Cleavage of π-Deficient Heterocyclic Sulfones
J . Org. Chem., Vol. 65, No. 13, 2000 4173
Further elution (EtOAc/hexane, 1:1) gave recovered 1b (31 mg,
10%). Evaporation of the reaction mixture and direct column
chromatography also gave 3b with similar yield and purity.
Treatment of 1b (157 mg, 0.5 mmol) by procedure C gave
3b (78 mg, 91%).
Dieth yl Octa n ed ioa te (Dieth yl Su ber a te) (3d ). Treat-
ment of 1d (186 mg, 0.5 mmol) by procedure D gave 3d (101
mg, 88%) with spectra identical to those of an authentic
sample:28 GC/MS purity (>99%); MS m/z 185 (80, M+ - OEt),
143 (100).
3J F-3b ) 37.6 Hz); MS (APCI) m/z 391 (100, MH+). Anal. Calcd
for C16H23FN2O6S (390.44): C, 49.22; H, 5.94; N, 7.18. Found:
C, 48.88; H, 6.30; N, 6.84.
Eth yl 2-Flu or o-2-(pyr im idin -2-ylsu lfon yl)h ept-6-en oate
(5f). Treatment of 1f (596 mg, 2.0 mmol) by procedure E gave
5f (556 mg, 88%) as an oil: 1H NMR δ 1.28 (t, J ) 7.1 Hz,
3H), 1.35-1.68 (m, 2H), 2.08-2.18 (m, 2H), 2.45-2.68 (m, 2H),
4.32 (q, J ) 7.1 Hz, 2H), 4.95 (dm, J ) 9.9 Hz, 1H), 5.01 (dm,
J ) 16.6 Hz, 1H), 5.65-5.75 (m, 1H), 7.65 (t, J ) 4.8 Hz, 1H),
8.98 (d, J ) 4.9 Hz, 2H); 13C NMR δ 14.4, 22.3 (3J ) 2.0 Hz),
30.5 (d, 2J ) 19.8 Hz), 33.4, 63.9, 107.4 (d, 1J ) 234.2 Hz),
Eth yl Hep t-6-en oa te (3f). Treatment of 1f (170 mg, 0.57
mmol) with Bu3SnH (1.14 mmol) by procedure C (chromatog-
raphy: pentane f 10% EtOAc/pentane) gave 3f 30 (75 mg, 84%)
contaminated (∼5-10%, 1H NMR) by tin compound(s). Hy-
drolysis (NaOH/H2O/MeOH) of this material gave 6-heptenoic
acid with spectra identical to those of authentic sample.28
Analogous treatment of 1f by procedure C in C6D6 and direct
2
116.4, 124.9, 137.3, 159.2, 163.5, 163.8 (d, J ) 25.3 Hz); 19F
3
3
NMR δ -158.6 (dd, J F-3a ) 11.9 Hz, J F-3b ) 36.9 Hz); MS
(APCI) m/z 317 (100, MH+). Anal. Calcd for C13H17FN2O4S
(316.36): C, 49.36; H, 5.42; N, 8.86. Found: C, 49.39; H, 5.51;
N, 8.80.
Eth yl 2-F lu or o-2-(p yr id in -2-ylsu lfon yl)h exa n oa te (6a ).
Treatment of 2a (428 mg, 1.5 mmol) with KH (2.0 mmol) and
Selectfluor (2.5 mmol) (2 h) by procedure E gave 6a (414 mg,
91%; viscous oil): 1H NMR δ 0.90 (t, J ) 6.8 Hz, 3H), 1.16-
1.52 (m, 7H), 2.30-2.73 (m, 2H), 4.31 (q, J ) 7.2 Hz, 2H), 7.60
(ddd, J ) 1.4, 4.7, 7.6 Hz, 1H), 7.98 (dt, J ) 1.7, 7.6 Hz, 1),
8.09 (dt, J ) 1.1 Hz, 7.8 Hz, 1), 8.73 (ddd, J ) 1.0, 1.7, 4.8 Hz,
1
analysis of the aliqouts (0.25 h, 0.5 h, 1 h) by H NMR (C6D6)
showed that integration of the characteristic signals for the
vinylic protons at δ 5.54-5.75 (m, 1, H6) and 4.90-5.02 (m,
3, H2,7,7′) remained constant ((5%) compared with the signals
for the methylene protons at δ 3.88 (1f) and 4.01 (3f) from the
ester groups. Washing of the C6D6 solution with D2O/NaHCO3
and 1H NMR of D2O layer showed only signals for 13.
Treatment of 1f (149 mg, 0.5 mmol) by procedure D also
gave 3f (69 mg, 89%): GC/MS purity (99%); MS m/z 156 (5),
88 (100).
