B.H. Lipshutz, S. Ghorai / Tetrahedron 66 (2010) 1057–1063
1061
d
16.53 (s, 1H), 7.42–7.39 (m, 1H), 7.06 (s, 4H), 6.81 (d, J¼1.6 Hz,
a white solid (24 mg, 95%). The 1H NMR spectral data obtained was in
accord with data previously reported for this compound.16
1H), 6.73 (d, J¼8.0 Hz, 1H), 4.87 (sep, J¼6.4 Hz, 1H), 4.22 (t,
J¼4.8 Hz, 2H), 4.17 (s, 4H), 3.79 (s, 3H), 3.71 (s, 3H), 3.70–3.45 (m,
PEG), 3.38 (s, 3H), 3.09–3.05 (m, 2H), 2.87–2.80 (m, 2H), 2.62–
2.56 (m, 2H), 2.47 (br s, 12H), 2.40 (s, 6H), 2.33 (t, J¼7.2 Hz, 2H),
2.06 (s, 2.05H), 1.98 (s, 1.05H), 1.80–1.76 (m, 2H), 1.64–1.60 (m,
2H), 1.55–1.46 (m, 2H), 1.35–1.06 (m, 80H), 0.93–0.83 (m, 33H);
4.5.5. (3-Methylcyclopent-3-enyl)(phenyl)methanone (Table 1, Entry
5). The representative procedure was followed using N-allyl-N-(2-
methylallyl)benzamide13 (21.5 mg, 0.10 mmol) and catalyst
2
(8.0 mg, 0.002 mmol). Column chromatography on silica gel (elut-
ing with 20% EtOAc/hexanes) afforded the product as a colorless oil
(18.5 mg, 99%). The 1H NMR spectral data obtained was in accord
with data previously reported for this compound.13
13C NMR (100 MHz, CDCl3):
d 210.5, 172.72, 172.68, 170.9, 170.6,
170.0, 169.8, 150.2, 144.5, 142.54, 142.51, 140.1, 139.9, 139.6, 139.4,
137.9, 133.2, 128.9, 128.6, 128.5, 123.6, 123.4, 121.7, 112.2, 74.2,
71.2, 69.8–69.4 (m, PEG), 68.4, 62.6, 59.8, 59.7, 58.3, 38.7, 36.8,
36.7, 36.6, 36.4, 35.8, 35.0, 33.4, 33.2, 32.6, 32.5, 32.1, 32.04, 32.0,
28.8, 28.4, 28.3, 27.3, 26.3, 25.7, 25.5, 24.4, 24.2, 24.1, 23.7, 22.2,
22.0, 20.42, 20.36, 19.2, 19.16, 19.1, 19.0, 18.9, 11.3; MS (ESI): m/3z
4.5.6. 4-Methyl-2-phenethyl-2,5-dihydrofuran (Table 1, Entry
6). The representative procedure was followed using (3-(2-methyl-
allyloxy)pent-4-enyl)benzene (22 mg, 0.10 mmol) and catalyst 2
(8.0 mg, 0.002 mmol). Column chromatography on silica gel (eluting
with2%EtOAc/hexanes)affordedtheproductasa colorlessoil(19 mg,
98%). IR (neat): 3062, 3027, 2918, 2858, 1668, 1604, 1496, 1454, 1366,
w1271 (Mþ3Na)þ3
.
4.5. General procedure for ring-closing metathesis
1268, 1194, 1061, 1031, 992, 972, 936 cmꢂ1
CDCl3):
7.29 (t, J¼7.2 Hz, 2H), 7.22–7.17 (m, 3H), 5.40 (br s,1H), 4.85
(brs,1H), 4.58–4.47 (m, 2H), 2.78–2.63 (m, 2H),1.89–1.80 (m, 2H),1.76
(s, 3H); 13C NMR (100 MHz, CDCl3):
142.5, 136.5, 128.6, 128.4, 125.8,
;
1H NMR (400 MHz,
Diene (0.10 mmol) and catalyst 2 (7.5 mg, 0.002 mmol) were
both added into a Teflon-coated-stir-bar-containing Biotage 2–5 mL
microwave reactor vial at room temperature, and sealed with
a septum. H2O (1.0 mL; all RCM reaction were conducted at 0.1 M
unless stated otherwise) was added, via syringe, and the resulting
solution was allowed to stir at room temperature for 3 h. The ho-
mogeneous reaction mixture was then diluted with EtOAc (2 mL),
filtered through a bed of silica gel layered over Celite, and the bed
further washed (2ꢃ4 mL) with EtOAc to collect all of the cyclized
material. The volatiles were removed in vacuo to afford the crude
product, which was subsequently purified by flash chromatography
using silica gel (solvent noted) to afford the title compounds.
d
d
123.6, 86.2, 77.9, 38.2, 31.7, 12.5; MS (EI) m/z (%): 188 (8), 110 (7), 91
(24), 83 (100); HRMS (EI) calcd for C13H16O [M]þ¼188.1201, found
188.1209.
