Cyclization Using Indirect Electrolysis
J . Org. Chem., Vol. 61, No. 2, 1996 683
To a stirred mixture of the above product, 4-fluorophenol
(512 mg, 4.57 mmol), and DMAP (46.6 mg, 0.38 mmol) in dry
ClCH2CH2Cl (10 mL) at 0 °C was slowly added a solution of
DCC (1.03 g, 4.99 mmol) in ClCH2CH2Cl (5 mL), and the
mixture was stirred for 14 h at rt. After dilution with Et2O,
the mixture was filtered through Celite and then evaporated.
Column chromatography of the product on silica gel with
hexane-AcOEt (19:1 v/v) as the eluent provided 42 (572 mg,
as above, 35 (441 mg, 1.07 mmol) was converted into 37 (308
mg, 97%) as a colorless oil: [R]21 +2.4° (c 1.23, CHCl3); IR
D
(neat) 3500, 1740, 1720, 1660 cm-1; 1H NMR (300 MHz) δ 0.99
(t, 3H, J ) 7.5 Hz), 1.52-1.80 (m, 2H), 2.28-2.42 (br s, 1H),
2.57-2.70 (m, 1H), 3.75-3.90 (m, 2H), 4.88 (dd, 2H, J ) 1.8,
4.4 Hz), 6.24 (dt, 1H, J ) 1.8, 15.7 Hz), 7.04-7.06 (m, 4H),
7.15 (dt, 1H, J ) 4.4, 15.7 Hz); MS m/ z 296 (M+); HRMS calcd
for C15H17FO5 (M+) 296.1060, found 296.1056.
44% for two steps) as a colorless oil: IR (neat)1740, 1660 cm-1
;
Using the same method as above, 37 (61 mg, 0.20 mmol)
1H NMR (300 MHz) δ 0.08 (s, 6H), 0.96 (s, 9H), 4.41 (dd, 2H,
J ) 2.5, 3.3 Hz), 6.30 (dt, 1H, J ) 2.5, 15.3 Hz), 7.07-7.08 (m,
4H), 7.25 (dt, 1H, J ) 3.3, 15.3 Hz); MS m/ z 310 (M+); HRMS
calcd for C16H23FO3Si (M+) 310.1401, found 310.1443.
was transformed into 39 (63 mg, 85%) as a colorless oil: [R]21
D
-3.8° (c 0.80, CHCl3); IR (neat) 1750, 1730, 1660 cm-1 1H
;
NMR (300 MHz) δ 0.99 (t, 3H, J ) 7.4 Hz), 1.64-1.88 (m, 2H),
2.79-2.90 (m, 1H), 3.52 (dd, 1H, J ) 5.1, 10.3 Hz), 3.61 (dd,
1H, J ) 8.2, 10.3 Hz), 4.88-4.91 (m, 2H), 6.26 (dt, 1H, J )
1.9, 15.7 Hz), 7.03-7.09 (m, 4H), 7.15 (dt, 1H, J ) 4.4, 15.7
Hz); MS m/ z 358 (M+); HRMS calcd for C15H16BrFO4 (M+)
358.0216, found 358.0200.
Sta n d a r d P r oced u r e for In d ir ect Electr or ed u ction .
The electrolysis was carried out in dry DMF (about 10 mL)
containing a supporting electrolyte (0.1 M Et4NClO4), the
substrate (amount used is shown in each experiment), a proton
source (NH4ClO4 200 mol %), and [Ni(cyclam)](ClO4)2 (10 mol
%), potentionstatically at -1.5 V vs Ag/AgCl using glassy
carbon graphite (0.5 × 0.5 × 0.5 cm3) as the cathode, under
N2 bubbling using an H-type divided cell separated by a
cationic exchange membrane (Nafion 117) at rt. The reaction
was monitored by TLC. After the reaction, the mixture was
diluted with H2O and then thoroughly extracted with Et2O.
The combined extracts were washed with brine, dried (MgSO4),
and evaporated. The product was purified by column chro-
matography on silica gel.
(()-(4R*,5R*)-2-E t h oxy-4-m et h yl-5-p h en yl-3,4,5,6-t et -
r a h yd r o-2H-p yr a n s (44). Using the standard procedure, 12
(144 mg, 0.48 mmol) was converted to 44 (17 mg, 16%) as a
colorless oil: 1H NMR (300 MHz) δ 0.71-0.79 (m, 3H), 1.19-
1.30 (m, 3H), 1.85-1.91 (m, 1H), 2.39-2.49 (m, 1H), 3.44-
3.54 (m, 2H), 3.72-3.85 (m, 2H), 4.90-4.91 (m, 1H), 7.19-
7.34 (m, 5H); HRMS calcd for C14H20O2 (M+) 220.1463, found
220.1474.
