Pt- and Acid-Catalyzed Enyne Metathesis Reactions
J. Am. Chem. Soc., Vol. 120, No. 33, 1998 8313
1-[12-(Toluene-4-sulfonyl)-12-azabicyclo[9.2.1]tetradeca-1(14),2-
dien-2-yl]ethanone (31). Method A. A suspension of substrate 30
(300 mg, 0.774 mmol) and PtCl2 (21 mg, 0.077 mmol, 10 mol %) in
toluene (80 mL) was stirred for 21 h at 100 °C. Removal of the solvent
in vacuo and flash chromatography (hexanes/ethyl acetate, 6:1 f 4:1)
provided compound 31 as a bright-yellow oil (126 mg, 42%).
Method B. A solution of substrate 30 (1.020 g, 2.632 mmol) and
BF3‚Et2O (20 µL, 0.157 mmol, 6 mol %) in toluene (150 mL) was
stirred for 22 h at ambient temperature. After this period, more BF3‚
Et2O (80 µL, 0.632 mmol, 24 mol %) was added and stirring continued
for 17 h. The orange solution was then concentrated in vacuo. Flash
chromatography (hexanes/ethyl acetate, 7:1 f 4:1) afforded product
31 as a bright-yellow oil (551 mg, 54%): Rf 0.19 (hexanes/ethyl acetate,
4:1); 1H NMR (200 MHz, CDCl3) δ 7.70 (AA′XX′, 2H), 7.26 (AA′XX′,
2H), 6.88 (dd, 1H, J ) 9.6, 7.3 Hz), 5.36 (dt, 1H, J ) 2.1, 2.0 Hz),
4.53 (m, 1H), 4.40 (dt, 1H, J ) 14.6, 2.2 Hz), 3.98 (ddd, 1H, J )
14.6, 2.1 Hz), 2.34 (s, 3H), 2.08 (s, 3H), 2.24-1.17 (m, 14H); 13C
NMR (50 MHz, CDCl3) δ 197.6, 147.5, 143.4, 137.4, 134.6, 132.7,
129.8, 129.7, 127.4, 67.5, 58.5, 32.0, 26.9, 25.9, 25.9, 25.5, 24.9, 24.4,
23.9, 21.5. Anal. Calcd for C22H29NSO3 (387.54): C, 68.18; H, 7.54;
N, 3.61. Found: C, 68.30; H, 7.58; N, 3.65.
1-[12-(Toluene-4-sulfonyl)-12-azabicyclo[9.2.1]tetradec-1(14)-en-
2-yl]ethanone (32). To a solution of dienone 31 (662 mg, 1.708 mmol),
glacial HOAc (108 µL, 1.879 mmol), and Pd(PPh3)4 (40 mg, 0.034
mmol, 2 mol %) in benzene was added n-Bu3SnH (1.15 mL, 4.27 mmol)
dropwise via cannula over 5 min. After the mixture was stirred for 3
h at ambient temperature, the solvent was removed in vacuo and the
residue was purified by flash chromatography (hexanes 300 mL, then
hexanes/ethyl acetate, 10:1 f 6:1) to give product 32 (465 mg, 70%)
as a colorless solid: mp 124-125 °C; Rf 0.46 and 0.42 for both
diastereomers (hexanes/ethyl acetate, 4:1). Major isomer: 1H NMR
(300 MHz, CDCl3) δ 7.63 (AA′XX′, 2H), 7.22 (AA′XX′, 2H), 5.40
(dt, 1H, J ) 1.9, 2.0 Hz), 4.55 (m, 1H), 4.07 (ddd, 1H, J ) 14.9, 5.4,
1.9 Hz), 3.92 (dt, 1H, J ) 14.9, 2.1 Hz); 3.33 (dd, 1 H, J ) 10.3, 3.5
Hz), 2.33 (s, 3H), 2.17 (m, 1H), 1.76 (s, 3H), 1.72-1.48 (m, 2H), 1.42-
1.03 (m, 13H); 13C NMR (75 MHz, CDCl3) δ 207.2, 143.4, 135.4,
134.6, 129.6, 129.1, 127.4, 67.3, 54.9, 53.4, 33.5, 28.0, 26.1, 26.0, 25.5,
24.4, 23.9, 23.2, 22.3, 21.4. Anal. Calcd for C22H31NSO3 (389.56):
C, 67.83; H, 8.02; N, 3.60. Found: C, 67.86; H, 7.94; N, 3.52.