Eth yl 2-Deu ter ioh exa n oa te (4a ). Treatment of 1a (143
mg, 0.5 mmol) with Bu3SnD (0.268 mL, 291 mg, 1 mmol) by
procedure C (2 h) gave 4a (65 mg, 90%): 1H NMR spectra
corresponded with those of 3a with 50% reduction in the
intensity of signals28 at δ 2.26 (t, J ) 7.7 Hz, 1H, 2-CHD); MS
(CI) m/z 146 (100, MH+ [C8H16DO2]).
3
1); 13C NMR δ 14.2, 14.4, 22.8, 25.1 (d, J ) 2.0 Hz), 30.7 (d,
2J ) 19.7 Hz), 63.9, 107.5 (d, 1J ) 231.4 Hz), 126.32, 128.8,
138.68, 150.78, 154.2, 164.0 (d, 2J ) 24.1 Hz); 19F NMR δ
-159.3 (dd, 3J F-3a ) 10.0 Hz, 3J F-3b ) 38.7 Hz); IR (neat) 2964,
1758, 1353, 1266, 1174, 734 cm-1; MS (CI) m/z 304 (100, MH+).
Anal. Calcd for C13H18FNO4S (303.3): C, 51.47; H 5.98; N, 4.62.
Found: C, 51.39; H, 6.12; N, 4.51.
Eth yl 2-F lu or oh exa n oa te (7a ). Treatment of 5a (304 mg,
1 mmol) with Bu3SnH (1.75 mmol) by procedure C gave 7a
(154 mg, 95%; oil) with data as reported.31a
Analogous treatment of 6a (303 mg, 1 mmol) with Bu3SnH
(2.0 mmol) and AIBN (0.2 mmol) (28 h) [additional Bu3SnH
(1.0 mmol) and AIBN (0.2 mmol) were added after 14 h] gave
7a (97 mg, 60%). Further elution (EtOAc/pentane, 1:1) gave
recovered 5b (61 mg, 20%).
E t h yl 2-F lu or o-2-(p yr im id in -2-ylsu lfon yl)h exa n oa t e
(5a ). P r oced u r e E. KH [(571 mg, 35%/mineral oil, 5 mmol)
or (220 mg, 5.5 mmol, dried/pressed between filter paper)] in
a flame-dried flask under Ar was washed (dried hexane, dried
Et2O), and dried THF (25 mL) was added. The suspension was
cooled (∼0 °C, ice bath), and compound 1a (1.14 g, 4 mmol) in
dried THF (15 mL) was added (syringe). The solution was
stirred (0 °C for 15 min, ambient temperature for 60 min,
cooled to 0 °C), and Selectfluor (2.13 g, 6 mmol) was added in
one portion. After 15 min, dried DMF (15 mL) was added
(syringe), the ice bath was removed after 5 min, and stirring
was continued at ambient temperature for 2 h. The reaction
mixture was cooled to ∼0 °C (ice bath), and CHCl3 (30 mL)
and saturated NH4Cl/H2O (15 mL) were slowly added. The
organic layer was separated after 5 min, and the aqueous layer
was extracted (CHCl3, 2 × 25 mL). The combined organic
phase was washed (saturated NaHCO3/H2O, brine), dried
(MgSO4), evaporated, and chromatographed (50 f 90% EtOAc/
hexanes)] to give 5a (1.12 g, 92%) as a slightly yellow solidified
oil: 1H NMR δ 0.91 (t, J ) 6.6 Hz, 3H), 1.30 (t, J ) 7.1 Hz,
3H), 1.25-1.60 (m, 4H), 2.43-2.72 (m, 2H), 4.35 (q, J ) 7.1
Treatment of 5a (1 mmol) with Bu3SnH (1.3 mmol) gave 7a
(85%) [TLC: 5a (∼5-10%)].
Eth yl 2-F lu or oocta n oa te (7b). Treatment of 5b (664 mg,
2 mmol) with Bu3SnH (3.5 mmol) by procedure C (chromatog-
raphy: hexane f 10% EtOAc/hexane) gave 7b (334 mg, 88%;
oil) with data as reported:13 GC/MS purity (99%); MS m/z 190
(5, M+), 106 (100).
Treatment of 5b (332 mg, 1 mmol) by procedure D gave 7b
[163 mg, 86%; GC (>99%)].