(()-(4R*,5R*)-2-Eth oxy-4-eth yl-5-ph en yl-3,4,5,6-tetr ah y-
d r o-2H-p yr a n s (45). The indirect electroreduction of 13 (193
mg, 0.62 mmol) provided 45 (42 mg, 29%) as a colorless oil:
1H NMR (300 MHz) δ 0.74 (t, 3H, J ) 7.4 Hz), 1.20-1.33 (m,
3H), 1.40-1.50 (m, 1H), 1.65-1.75 (m, 1H), 1.91-2.00 (m, 1H),
2.13-2.18 (m, 1H), 2.51-2.70 (m, 1H), 3.45-3.58 (m, 2H),
3.72-3.83 (m, 2H), 4.80-4.95 (m, 1H), 7.19-7.34 (m, 5H);
HRMS calcd for C15H22O2 (M+) 234.1620, found 234.1603.
(()-(4S*,5R*)-2-Eth oxy-4-[(m eth oxyca r bon yl)m eth yl]-
5-p h en yl-3,4,5,6-tetr a h yd r o-2H-p yr a n s (46). Similarly, 14
(123 mg, 0.35 mmol) was transformed into 46 (72 mg, 75%) as
a colorless oil: 1H NMR (300 MHz) δ 1.23-1.29 (m, 3H), 1.90-
2.13 (m, 2H), 2.19-2.29 (m, 1H), 2.34-2.74 (m, 2H), 3.53-
3.55 (m, 3H), 3.71-4.00 (m, 2H), 4.57-4.91 (m, 1H), 7.15-
7.36 (m, 5H); HRMS calcd for C15H19O4 (M+ - Me) 263.1284,
found 263.1292.
A mixture of 42 (570 mg, 1.84 mmol) and AcOH-H2O (3:1
v/v, 16 mL) in THF (4 mL) was stirred for 10 h at rt. After
dilution with AcOEt, the mixture was neutralized with satu-
rated NaHCO3 under cooling with ice. The organic layer was
washed with brine, dried (Na2SO4), and evaporated to give a
residue, which was purified by column chromatography on
silica gel. Elution with hexane-AcOEt (3:1 v/v) afforded 43
(324 mg, 90%) as a colorless oil: IR (neat) 3400, 1740, 1660
cm-1; 1H NMR (300 MHz) δ 2.22-2.38 (br s, 1H), 4.41 (m, 2H),
6.30 (dt, 1H, J ) 2.2, 15.8 Hz), 7.06-7.08 (m, 4H), 7.25 (dt,
1H, J ) 3.6, 15.8 Hz); MS m/ z 196 (M+); HRMS calcd for
C10H9FO3 (M+) 196.0536, found 196.0554.
(-)-p-Flu or oph en yl (2E)-4-[((2′R)-2′-((ter t-Bu tyld im eth -
ylsiloxy)m eth yl)bu ta n oyl)oxy]-2-bu ten oa te (35). To a
stirred solution of the crude acid, which was prepared from
33 (305 mg, 0.78 mmol) as in the previous description, 43 (210
mg, 1.07 mmol), and DMAP (13 mg, 0.11 mmol) in dry ClCH2-
CH2Cl (5 mL) at 0 °C was slowly added a solution of DCC (287
mg, 1.39 mmol) in dry ClCH2CH2Cl (1 mL), and the mixture
was stirred for 12 h at rt. Dilution with Et2O, followed by
filtration through Celite and evaporation of the filtrate, gave
a residue, which was subjected to column chromatography on
silica gel. Elution with hexane-AcOEt (19:1 v/v) yielded 35
(441 mg, 100%) as a colorless oil: [R]21D -0.96° (c 0.94, CHCl3);
1
IR (neat) 1740, 1720, 1660 cm-1; H NMR (300 MHz) δ 0.05
(s, 6H), 0.87 (s, 9H), 0.96 (t, 3H, J ) 7.5 Hz), 1.52-1.72 (m,
2H), 2.55-2.64 (m, 1H), 3.76 (dd, 1H, J ) 5.5, 9.8 Hz), 3.82
(dd, 1H, J ) 8.0, 9.8 Hz), 4.83-4.86 (m, 2H), 6.23 (dt, 1H, J )
1.8, 15.3 Hz), 7.06-7.08 (m, 4H), 7.15 (dt, 1H, J ) 4.4, 15.3
Hz); MS m/ z 353 (M+ - t-Bu); HRMS calcd for C21H31FO5Si
(M+ - t-Bu) 353.1221, found 353.1222.