Thiocarbonic Acid O-Phenyl Ester O-{1-[12-(Toluene-4-sulfonyl)-
12-azabicyclo[9.2.1]tetradec-1(14)-en-2-yl]ethyl} Ester (33). A solu-
tion of enone 32 (465 mg, 1.194 mmol) in Et2O (15 mL) was reacted
with LiAlH4 (32 mg, 0.836 mmol) dissolved in Et2O (5 mL). Standard
workup followed by flash chromatography (hexanes/ethyl acetate, 6:1
f 4:1) provided two diastereomeric alcohols (420 mg, 90%) which
exhibit the following physical data: mp 164-165 °C; Rf 0.36 and 0.29
(hexanes/ethyl acetate, 2:1); 1H NMR (300 MHz, CDCl3) δ 7.72
(AA′XX′, 2H), 7.29 (AA′XX′, 2H), 5.34 (dt, 1H, J ) 1.9, 1.8 Hz),
4.59 (m, 1H), 4.19 (m, 2H), 3.53 (v.quint, 1H), 2.40 (s, 3H), 2.22 (m,
2H), 1.53-1.14 (m, 16H), 0.96 (t, 3H, J ) 6.1 Hz); 13C NMR (75
MHz, CDCl3) δ 143.3, 138.1, 134.7, 129.6, 128.4, 127.3, 69.5, 66.9,
55.2, 47.6, 33.4, 26.8, 26.0, 25.9, 25.6, 24.1, 23.3, 22.5, 21.4, 21.1; IR
(KAP) 3531, 3083, 2942, 2864, 2851, 1710, 1596, 1492, 1476, 1453,
1334, 1157, 1092, 1050, 813, 668, 584 cm-1; MS (EI) m/z (relative
intensity) 391 ([M+] 9), 346 (100), 274 (7), 248 (10), 236 (21), 234
(32), 218 (12), 192 (27), 155 (26), 91 (52), 80 (21), 55 (9), 41 (10).
To a solution of this alcohol (diastereomeric mixture, 140 mg, 0.358
mmol) in CH2Cl2 (10 mL) were added PhOC(S)Cl (99 µL, 124 mg,
0.716 mmol) and pyridine (87 µL, 57 mg, 1.074 mmol) via cannula at
0 °C. After the mixture was stirred for 20 h at ambient temperature,
the solvent was removed in vacuo. Flash chromatography (hexanes/
ethyl acetate, 10:1 f 7:1) afforded the title compound 33 as a colorless
solid (119 mg, 63%): mp 61-62 °C; Rf 0.49 (hexanes/ethyl acetate,
4:1). Major isomer: 1H NMR (300 MHz, CDCl3) δ 7.72 (AA′XX′,
2H), 7.41 (m, 2H), 7.29 (m, 3H), 6.95 (AA′XX′, 2H), 5.31 (dt, 1H, J
) 1.8, 1.9 Hz), 5.25 (dd, 1H, J ) 6.2, 5.5 Hz), 4.60 (m, 1H), 4.13 (dd,
2H, J ) 1.9 Hz), 2.56 (m, 1H), 2.36 (s, 3H), 2.26 (m, 1H), 1.59-1.13
(m, 15H), 0.99 (d, 3H, J ) 6.3 Hz); 13C NMR (75 MHz, CDCl3) δ
193.8, 153.0, 143.3, 136.3, 134.5, 129.7, 129.5, 129.2, 127.5, 126.5,
121.7, 83.7, 66.9, 55.4, 44.8, 33.5, 26.7, 26.0, 25.8, 25.2, 24.2, 23.1,
22.6, 21.4, 17.2.
