2592 J . Org. Chem., Vol. 62, No. 8, 1997
Reynolds and Finn
phosphonium salt at -30 °C as above. The phosphonium salt
was isolated as a white powder after filtration, washing with
hexane, and drying under vacuum (1.905 g, 73%). 1H NMR
(CDCl3, δ) 7.73 (br s, 2H), 7.62-7.49 (m, 2H), 4.56 (q, J ) 6.0
Hz, 1H), 3.29 (s, 3H), 2.89 (d, 3J PH ) 4.2 Hz, 6H), 2.92 (d, 3J PH
water (75 mL). The mixture was extracted with Et2O (3
100 mL), and the combined organic layers were washed with
brine, dried over anhydrous Na2SO4, and reduced by rotary
evaporation to provide trans-2-phenyl-1-cyclopropanemethanol
(1.96 g, 13.2 mmol, 85%) as a pale yellow oil. 1H NMR (CDCl3,
δ) 7.36-7.14 (m, 5H), 3.63 (d, J ) 6.6 Hz, 2H), 3.33 (br s, 1H),
2
) 3.9 Hz, 6H), 2.52 (d, J PH ) 12.9 Hz, 3H), 1.45 (d, J ) 6.0
Hz, 3H); 13C NMR (CD3CN, δ) 148.0 (d, 2J PC ) 11.3 Hz), 134.8,
1.89-1.84 (m, 1H), 1.54-1.44 (m, 1H), 1.04-0.95 (m, 2H); 13
C
2
3
133.2 (d, J PC ) 11.5 Hz), 128.5 (d, J PC ) 7.0 Hz), 128.3 (d,
NMR (CDCl3, δ) 143.2, 128.9, 126.4, 126.1, 66.6, 25.7, 21.8,
14.5. To a stirred slurry of pyridinium chlorochromate (4.23
g, 19.6 mmol) in 150 mL of CH2Cl2 was added trans-2-phenyl-
1-cyclopropanemethanol (1.96 g, 13.2 mmol) in 10 mL of CH2-
Cl2. The reaction mixture was stirred for 1 h at room
temperature, during which time the color changed to very dark
brown and a sticky brown precipitate was observed. The liquid
in the flask was decanted and concentrated by rotary evapora-
tion and the resulting crimson oil purified by passage over a
short silica column eluting with THF. Evaporation of the
solvent provided 26 (1.671 g, 11.44 mmol, 86%) as a colorless
crystalline solid. 1H NMR (CDCl3, δ) 9.35 (d, J ) 4.5 Hz, 1H),
7.34-7.25 (m, 3H), 7.14 (d, J ) 7.2 Hz, 2H), 2.63 (m, 1H), 2.18
(m, 1H), 1.75 (m, 1H), 1.52 (m, 1H); 13C NMR (CDCl3, δ) 200.1,
139.4, 129.0, 127.3, 126.7, 34.2, 27.0, 16.9.
27. o-Phthalaldehyde (3.187, 23.78), (R,R)-(+)-1,2-diphenyl-
1,2-ethanediol (stilbenediol, 5.45 g, 25.5 mmol), and a catalytic
amount of p-toluenesulfonic acid were combined in benzene
and heated at reflux using a Dean-Stark trap. After ap-
proximately 3 h, the reaction was allowed to cool, washed with
water, and dried over Na2SO4. Evaporation of the solvent
provided 27 as a viscous yellow oil (6.7 g, 78%), which NMR
showed to be the result of clean monoprotection. However,
samples of this aldehyde were purified by silica gel chroma-
tography before use. 1H NMR (CDCl3, δ) 8.00 (br d, J ) 7.8
Hz, 1H), 7.71 (td, J ) 7.5 Hz, 1.5 Hz, 1H), 7.59 (td, J ) 7.5,
1.1 Hz, 1H), 7.36-7.31 (m, 11H), 7.07 (s, 1H), 5.04 (d, J ) 7.8
Hz, 1H), 4.96 (d, J ) 7.8 Hz, 1H); 13C NMR, (CDCl3, δ) 192.3,
139.8, 138.4, 136.6, 134.9, 134.4, 131.0, 130.1, 129.2, 128.9,
127.4, 126.9. 102.0, 87.9, 85.8.
