brine and dried over Na2SO4. Concentration
of the organic solution and purification of the resulting oil by
flash chromatography (3:1 hexanes/EtOAc) gave epoxide 9 (40
mg, 85%) as a clear oil: IR (neat) 3440, 3030, 2867, 1643, 1496,
1454, 1391, 1250, 1070, 994, 810, 787, 740, 692 cm-1; 1H NMR
(500 MHz, CDCl3) δ 2.30 (d, 1H, J ) 7.0 Hz), 3.26 (dd, 1H, J
) 5.0, 5.0 Hz), 3.47 (app d, 1H, J ) 7.0 Hz), 4.0-4.03 (m, 1H),
4.07-4.10 (m, 1H), 4.58 (d, 1H, J ) 20 Hz), 4.70 (d, 1H, J )
20 Hz), 5.95 (ddd, 1H, J ) 2.0, 5.0, 10 Hz), 6.1 (ddd, 1H, J )
16.5, 4, 3 Hz), 7.34-7.40 (m, 5H); 13C NMR (125 MHz, CDCl3)
δ 46.4, 57.2, 69.8, 71.5, 126.6, 127.9, 128.5, 133.4, 137.9; MS
(EI) m/e 218 (M)+, 189, 127, 91; HRMS (EI) calcd for
Gen er a l P r oced u r e for th e Syn th esis of 11. Epoxide 5
(152.5 mg, 0.5 mmol) in THF (2 mL) was added over 15 min
to a solution (THF, CH3CN, or THF/H2O, 5 mL) of Pd(PPh3)4
(5-15 mmol %) and nucleophile (0.6 mmol) under an Ar
atmosphere. The reaction was monitored by TLC until
completion. H2O was added to the reaction mixture followed
by extraction with EtOAc (2 × 5 mL). The combined organics
were washed with brine and dried over MgSO4. Concentration
of the organic solution and purification of crude product by
flash chromatography gave the alcohol 11.
C
13H14O3: 218.0942, found 218.0945.
r el-(1R,4S,5S,6R)-5-Br om o-4-[(ter t-bu tyldim eth yl)silyl]-
oxy-7-a za bicyclo[4.1.0]h ep t-2-en e (10a ). To a solution of
azido alcohol 6f (60 mg, 0.172 mmol) in toluene (3.5 mL) was
added PPh3 (56 mg, 0.215 mmol). The reaction mixture was
stirred at rt for 1 h followed by heating at reflux for 3 h. The
reaction mixture was allowed to cool and was concentrated
under reduced pressure. Purification of the resulting oil by
flash chromatography (petroleum ether/EtOAc, 8:1) gave aziri-
dine 10a (30 mg, 57%) as an oily solid: IR (neat) 3312, 3037,
2954, 2929, 2857, 1597, 1466, 1388, 1361, 1254, 1091, 838, 777
r el-(1R,4S,5R,6S)-Dim eth yl 2-[5-br om o-6-(ter t-bu tyld i-
m eth ylsilyl)oxy-4-h ydr oxy-2-cycloh exen ylm alon ate (11a).
Epoxide 5 (152.5 mg, 0.5 mmol) in THF (2 mL) was added over
15 min to a THF solution (5 mL) of Pd(PPh3)4 (5 mol %) and
freshly prepared dimethyl sodiomalonate (NaH, 60% suspen-
sion in oil, 24 mg, 0.6 mmol and dimethyl malonate, 80 mg,
0.6 mmol). The reaction was monitored by TLC until comple-
tion. H2O was added to the reaction mixture followed by
extraction with EtOAc (2 × 5 mL). The combined organics
were washed with brine and dried over MgSO4. Concentration
of the organic solution and purification of crude product by
flash chromatography (hexanes/EtOAc, 3:1) gave the alcohol
11a (201 mg, 92%) as a clear oil: IR (film) 3510, 2954, 2856,
1754, 1737, 1258, 1067, 838 cm-1; 1H NMR (300 MHz, CDCl3)
δ 0.15 (s, 3H), 0.19 (s, 3H), 0.89 (s, 9H), 2.36 (d, 1H, J ) 7.5
Hz), 2.88-2.91 (m, 1H), 3.73 (s, 3H), 3.77 (s, 3H), 3.99 (d, 1H,
J ) 6 Hz), 4.21-4.23 (m, 2H), 4.35-4.39 (m, 1H), 5.73-5.84
(m, 2H); 13C NMR (75 MHz, CDCl3) δ -4.22, -3.60, 18.22,
25.99, 45.15, 52.51, 52.70, 60.40, 67.01, 70.39, 127.85, 128.14,
1
cm-1; H NMR (500 MHz, CDCl3) δ 0.06 (s, 3H), 0.11 (s, 3H),
0.86 (s, 9H), 2.49 (dd, 1H, J ) 4.0, 4.0 Hz), 2.88 (dd, 1H, J )
2.3, 2.3 Hz), 4.39 (ddd, 1H, J ) 2.0, 2.0, 6.0 Hz), 4.45 (m, 1H),
5.79 (dd, 1H, J ) 6.0, 9.9 Hz), 6.39 (dd, 1H, J ) 4.9, 9.9 Hz);
13C NMR (125 MHz, CDCl3) δ -4.8, -4.5, 17.7, 25.6, 29.1, 39.0,
46.9, 68.4, 125.3, 132.1; MS (EI) m/e 304 (M)+, 246 (M - H -
C4H9)+, 224 (M - Br)+, 166, 92, 75; HRMS (EI) calcd for C12H22
-
BrNOSi (M)+ 303.0654, found 303.0661.
