7738 J . Org. Chem., Vol. 65, No. 23, 2000
Shumway et al.
were obtained in CDCl3 at 300 MHz 1H and 75 MHz (13C)
unless otherwise indicated. Chemical shifts are reported in
ppm, couplings in Hz. HPLC separations were performed using
an absorbance detector at 260 nm, and a 19 mm × 30 cm 60
Å, 60 µm silica gel column.
receiving end of the quartz tube used with liquid nitrogen as
the trapping agent. An addition funnel was placed on the top
of the quartz tube and used for sample delivery into the heated
tube. The apparatus was evacuated by a rough pump that
provided approximately 0.25 Torr vacuum. In each experiment
the vacuum and tube furnace were allowed at least 2 h to
equilibrate before samples were introduced. After each experi-
ment the apparatus was filled with helium, the tube furnace
cooled, and the trap warmed to room temperature. Reported
selectivities were reproduced in at least two experiments.
6-Meth yl-2-(1-ph en yleth yl)-4H-1,3-dioxin -4-on e (4a, 5a).
A mixture of 2-phenyl-3-propanal (3a ) (2.03 mL, 15.4 mmol),
2 (1.0 mL, 7.7 mmol), and dichloromethane (2 mL) was
subjected to FVT conditions. The resultant liquid was ro-
tovapped and the ratio of diastereomers determined by NMR
to be 2.3:1. The products were purified by silica gel chroma-
tography (hexane/EtOAc, 24/1, 250 mL, hexane/EtOAc, 95/5,
400 mL), giving a 40% combined yield. Separation of the
diastereomers was accomplished by successive HPLC (hexane/
EtOAc, 95/5).
3-P h en yl-2-bu ta n ol. In a 100 mL round-bottom flask, THF
(20 mL) and 2-phenylpropanal (1.8 mL, 14.9 mmol) were cooled
to -78 °C. To this reaction mixture methyllithium solution
(10.0 mL, 16.4 mmol, 1.4 M) was slowly added. After complete
addition the reaction was warmed to room temperature. The
reaction was worked up in ether then washed successively with
sodium bicarbonate and brine solutions: 99% yield.43
3-P h en yl-2-bu ta n on e (3b). In a 100 mL round-bottom
flask with dichloromethane (20 mL) and DMSO (2.50 mL, 25.6
mmol) were cooled to -78 °C. Oxalyl chloride (1.70 mL, 19.2
mmol) was added and allowed to stir for 30 min. To this
solution a mixture of 3-phenyl-2-butanol (1.90 mL, 12.8 mmol)
and dichlormethane (5 mL) was added and allowed to stir for
30 min. To this reaction mixture Et3N (8.9 mL, 64 mmol) was
added, allowed to stir 10 min and then warmed to room
temperature. This Swern oxidation was worked up in ether
and washed with sodium bicarbonate and brine solutions.
Evaporation of solvent followed by silica gel chromatography
(Hexane/EtOAc, 95/5, 200 mL) gave 3b in 58% yield.44
2-P h en yl-3-p en ta n ol. In a 100 mL round-bottom flask
fitted with a reflux condenser magnesium turnings (0.38 g,
12.2 mmol), THF (20 mL), and bromoethane (1.14 mL, 15.3
mmol) were added and stirred. After 2 h the consumption of
magnesium stopped and the reaction cooled indication comple-
tion of reaction. The resultant Grignard was transferred slowly
via cannula to a 250 mL three neck flask fitted with a reflux
condenser and containing THF (20 mL) and 2-phenylpropanal
(1.61 mL, 12.2 mmol). The reaction was monitored by TLC and
worked up after 2 h by extraction with ether and washed with
sodium bicarbonate and brine solutions. Evaporation of solvent
followed by silica gel chromatography (hexane/EtOAc, 95/5,
500 mL) gave a 36% yield.45
2-P h en yl-3-p en ta n on e (3c). The procedure for the prepa-
ration of 3b was followed, using 0.69 mL of DMSO (7.6 mmol),
0.50 mL of oxalyl chloride (5.7 mmol), 0.63 g of 2- phenyl-3-
pentanol (3.8 mmol), and 2.65 mL of Et3N (19.0 mmol).