(-)-Eth yl (2E)-4-[((2′R)-2′-(Hyd r oxym eth yl)bu ta n oyl)-
oxy]-2-bu ten oa te (36). A mixture of 34 (706 mg, 2.05 mmol)
and AcOH-H2O (1:1 v/v, 6 mL) in THF (3 mL) was stirred for
12 h at 40 °C. After neutralization with saturated NaHCO3
under cooling with ice, the mixture was thoroughly extracted
with Et2O. The combined extracts were washed with brine,
dried (Na2SO4), and evaporated. Column chromatography of
the product on silica gel with hexane-AcOEt (3:1 v/v) provided
36 (472 mg 96%) as a colorless oil: [R]21D -1.1° (c 0.93, CHCl3);
1
IR (neat) 3450, 1720, 1655, cm-1; H NMR (300 MHz) δ 0.98
(t, 3H, J ) 7.2 Hz), 1.29 (t, 3H, J ) 7.2 Hz), 1.59-1.81 (m,
2H), 2.09-2.22 (br s, 1H), 2.56-2.66 (m, 1H), 3.72-3.82 (m,
2H), 4.21 (q, 2H, J ) 7.2 Hz), 4.80 (dd, 2H, J ) 2.2, 4.5 Hz),
6.05 (dt, 1H, J ) 2.2, 15.4 Hz), 6.95 (dt, 1H, J ) 4.5, 15.4 Hz).
Anal. Calcd for C11H18O5: C, 57.38; H, 7.88. Found: C, 57.26;
H, 7.84.
(()-2-Eth oxy-4-[(ph en ylth io)m eth yl]-3,4,5,6-tetr ah ydr o-
2H-p yr a n s (47). Similarly, 27 (48 mg, 0.14 mmol) was
converted into 47 (10 mg, 27%) as a colorless oil: IR (CHCl3)
1130 cm-1 1H NMR (300 MHz) δ 1.20 (t, 3H, J ) 7.0 Hz),
;
2.16-2.27 (m, 1H), 2.73-2.90 (m, 2H), 3.39-3.81 (m, 4H), 4.85
(br s, 1H), 7.14-7.40 (m, 5H); HRMS calcd for C14H20O2S (M+)
252.1184, found 252.1177.
(-)-E t h yl (2E)-4-[((2′R)-2′-(Br om om et h yl)b u t a n oyl)-
oxy]-2-bu ten oa te (38). A mixture of 36 (112 mg, 0.49 mmol),
CBr4 (242 mg, 0.73 mmol), and PPh3 (153 mg, 0.58 mmol) in
dry CH2Cl2 (5 mL) was stirred for 3.5 h at rt. Evaporation of
the solvent, followed by column chromatography of the product
on silica gel with hexane-AcOEt (9:1 v/v) as the eluent,
provided 38 (135 mg, 95%) as a pale yellowish oil: [R]21D -4.9°
(c 0.91, CHCl3); IR (neat) 1720, 1655 cm-1; 1H NMR (300 MHz)
δ 0.97 (t, 3H, J ) 7.5 Hz), 1.30 (t, 3H, J ) 7.2 Hz), 1.68-1.84
(m, 2H), 2.76-2.84 (m, 1H), 3.48 (dd, 1H, J ) 5.1, 9.9 Hz),
3.59 (dd, 1H, J ) 8.1, 9.9 Hz), 4.21 (q, 2H, J ) 7.2 Hz), 4.79-
4.84 (m, 2H), 6.05 (dt, 1H, J ) 1.9, 15.7 Hz), 6.95 (dt, 1H, J )
3.8, 15.7 Hz). Anal. Calcd for C11H17BrO4: C, 45.07; H, 5.84.
Found: C, 45.25; H, 5.73.
(4R,5R)-2-Eth oxy-5-eth yl-4-[(m eth oxycar bon yl)m eth yl]-
3,4,5,6-tetr a h yd r o-2H-p yr a n s (49). (A) Using the same
method as above, 489 (29 mg, 0.09 mmol) was transformed into
a 4:1 mixture of 49 (18.0 mg, 83%), the spectral data of which
were consistent with those of the authentic sample.9
(B) Similarly, 509 (32 mg, 0.10 mmol) was converted into
the trans-substituted 49 (21 mg, 88%), all properties of which
were identical with those of authentic sample.9
4-Acetoxy-2-p h en yl-1-bu ten e (54). The electrolysis of 15
(103 mg, 0.38 mmol) gave 54 (42 mg, 58%) as a colorless oil:
IR (neat) 1730, 1635 cm-1; 1H NMR (300 MHz) δ 2.01 (s, 3H),
3.64-3.72 (m, 1H), 4.25-4.38 (m, 2H), 5.09-5.18 (m, 2H),
5.93-6.05 (m, 1H), 7.20-7.38 (m, 5H). Anal. Calcd for
C12H14O2: C, 75.76; H, 7.42. Found: C, 75.71; H, 7.54.
(-)-p-F lu or op h en yl (2E)-4-[((2′R)-2′-(Br om om eth yl)bu -
ta n oyl)oxy]-2-bu ten oa te (39). Using the same procedure