Waddell et al.
substitution results in a complete lack of C2-C7 cyclization,
which has been previously noted to be more sensitive to steric
influences than the competing C2-C6 cyclization. When the
alkynyl substituent is changed from TMS to phenyl, the resulting
relief of steric strain in the C2-C7 transition state permits C2-
C7 cyclization to occur at cryogenic temperature. The higher
yield and faster reaction in the cyclohexannulated system can
possibly be attributed to a lower degree of ring strain encoun-
tered in the C2-C7 transition state.
Although our results are mostly in agreement with those of
Schmittel et al.,2f we note that whereas Schmittel found exclusive
C2-C6 cyclization for his cyclohexannulated systems, we
observe the thermal C2-C6 cyclization of the bis-TMS system
3 and the cryogenic C2-C7 cyclization of the mixed TMS/
phenyl-substituted enyne-allene 33b. The anomalous C2-C7
cyclization of 33b can be explained by the greater steric demand
of the TMS substituents used in our study, resulting in the
destabilization of the C2-C7 pathway. It is also noteworthy that
the cyclizations of oxyanion-substituted enyne-allenes in our
study occur at far lower temperatures than the analogous
cyclizations of neutral enyne-allenes. The presence of the
oxyanion presumably lowers the activation energy of both
cyclization pathways by resonance stabilization by the oxyanion
of the incipient diradicals in the transition states of these
cyclizations. The C2-C7 cyclization of 33a represents one of
the fastest examples of a Myers-Saito cycloaromatization ever
reported.9
SO4 and purified by flash chromatography with 25% EtOAc-
petroleum ether, affording 11 as a pale yellow liquid (0.16 g, 80%
yield): 1H NMR (300 MHz, CDCl3) δ 3.80 (s, 3H), 2.70 (t, 2H, J
) 5.3 Hz), 2.60 (t, 2H, J ) 5.3 Hz), 2.00 (m, 2H), 0.20 (s, 9H);
13C NMR (75 MHz, CDCl3) δ 143.0, 125.1, 101.5, 100.0, 61.4,
37.7, 35.0, 22.8, 0.0; IR (NaCl, cm-1) 2984, 2086, 1741, 1240,
1047, 847, 634; HRMS m/z (EI/CI) expected 251.1342, found
251.1344.
1-(2-Trimethylsilylacetylenylcyclopent-1-enyl)-3-trimethylsi-
lylpropyn-1-one (12). To a solution of BuLi as a 1.6 M solution
in hexanes (5.8 mL) in THF (8 mL) at -78 °C was added
trimethylsilylacetylene (1.60 mL, 11.1 mmol), and the mixture was
stirred for 20 min. To this solution was added acetylated amide 11
(0.93 g, 3.7 mmol) in THF (4.3 mL), and the mixture was stirred
for 30 min. The reaction was diluted with Et2O and poured into
saturated, aqueous NH4Cl. The aqueous phase was separated and
extracted with Et2O (3×). The combined organic layer was dried
over Na2SO4 and purified by flash chromatography with 5% Et2O-
petroleum ether to give a colorless liquid 12 (0.85 g, 80%(: 1H
NMR (300 MHz, CDCl3) δ 2.80 (m, 4H), 1.9 (m, 2H) 0.27 (s,
9H), 0.25 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 173.9, 145.9,
136.1, 109.1, 102.7, 100.9, 99.8, 40.9, 33.6, 22.3, 0.06, 0.05; IR
(NaCl, cm-1) 2985, 2086, 1740, 1373, 1240, 1046, 737; HRMS
m/z (EI/CI) expected 288.1366, found 288.1370.
1-(2-Phenylacetylenylcyclopent-1-enyl)-3-phenylbuta-1,2-di-
enyl Acetate (17). CuI (0.26 g, 1.35 mmol) was suspended in Et2O
(1.0 mL) and cooled to 0 °C. To this suspension was added MeLi
(1.7 mL, 1.4 M in Et2O, 2.4 mmol). The solution was stirred for 5
min and cooled to -78 °C. A solution of ketone 16 (0.20 g, 0.68
mmol) dissolved in Et2O (1.0 mL) was added dropwise via syringe
to the reaction, which immediately turned dark red-orange. Acetic
anhydride (0.13 mL) in Et2O (0.2 mL) was then added dropwise
to the reaction, which was allowed to slowly warm to room
temperature over 1 h. The reaction was diluted with Et2O and
poured into saturated, aqueous NH4Cl and extracted with Et2O (3×).
The combined organic layer was dried over Na2SO4 and purified
by flash chromatography with 10% Et2O-petroleum ether to give
17 as a pale yellow liquid (0.16 g, 67%): 1H NMR (300 MHz,
CDCl3) δ 7.3-7.7 (m, 10H), 2.8 (m, 2H), 2.6 (m, 2H), 2.3 (s, 3H),
2.2 (s, 3H), 2.0 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 200.4,
169.3, 138.5, 137.9, 135.4, 131.4, 129.1, 128.6, 128.4, 128.3, 128.2,
126.8, 125.4, 123.7, 122.2, 119.7, 112.2, 39.7, 34.2, 21.1, 17.9; IR
(NaCl, cm-1) 2956, 2200, 1759, 1491, 1206; HRMS m/z (EI/CI)
expected 354.1620, found 354.1623.