Purification by silica gel chromatography (hexane/EtOAc, 9/1,
100 mL, then hexane/EtOAc, 8/2, 100 mL) gave 3c in 80%
yield.46
2,2-Dim eth yl-4-p h en yl-3-p en ta n ol. In a 100 mL round-
bottom flask, hexane (25 mL), diethyl ether (15 mL) and
2-phenylpropanal (1.4 mL, 10.4 mmol) were cooled to -5 °C
and tert-butyllithium (12.3 mL, 20.9 mmol, 1.7 M) was added
slowly. The reaction was allowed to stir 30 min and monitored
by TLC. The reaction was worked up in ether and washed with
sodium bicarbonate and brine solutions. Evaporation of the
solvent followed by silica gel chromatography (hexane/EtOAc,
9/1, 200 mL, hexane/EtOac, 8/2, 200 mL) produced a mixture
of the two diastereomers in 50% yield.47
4a : 1H NMR (200 MHz) 1.46 (d, 3H, J ) 7.2 Hz), 1.97 (s,
3H), 3.30 (dq, 1H), 5.26 (s, 1H), 5.50 (d, 1H, J ) 5.0), 7.32 (m,
5H); 13C NMR (50 MHz) 14.90, 19.34, 42.78, 95.94, 102.92,
127.26, 128.42, 128.47, 139.55, 162.54, 172.02. Anal. Calcd
C
13H14O3; C, 71.54; H, 6.47. Found; C, 71.24; H, 6.38.
5a : 1H NMR (200 MHz) 1.46 (d, 3H, J ) 7.2 Hz), 1.97 (s,
3H), 3.30 (dq, 1H), 5.26 (s, 1H), 5.50 (d, 1H, J ) 5.0), 7.32 (m,
5H); 13C NMR (50 MHz) 14.42, 19.34, 42.63, 95.94, 102.80,
127.26, 128.42, 128.47, 139.55, 162.54, 172.02.
2,6-Dim eth yl-2-(1-ph en yleth yl)-4H-1,3-dioxin -4-on e (4b,
5b). A mixture of 3-phenyl-2-butanone (3b, 1.08 g, 7.4 mmol),
2 (0.97 mL, 7.4 mmol) and dichloromethane (2 mL) were
subjected to FVT conditions. The resultant liquid was ro-
tovaped and the ratio of diastereomers determined by NMR
to be 6.4:1. The products were purified by silica gel chroma-
tography (hexane/EtOAc, 98/2, 200 mL, hexane/EtOAc, 95/5,
400 mL) giving an 11% combined yield/Separation of diaste-
riomers was accomplished by HPLC (hexane/EtOAc, 95/5). A
crystal structure of 5b was obtained by X-ray diffraction.
1
4b: H NMR (200 MHz) 1.44 (d, 3H, J ) 7.23 Hz), 1.48 (s,
3H), 1.96 (s, 3H), 3.30 (q, 1H, J ) 7.13 Hz), 5.20 (s, 1H), 7.27
(m, 5H); 13C NMR (50 MHz) 15.4, 19.9, 20.6, 47.5, 93.7, 109.3,
116.4, 122.2, 128.2, 129.1, 140.7, 160.9, 168.6. Anal. Calcd for
C
14H16O3: C, 72.39; H, 6.94. Found: C, 72.42; H, 7.05.
5b: H NMR (200 MHz) 1.44 (d, 3H, J ) 7.13 Hz), 1.49 (s,
1
3H), 1.96 (s, 3H), 3.25 (q, 1H, j ) 7.12 Hz), 5.18 (s, 1H), 7.27
(m, 5H); 13C NMR (50 MHz) 15.4, 19.9, 20.9, 47.9, 93.8, 109.1,
127.2, 128.2, 129.1, 140.2, 161.0, 168.5.