2-Ethyl-12-(toluene-4-sulfonyl)-12-azabicyclo[9.2.1]tetradec-1(14)-
ene (34). To a solution of substrate 33 (115 mg, 0.218 mmol) in toluene
(5 mL) were added AIBN (7 mg, 0.044 mmol, 20 mol %) and n-Bu3SnH
(117 µL, 127 mg, 0.436 mmol). The solution was stirred for 4 h at 75
°C. Removal of the solvent in vacuo and flash chromatography of the
residue (hexanes (300 mL), then hexanes/ethyl acetate, 20:1 f 16:1)
afforded dihydropyrrole 34 as a colorless oil (76 mg, 93%): Rf 0.57
(hexanes/ethyl acetate, 4:1); 1H NMR (300 MHz, CDCl3) δ 7.70
(AA′XX′, 2H), 7.29 (AA′XX′, 2H), 5.22 (dt, 1H, J ) 1.9, 1.8 Hz),
4.60 (m, 1H), 4.09 (ddd, 1H, J ) 14.4, 5.2, 1.9 Hz), 3.92 (dt, 1H, J )
14.3, 1.9 Hz), 2.40 (s, 3H), 2.18 (m, 2H), 1.52-0.86 (m, 17H), 0.44
(t, 3H, J ) 7.3 Hz); 13C NMR (75 MHz, CDCl3) δ 143.2, 140.4, 134.7,
129.5, 127.3, 125.6, 67.2, 53.9, 41.6, 33.4, 30.6, 27.6, 27.2, 26.1, 26.0,
25.9, 24.2, 23.6, 22.4, 21.4, 11.7. Anal. Calcd for C22H33NSO2
(375.58): C, 70.36; H, 8.86; N, 3.73. Found: C, 70.29; H, 8.86; N,
3.68.
2-Ethyl-12-azabicyclo[9.2.1]tetradeca-1(13),11(14)-diene (5). Ac-
cording to the procedure described for the preparation of pyrrole 7, a
solution of dihydropyrrole 34 (76 mg, 0.202 mmol) in 1,3-diamino-
propane (2 mL) was treated with the KAPA reagent (7 mL). Compound
5 was thus obtained as a colorless solid (33 mg, 75%): Rf 0.69 (hexanes/
ethyl acetate, 4:1); 1H NMR (600 MHz, CD2Cl2) δ 7.65 (bs, 1H), 6.40
(t, 1H, J ) 2.0 Hz), 5.87 (t, 1H, J ) 2.0 Hz), 2.53 (m, 2H), 2.21 (m,
1H), 1.61 (m, 1H), 1.57 (m, 1H), 1.52 (m, 1H), 1.30 (m, 1H), 1.36 (m,
2H), 1.2 (m, 2H), 1.15 (m, 1H), 1.08-1.04 (m, 5H), 0.89 (t, 3H, J )
7.4 Hz), 0.49 (bs, 1H), 0.02 (bs, 1H); 13C NMR (150 MHz, CD2Cl2) δ
133.0, 128.9, 115.0, 106.3, 41.1, 33.5, 29.3, 29.1, 28.6, 28.0, 27.4, 26.0,
25.7, 21.9, 12.9.
N-Cyclooct-2-enyl-N-hept-2-ynyl-4-methylbenzenesulfonamide (27).
A solution of enyne 10 (718 mg, 2.262 mmol) in THF (30 mL) was
cooled to -78 °C, and n-BuLi (1.6 M in hexane; 1.36 mL, 2.175 mmol)
was added dropwise at that temperature. After 20 min 1-butyliodide
(0.78 mL, 1.249 g, 6.786 mmol) was added dropwise via cannula and
stirring was continued for 0.5 h. The reaction mixture was then kept
for 5 h at -30 °C prior to slowly warming to ambient temperature.