1-(2-Phenylacetylenylcyclopent-1-enyl)-3-trimethylsilylpropyn-
1-one (22). To a solution of 21 (0.13 g, 0.46 mmol) in CH2Cl2
(4.5 mL) was added activated MnO2 (0.91 g, 10 mmol) and the
mixture was stirred for 12 h. The reaction mixture was filtered over
Celite, concentrated under reduced pressure, and purified by flash
chromatography with 10% Et2O-pentane to give 22 as a pale
yellow liquid (0.102 g, 77%): 1H NMR (300 MHz, CDCl3) δ 7.4
(m, 2H), 7.2 (m, 3H), 2.75 (m, 4H), 1.8 (q, 2H, J ) 7.6 Hz), 0.0
(s, 9H); 13C NMR (75 MHz, CDCl3) δ 173.9, 146.0, 137.2, 131.8,
129.1, 128.4, 122.8, 102.5, 102.3, 99.9, 85.6, 40.6, 33.0, 21.9, -0.7;
IR (NaCl, cm-1) 3123, 2948, 2916, 2852, 2191, 2151, 1599, 1492,
1448, 1401, 1357, 1250; HRMS m/z (EI/CI) expected 292.1283,
found 292.1290.
Experimental Section
2-Bromocyclopent-1-ene-N-methoxy-N-methylcarboxamide
(10). To a solution of carboxylic acid 9 (1.55 g, 8.10 mmol) in
CH2Cl2 (27 mL) was added (COCl)2 (1.42 mL, 16.2 mmol),
followed by catalytic DMF (50 µL). The reaction was stirred at
room temperature for 1 h, at which time the solution was
concentrated in vacuo with minimal exposure to air. The crude acid
chloride was redissolved in CH2Cl2 (27 mL) and cooled to 0 °C.
To this solution was added ClH2N(OMe)Me (0.87 g, 8.9 mmol),
followed by Hunig’s base (3.1 mL, 18 mmol). The mixture was
allowed to warm to room temperature over 4 h. The reaction mixture
was diluted with EtOAc and poured into 0.1 M HCl. The aqueous
layer was extracted with EtOAc (3×). The combined organic layer
was dried over Na2SO4 and purified by flash chromatography with
30% EtOAc-petroleum ether, affording 10 as a colorless foamy
solid (1.6 g, 100% yield): mp ) 60-62 °C; 1H NMR (300 MHz,
CDCl3) δ 3.70 (s, 3H), 2.70 (m, 4H), 2.10 (m, 2H); 13C NMR (75
MHz, CDCl3) δ 136.7, 121.0, 61.7, 40.7, 34.3, 22.7; IR (NaCl,
cm-1) 2960, 2928, 2254, 1631, 1387, 1260, 1097, 920, 760; HRMS
m/z (EI/CI) expected 233.0051, found 233.0056.
2-Trimethylsilylacetylenylcyclopent-1-ene-N-methoxy-N-me-
thylcarboxamide (11). To a solution of BuLi (0.90 mL, 2 M in
hexanes, 1.8 mmol) in THF (0.9 mL) at -78 °C was added
trimethylsilylacetylene (0.30 mL, 2.0 mmol), and the mixture was
stirred for 20 min. This mixture was added to a separate round-
bottom flask containing dry ZnBr2 (flame-dried under vacuum, 0.40
g, 1.8 mmol) in THF (0.9 mL) at -10 °C and stirred for 5 min. To
this solution was added Weinreb amide 10 (0.19 g, 0.80 mmol) in
THF (0.9 mL), followed by Pd(PPh3)4 (0.09 g, 0.08 mmol), and
the resulting reaction slowly warmed to room temperature over 3
h. The reaction was diluted with EtOAc and poured into saturated,
aqueous NH4Cl. The aqueous phase was separated and extracted
with EtOAc (3×). The combined organic layer was dried over Na2-
2,3-Dihydro-6-phenyl-5-(1-trimethylsilylvinyl)inden-4-ol (24).
To a solution of enyne-allenoate 23 (0.102 g, 0.29 mmol) dissolved
in PhCH3 (1.82 mL) at -10 °C was added MeLi as a 1.6 M solution
in Et2O (0.27 mL) dropwise, and the solution turned deep red-
orange. The reaction was allowed to stir at -10 °C for 3 h. The
reaction was diluted with Et2O and poured into saturated, aqueous
NH4Cl and extracted with Et2O (3×). The combined organic layer
was dried over Na2SO4 and purified by flash chromatography with
5% Et2O-petroleum ether to give 24 as a pale yellow liquid (0.013
g, 15%): 1H NMR (300 MHz, CDCl3) δ 7.4 (s, 5H), 7.0 (s, 1H),
6.0 (s, 1H), 5.3 (s, 1H), 4.7 (s, 1H), 2.8 (m, 2H), 2.5 (m, 2H), 2.1
(m, 2H), 0.2 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 151.3, 149.2,
(9) The cycloaromatization of didehydro[10]annulene is the fastest
reported example, occurring spontaneously at -45 °C: Myers, A. G.;
Finney, N. S. J. Am. Chem. Soc. 1992, 114, 10986-10987.
8376 J. Org. Chem., Vol. 71, No. 22, 2006