r el-(1R,4S,5S,6R)-7-Ben zyl-5-br om o-4(ter t-bu tyldim eth -
ylsilyl)oxy-7-a za bicyclo[4.1.0]h ep t-2-en e (10b). A solution
of CCl4 (213 µL, 2.20 mmol) and PPh3 (230 mg, 262 mmol) in
MeCN (19 mL) was stirred at rt for 1 h. Amino alcohol 6c (91
mg, 0.22 mmol) in MeCN (9 mL) was added via cannula
followed by the addition of Et3N (154 µL, 1.10 mmol). The
solution was stirred at rt for 12 h and then at reflux for 2 h.
Concentration of the solution onto Na2SO4 and purification via
flash chromatography (petroleum ether/EtOAc, 20:1) gave
aziridine 10b (49 mg, 57%) as a clear oil: IR (neat) 3029, 2953,
2928, 2855, 1496, 1466, 1396, 1361, 1253, 1083, 836, 777, 733,
168.28, 168.81. HRMS (EI) calcd for (M - C4H9)+ C13H20
NBrO6Si 379.0213, found 379.0220.
-
Gen er a l P r oced u r e for th e Syn th esis of Ca r bon a tes
12. A solution of 11a -e (1 equiv) and pyridine (6 equiv) in
CH2Cl2 (0.1 M) was cooled to 0 °C and treated dropwise with
methyl chloroformate (5 equiv). The reaction mixture was
stirred at 0 °C for 3 h and then at rt for 3 h. The reaction
mixture was then washed with 1 M HCl, H2O, and brine, and
the organic solution was dried over Na2SO4. Concentration
of the organic solution under reduced pressure and purification
of the resulting oil by flash chromatography (4:1 hexanes:
EtOAc) gave 12a -e in 90-93% yield.
r el-(1R,4S,5R,6S)-Dim eth yl 2-[5-Br om o-6-(ter t-bu tyld i-
m eth ylsilyl)oxy(4-m eth oxycar bon yl)oxy-2-cycloh exen yl]-
m a lon a te (12a ): colorless oil, IR (film) 2930, 2857, 1752, 1441,
1266, 838 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.16 (s, 3H), 0.20
(s, 3H), 0.90 (s, 9H), 2.92-2.96 (m, 1H), 3.73 (s, 3H), 3.77 (s,
3H), 3.80 (s, 3H), 4.02 (d, 1H, J ) 6.9 Hz), 4.19-4.23 (dd, 1H,
J ) 5.4, 7.8 Hz), 4.28-4.32 (dd, 1H, J ) 3.9, 7.5 Hz), 5.37 (m,
1H), 5.75-5.81 (ddd, 1H, J ) 2.4, 3.9, 10.5 Hz), 5.86-5.90 (dd,
1H, J ) 2.4, 10.2 Hz); 13C NMR (75 MHz, CDCl3) δ -4.31,
1
696 cm-1; H NMR (300 MHz, CDCl3) δ 0.10 (s, 3H), 0.14 (s,
3H), 0.91 (s, 9H), 2.09 (dd, 1H, J ) 3.6, 6.0 Hz), 2.48 (dd, 1H,
J ) 1.9, 6.0 Hz), 3.23 (d, 1H, J ) 14 Hz), 3.94 (d, 1H, J ) 13.6
Hz), 4.13 (dd, 1H, J ) 3.0, 5.6 Hz), 4.46 (dd, 1H, J ) 4.9, 4.9
Hz), 5.73 (dd, 1H, J ) 3.6, 9.9 Hz), 6.19 (ddd, 1H, J ) 1.3, 4.0,
9.6 Hz), 7.25-7.39 (m, 5H); 13C NMR (75 MHz, CDCl3) δ -4.6,
-4.4, 18.2, 25.9, 36.7, 47.1, 51.9, 63.3, 70.7, 124.5, 126.8, 127.6,
128.2, 127.9, 131.8, 138.6; MS (EI) m/e 396 (M)+, 338 (M -
C4H9)+, 314 (M - Br)+, 264, 183, 91; HRMS (EI) calcd for
C
15H19BrNOSi 336.0419, found 336.0427.
r el-(1R,4S,5S,6R)-6-Br om o-4-[(ter t-bu tyldim eth yl)silyl]-
oxy-7-(p-tolu en esu lfon yla m in o)-7-a za bicyclo[4.1.0]h ep t-
2-en e (10c). A solution of alcohol 6d (40 mg, 0.84 mmol) and