3J PC ) 5.2 Hz), 119.9 (d, J PC ) 115.8 Hz), 74.3 (d, J PC ) 2.8
1
3
3
1
Hz), 55.4, 36.7 (d, J PC ) 3.3 Hz), 21.6, 12.7 (d, J PC ) 90.9
Hz); 31P NMR (CD3CN, δ) 60.7; IR (CH2Cl2, cm-1) 3033, 2950,
2821, 1477, 1302, 1173, 1110, 1098, 997 (s), 898; UV-vis (CH2-
Cl2) 230, 248; [R]298 -29.7 (c ) 10.7, CH2Cl2); mp 180-182
D
°C.
Asym m etr ic Syn th esis of Allen es (Sch em e 7). Phos-
phonium salt 21 (0.240 g, 0.427 mmol) was stirred with 1 equiv
of NaN(SiMe3)2 (0.386 g of a 1.106 mmol/g of solution in THF)
in 30 mL of THF for 10 min. The resulting dark golden-orange
ylide solution was added to a solution of TiCl3OiPr (91 mg,
0.43 mmol in 5 mL of hexane), forming a cloudy dark
red-orange mixture, which was then treated with equiv of
NaN(SiMe3)2 in THF. The metalated ylide mixture was
divided into two equal portions, and each was treated with
8.8 equiv of aldehyde (benzaldehyde, 200 mg, 1.89 mmol;
4-methylbenzaldehyde, 230 mg, 1.92 mmol), causing an im-
mediate color change to yellow. After standing overnight, each
reaction mixture was reduced by rotary evaporation, and the
resulting sticky solid dissolved in a minimal amount of CH2-
Cl2 for silica gel chromatography (10% CH2Cl2 in petroleum
ether) to yield 23 (6.7 mg, 16.3%) and 12 (12.5 mg, 27%),
respectively. For 23, [R]298 -110.4° (c ) 0.6, toluene); M298
D
D
) -211.9°. Optical purity was determined by comparison with
the literature:20 (211.9/1958) 100 ) 10.8%, enriched in the
R-isomer as shown in Scheme 7. For 12, [R]298 -118.2° (c )
D
1.5, toluene); M298D ) 260.0°. If one assumes that the p-methyl
substituents do not make the optical rotation of 12 significantly
different from that of 23, then the optical purity of 12 is
approximately 13%, again favoring the R configuration. Phos-
phonium salt 22 was used in exactly the same procedure,
Gen er a l P r oced u r e for Obser va tion of Oxa p h osp h e-
ta n e Dia ster eom er s (F igu r e 8). A solution of [(Me2N)3P13
-
yielding allene 12 in 20% yield with an optical rotation of M298
CHdCH-C6H4CH3]BPh4 (13a ) in THF was treated with 2 equiv
of phenyllithium at -78 °C. To the solution of deprotonated
vinylphosphonium was added the desired aldehyde as a chilled
(-78 °C) solution in THF. Upon addition of the aldehyde, an
immediate color change from yellow to colorless was observed.
Aliquots of this solution were transferred by cannula into cold
(liquid N2 chilled) screw-cap NMR tubes under positive N2
pressure, which were stored at -78 °C for up to 2 h before
low-temperature NMR analysis. In general, diastereomers
were more distinguishable by 13C NMR than by 31P NMR. For
the oxaphosphetane 28 derived from 25: 13C NMR (THF, δ)
155.0 (d, 1J CP ) 163.5 Hz), 154.2 (d, 1J CP ) 160.2 Hz). For the
oxaphosphetane derived from 26: 13C NMR (THF, δ) 156.6 (d,
D
) -200.0°, indicating an optical purity of approximately 10%,
enriched in the R enantiomer.