After 30 h, the mixture was quenched with saturated aqueous NH4Cl
(50 mL) and diluted with ethyl acetate (50 mL). The aqueous phase
was extracted with ethyl acetate (3 × 50 mL), and the combined organic
layers were dried over Na2SO4, filtered, and concentrated. Flash
chromatography of the residue (hexanes/ethyl acetate, 15:1) provided
enyne 27 (718 mg, 85%) as a colorless oil: Rf 0.68 (hexanes/ethyl
acetate, 4:1); 1H NMR (300 MHz, CDCl3) δ 7.75 (AA′XX′, 2H), 7.23
(AA′XX′, 2H), 5.61 (m, 2H), 4.84 (ddd, 1H, J ) 16.6, 7.2, 5.0 Hz),
4.14 (dt, 1H, J ) 18.3, 2.2 Hz), 4.08 (dt, 1H, J ) 18.3, 2.2 Hz), 2.40
(s, 3H), 2.23-2.00 (m, 4H), 1.80-1.20 (m, 12H), 0.86 (t, 3H, J ) 7.1
Hz); 13C NMR (75 MHz, CDCl3) δ 142.8, 138.2, 130.0, 129.1, 128.6,
127.7, 84.9, 75.9, 55.7, 34.5, 33.7, 30.4, 29.0, 26.3, 24.6, 21.9, 21.5,
18.3, 13.6. Anal. Calcd for C22H31NSO2 (373.56): C, 70.74; H, 8.36;
N, 3.75. Found: C, 70.63; H, 8.42; N, 3.79.
4-[Cyclooct-2-enyl(toluene-4-sulfonyl)amino]but-2-ynoic Acid
Methyl Ester (11). To a solution of compound 10 (200 mg, 0.63
mmol) in THF (5 mL) was slowly added n-BuLi (1.6 M in hexane;
0.37 mL, 0.60 mmol) at -78 °C. After 15 min, the suspension was
transferred over a period of 20 min via siphon to a solution of
chloroformic acid methyl ester (119 mg, 1.26 mmol) in THF (2 mL)
at -35 °C. The solution was kept at that temperature for 0.5 h and
then at +10 °C for 15 min. The mixture was quenched with saturated
aqueous NH4Cl (25 mL) and diluted with ethyl acetate (20 mL), the
aqueous phase was extracted with Et2O (3 × 20 mL), and the combined
organic layers were dried over Na2SO4, filtered, and concentrated in
vacuo. Flash chromatography of the residue (hexanes/ethyl acetate,
8:1) gave enyne 11 (161 mg, 68%) as a colorless oil: Rf 0.48 (hexanes/
ethyl acetate, 4:1); 1H NMR (200 MHz, CDCl3) δ 7.76 (AA′XX′, 2H),
7.26 (AA′XX′, 2H), 5.64 (dtd, 1H, J ) 10.7, 9.0, 1.2 Hz), 5.45 (dd,
1H, J ) 10.8, 8.1 Hz), 4.82 (dt, 1H, J ) 7.9, 7.8 Hz), 4.29 (d, 1H, J
) 19.1 Hz), 4.20 (d, 1H, J ) 19.1 Hz), 3.75 (s, 3H), 2.41 (s, 3H),
2.28-2.04 (m, 2H), 1.70-1.22 (m, 8H); 13C NMR (50 MHz, CDCl3)
δ 153.3, 143.4, 137.1, 131.0, 129.4, 127.5, 127.4, 83.7, 75.7, 55.6, 52.6,
34.2, 32.9, 28.7, 26.2, 25.8, 24.4, 21.5.
10-(Toluene-4-sulfonyl)-10-azabicyclo[7.2.1]dodeca-1(12),2-diene-
2-carboxylic Acid Methyl Ester (13). To a solution of enyne 11 (280