Dieth yl 2-F lu or oocta n ed ioa te (7d ). Treatment of 5d (195
mg, 0.5 mmol) by procedure C [chromatography (hexane f
10% EtOAc/hexane)] gave 7d (109 mg, 88%): 1H NMR δ 1.25
(t, J ) 7.1 Hz, 3H), 1.31 (t, J ) 7.2 Hz, 3H), 1.35-1.53 (m,
4H), 1.65 (quint, J ) 7.5 Hz, 2H), 1.82-1.95 (m, 2H), 2.25 (t,
J ) 7.4 Hz, 2H), 4.12 (q, J ) 7.2 Hz, 2H), 4.26 (q, J ) 7.1 Hz,
2H), 4.89 (dt, J ) 49.4, 5.9 Hz, 1H); 13C NMR δ 14.5, 14.6,
3
2
24.4 (d, J ) 2.9 Hz), 25.0, 28.9, 32.6 (d, J ) 21.1 Hz), 34.5,
60.7, 61.8, 89.3 (d, 1J ) 183.9 Hz), 170.4 (d, 2J ) 23.6 Hz),
Hz, 2H), 7.62 (t, J ) 4.9 Hz, 1H), 8.98 (d, J ) 4.9 Hz, 2H); 13
C
NMR δ 14.1, 14.4, 22.8, 25.1, 30.9 (d, 2J ) 19.7 Hz), 63.9, 107.6
(d, 1J ) 232.8 Hz), 125.0, 159.3, 163.7, 163.9 (d, 2J ) 25.2 Hz);
19F NMR δ -158.8 (dd, 3J F-3a ) 10.9 Hz, 3J F-3b ) 37.8 Hz); IR
(neat) 2963, 1751, 1567, 1347 cm-1; MS (EI) m/z 304 (42, M+),
197 (50), 79 (100). Anal. Calcd for C12H17FN2O4S (304.3): C,
47.36; H, 5.63; N, 9.20. Found: C, 47.57; H, 5.72; N, 9.19.
Dieth yl 2-F lu or o-2-(p yr im id in -2-ylsu lfon yl)octa n ed io-
a te (5d ). Treatment of 1d (186 mg, 0.5 mmol) by procedure E
gave 5d (166 mg, 85%): 1H NMR δ 1.22 (t, J ) 7.1 Hz, 3H),
1.30 (t, J ) 7.2 Hz, 3H), 1.40 (quint, J ) 7.3 Hz, 2H), 1.52-
1.66 (m, 4H), 2.26 (t, J ) 7.4 Hz, 2H), 2.48-2.66 (m, 2H), 4.08
(q, J ) 7.1 Hz, 2H), 4.34 (q, J ) 7.1 Hz, 2H), 7.65 (t, J ) 4.8
Hz, 1H), 8.95 (d, J ) 4.9 Hz, 2H); 13C NMR δ 14.3, 14.6, 22.6
174.0; 19F NMR δ -192.6 (dt, J F-2 ) 49.0 Hz, J F-3a,b ) 25.0
Hz); GC/MS purity (>99%); MS m/z 203 (45, M+ - OEt), 88
(100). Anal. Calcd for C12H21FO4 (248.30): C, 58.05; H, 8.53.
Found: C, 58.25; H, 8.75.
2
3
Eth yl 2-F lu or oh ep t-6-en oa te (7f). Treatment of 5f (158
mg, 0.5 mmol) with Bu3SnH (1 mmol) by procedure C [chro-
matography (hexane f 10% EtOAc/hexane)] gave 7f (79 mg,
91%): 1H NMR δ 1.32 (t, J ) 7.1 Hz, 3H), 1.58 (“quint” J )
8.2 Hz, 2H), 1.85-1.96 (m, 2H), 2.11 (“q”, J ) 6.7 Hz, 2H),
4.29 (q, J ) 7.1 Hz, 2H), 4.90 (dt, J ) 49.5, 5.9 Hz, 1H), 4.98
(dm, J ) 9.9 Hz, 1H), 5.03 (dm, J ) 16.7 Hz, 1H), 5.79 (ddt, J
) 16.9, 10.1, 6.6 Hz, 1H); 13C NMR δ 14.6, 23.9 (d, 3J ) 2.8
Hz), 32.1 (d, 2J ) 21.1 Hz), 33.5, 61.9, 89.3 (d, 1J ) 183.9 Hz),
3
2
(d, J ) 2.0 Hz), 24.8, 28.9, 30.9 (d, J ) 19.8 Hz), 34.3, 60.7,
63.9, 107.3 (d, 1J ) 234.4 Hz), 125.1, 159.3, 163.4, 163.7 (d, 2J
2
115.7, 138.2, 170.4 (d, J ) 23.7 Hz); 19F NMR δ -192.6 (dt,
2J F-2 ) 49.5 Hz, 3J F-3a,b ) 25.4 Hz); IR (neat) 2931, 1758, 1738,
) 25.1 Hz), 173.8; 19F NMR δ -158.9 (dd, J F-3a ) 11.3 Hz,
3
(31) (a) Thenappan, A.; Burton, D. J . J . Org. Chem. 1990, 55, 2311-
2317. (b) Brown, D. J .; Hoskin, J . A. J . Chem. Soc. (B) 1971, 2214-
2217.
(30) Vettel, S.; Vaupel, A.; Knochel, P. J . Org. Chem. 1996, 61,
7473-7481.