25. Under inert atmosphere, a solution of 2-bromobenzal-
dehyde (2.9 g, 15.7 mmol) in dry Et2O at -78 °C was treated
with methyllithium (11.0 mL, 1.4 mmol/mL; 15.4 mmol) by
cannula. The solution foamed vigorously and a light pink color
developed. After stirring for 3 min, the reaction mixture was
added to a slurry of ice in 1 M HCl. The organic layer was
separated, and dried over Na2SO4, and the solvent was
removed by rotary evaporation to afford racemic 2-bromo-R-
methylbenzyl alcohol (1.91 g, 9.5 mmol, 61%), with the 1H
NMR spectrum matching that of the commercially available
(S)-(-)-enantiomer. Conversion to the methyl ether was
accomplished as described above for the synthesis of 22.
2-Bromo-R-methylbenzyl methyl ether (0.786 g, 3.65 mmol)
in 40 mL of anhydrous ether was cooled to -78 °C, treated
with 2 equiv of t-BuLi (4.0 mL, 1.7 M solution), and stirred
for 15 min. To the resulting pale yellow solution was added
neat N-formylpiperidine (0.712 g, 6.3 mmol) by syringe, and
the reaction mixture was allowed to warm to room tempera-
ture over 1 h. The reaction was quenched with 75 mL of 3 M
HCl and extracted with ether (3 75 mL), and the combined
organic layers were washed with NaHCO3 (150 mL) and brine
(150 mL) before drying over Na2SO4. Rotary evaporation,
followed by drying under vacuum, yielded aldehyde 25 as a
yellow oil (0.410 g, 2.5 mmol, 68%). 1H NMR (CDCl3, δ) 10.28
(s, 1H), 7.82 (d, J ) 7.5, 1H), 7.62-7.59 (m, 2H), 7.43 (t, J )
6.9 Hz, 1H), 5.19 (q, J ) 6.6 Hz, 1H), 3.23 (s, 3H), 1.44 (d, J )
6.6 Hz, 3H); 13C NMR (CDCl3, δ) 193.3, 147.0, 134.5, 133.8,
133.4, 127.9, 126.9, 76.2, 57.2, 24.3.
1
1J CP ) 157.7 Hz), 155.8 (d, J CP ) 157.6 Hz); 31P NMR (THF,
1
1
δ) -18.8 (d, J CP ) 158.50 Hz), 19.3 (d, J CP ) 154.3 Hz); for
the oxaphosphetane derived from 27: 13C NMR (THF, δ) 154.7
(d, 1J CP ) 164.0 Hz), 154.2 (d, 1J CP ) 160.4 Hz); 31P NMR (THF,
1
1
δ) -17.7 (d, J CP ) 151.5 Hz), -18.0 (d, J CP ) 167.4 Hz).
The NMR tubes were warmed to 25 °C and allowed to stand
for several hours before diastereomer ratios were obtained by
13C NMR of the central (labeled) allene carbon. In the case of
the allene derived from 27, these 13C peaks were found to be
coincident, so the allene was isolated and the diastereomer
ratio determined by comparison of other resonances (see
below). The solutions from which the NMR aliquots were
removed were allowed to warm to room temperature overnight.
The solvent was removed by rotary evaporation and the
residue purified by flash chromatography, taking care to avoid
separation of diastereomers, to provide the allenes described
below.
30. From vinylphosphonium salt 13a -13C1 (0.109 g, 0.182
mmol), PhLi (40 mg, 0.48 mmol), and aldehyde 25 (0.166 g,
1.01 mmol), allene 30 was isolated (27 mg, 0.102 mmol, 56%)
as a mixture of diastereomers. 1H NMR (CDCl3, δ, asterisks
mark resonances of the major diastereomer): 7.46-7.41 (m,
2H), 7.27-7.20 (m, 3H), 7.14 (d, J ) 7.5 Hz, 2H), *6.94 (d, J
) 6.6 Hz, 1H), 6.93 (d, J ) 6.3 Hz, 1H) 6.55 (m, uneven triplet),
26. To a vigorously stirred solution of trans-2-phenyl-1-
cyclopropanecarboxylic acid (2.536 g, 15.7 mmol) in 100 mL
of THF at 0 °C was added solid LiAlH4 (1.911 g, 48.7 mmol)
in small portions over 40 min. The reaction mixture was
stirred for 90 min and was then quenched by the cautious
addition of water (75 mL), 10% aqueous NaOH (50 mL), and