4.5.7. 5-Methyl-2-phenyl-3,6-dihydro-2H-pyran (Table 1, Entry
7). The representative procedure was followed using (1-(2-methyl-
allyloxy)but-3-enyl)benzene (20 mg, 0.10 mmol) and catalyst 2
(8.0 mg, 0.002 mmol). Column chromatography on silica gel (eluting
with 2% EtOAc/hexanes) afforded the product as a colorless oil
(17 mg, 99%). The 1H NMR spectral data obtained was in accord with
data previously reported for this compound.17
4.5.1. Diethyl 3-methylcyclopent-3-ene-1,1-dicarboxylate (Table 1,
Entry 1). The representative procedure was followed using diethyl
2-allyl-2-(2-methylallyl)malonate13 (25.5 mg, 0.10 mmol) and cat-
alyst 2 (8.0 mg, 0.002 mmol). Column chromatography on silica gel
(eluting with 16% EtOAc/hexanes) afforded the product as a color-
less oil (21 mg, 93%). The 1H NMR spectral data obtained was in
accord with data previously reported for this compound.14
4.5.8. 3,4-Dimethyl-N-tosyl-2,5-dihydro-1H-pyrrole (Table 1, Entry
8). The representative procedure was followed using 4-methyl-
N,N0-bis(2-methylallyl)benzenesulfonamide (21 mg, 0.075 mmol)
and catalyst 2 (15 mg, 0.0038 mmol). Resulting solution was
allowed to stir at 60 ꢀC for 24 h. Column chromatography on silica
gel (eluting with 5% EtOAc/hexanes) afforded the product as a white
solid (13 mg, 70%). The 1H NMR spectral data obtained was in ac-
cord with data previously reported for this compound.18
4.5.2. Diethyl 3-methylcyclohex-3-ene-1,1-dicarboxylate (Table 1,
Entry 2). The representative procedure was followed using diethyl
2-(but-3-enyl)-2-(2-methylallyl)malonate (27 mg, 0.10 mmol) and
catalyst 2 (8.0 mg, 0.002 mmol). Column chromatography on silica
gel (eluting with 2% EtOAc/hexanes) afforded the product as a col-
orless oil (20.5 mg, 85%). IR (neat): 2979, 2936, 2851, 1735, 1445,
1388, 1366, 1339, 1314, 1286, 1252, 1176, 1079, 1046, 1022, 968,
4.6. Diethyl 2-(but-3-enyl)-2-(2-methylallyl)malonate
To a solution of sodium ethoxide (0.11 g, 1.62 mmol) in EtOH
(5 mL) was added diethyl 2-(2-methylallyl)malonate19 (0.30 g,
1.40 mmol). After 15 min, 4-bromo-1-butene (0.21 mL, 2.10 mmol)
was added and stirred at 22 ꢀC for 24 h. Then the reaction mixture
was quenched with water and extracted with Et2O. The combined
organic layer was washed with water, dried, and concentrated in
vacuo gave yellow liquid, which was subsequently purified by flash
chromatography using silica gel (5% EtOAc/hexanes) to afford the
title compound (0.19 g, 50%) as a colorless liquid. IR (neat): 3078,
2980, 2938, 2873, 1733, 1643, 1448, 1367, 1298, 1264, 1182, 1095,
913 cmꢂ1 1H NMR (400 MHz, CDCl3):
; d 5.36 (br s, 1H), 4.18 (q,
J¼7.2 Hz, 4H), 2.43 (s, 2H), 2.09–2.07 (m, 4H), 1.70 (s, 3H), 1.25 (t,
J¼7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d 171.9, 131.5, 120.1, 61.4,
53.8, 35.2, 27.3, 23.7, 22.6, 14.3; MS (EI) m/z (%): 240 (15), 195 (9),
166 (44), 137 (18), 93 (100); HRMS (EI) calcd for C13H20O4
[M]þ¼240.1362, found 240.1361.
4.5.3. 3-Methyl-N-tosyl-2,5-dihydro-1H-pyrrole (Table 1, Entry
3). The representative procedure was followed using N-allyl-4-
methyl-N-(2-methylallyl)benzenesulfonamide (27 mg, 0.10 mmol)
and catalyst 2 (8.0 mg, 0.002 mmol). Column chromatography on
silica gel (eluting with 5% EtOAc/hexanes) afforded the product as
a white solid (24 mg, 99%). The 1H NMR spectral data obtained was
in accord with data previously reported for this compound.15
1035, 995, 900, 864 cmꢂ1 1H NMR (400 MHz, CDCl3):
; d 5.83–5.73
(m, 1H), 5.02 (dd, J¼17.2, 1.6 Hz, 1H), 4.96 (dd, J¼10.4, 1.6 Hz, 1H),
4.86 (s, 1H), 4.74 (s, 1H), 4.21–4.16 (m, 4H), 2.73 (s, 2H), 1.98 (s, 4H),
1.66 (s, 3H), 1.26 (t, J¼7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d
171.7, 140.9, 137.8, 115.7, 115.1, 61.4, 56.9, 40.3, 31.6, 28.7, 23.4, 14.2;
MS (ESI): m/z 291 (MþNa), 269 (MþH); HRMS (ESI) calcd for
C15H24O4Na [MþNa]þ¼291.1572, found 291.1571.
4.5.4. 5-Methyl-N-tosyl-1,2,3,6-tetrahydropyridine (Table 1, Entry
4). The representative procedure was followed using N-(but-3-enyl)-
4-methyl-N-(2-methylallyl)benzenesulfonamide (28 mg, 0.10 mmol)
and catalyst 2 (8.0 mg, 0.002 mmol). Column chromatography on
silica gel (eluting with 6% EtOAc/hexanes) afforded the product as
4.7. 1-(3-(2-Methylallyloxy)pent-4-enyl)benzene
A solution of 5-phenylpent-1-en-3-ol20 (0.11 g, 0.68 mmol) in
THF (3 mL) was added to a stirred suspension of NaH (0.06 g,