2-E t h yl-6-m et h yl-2-(1-p h en ylet h yl)-4H -1,3-d ioxin -4-
on e (4c, 5c). A mixture of 2-phenyl-3-pentanone (3c, 1.02 g,
5.8 mmol), 2 (0.82 mL, 5.8 mmol), and dichloromethane (3.0
mL) was subjected to FVT conditions. The resultant liquid was
rotovapped and the ratio of diastereomers determined by NMR
to be 2:1. The products were purified by silica gel chromatog-
raphy (hexane/EtOAc, 24/1, 250 mL, hexane/EtOAc, 95/5, 200
mL) giving a combined yield of 5.4% for 4c and 5c. Further
separation of diasteriomers was accomplished by HPLC (hex-
ane/EtOAc, 95/5).
2,2-Dim eth yl-4-p h en yl-3-p en ta n on e (3d ). The procedure
for the preparation of 3b was followed, using 0.37 mL of DMSO
(4.0 mmol), 0.32 mL of oxalyl chloride (3.6 mmol), 0.39 g of
2,2-dimethyl-4-phenyl-3-pentanol (2.0 mmol), and 1.42 mL of
Et3N (10.0 mmol). Purification by silica gel chromatography
(hexane/EtOAc, 95/5, 100 mL) gave a 57% yield.47
F la sh Va cu u m Th er m olysis (F VT). All FVT experiments
were carried out in the following manner unless otherwise
noted. A quartz tube approximately 50 cm in length was placed
vertically and heated by a tube furnace to approximately 400
°C as measured with a thermocouple. A trap placed at the
1
4c: H NMR 0.89 (t, 3H, J ) 7.5 Hz), 1.40 (d, 3H, J ) 7.2
Hz), 1.66 (m, 1H), 1.97 (s, 3H), 2.06 (m, 1H), 3.42 (q, 1H, J )
7.1 Hz), 5.14 (s, 1H), 7.26 (m, 5H); 13C NMR 7.3, 15.6, 19.9,
26.4, 44.9, 93.4, 111.5, 127.1, 128.3, 129.0, 140.3, 163 (tentative
assignment), 168.5.
1
5c: H NMR 0.92 (t, 3H, J ) 7.2 Hz), 1.40 (d, 3H, J ) 7.2
Hz), 1.67 (m, 1H), 1.94 (s, 3H), 2.0 (m, 1H), 3.37 (q, 1H, J )
7.1 Hz), 5.07 (s, 1H), 7.26 (m, 5H); 13C NMR 7.3 15.5, 19.9,
26.9, 45.2, 93.4, 111.3, 127.1, 128.2, 129.2, 140.2, 161 (tentative
assignment), 168.4.
(43) Kingsbury, C. A.; Thorton, W. B. J . Org. Chem. 1996, 31, 1000-
1004.
1-(1-P h en yleth yl)-1-p r op en yl 3-oxobu ta n oic Ester (9).
This was formed in 24% yield in the reaction that formed 4c
and 5c. Final purification was done by HPLC (hexane/Et2O,
3/1); this failed to separate the cis and trans isomers. The NMR
spectrum shows keto-enol tautomers of both isomers: 1H
NMR (d, 3H, J ) 6.2), 1.19 (d, 0.7H, J ) 6.2), 1.28 (d, 3.7H, J
) 6.3), 2.0 (s, 0.6H), 2.22 (s, 3H), 2.85 (m, 1.4H), 3.26 (s 0.4H),
(44) Aranda, A.; Diaz, A.; Diez-Barra, E.; de la Hoz, A.; Moreno, A.;
Sanchez-Verdu, P. J . Chem. Soc., Perkin Trans 1. 1992, 2427.
(45) J ones, P.; Goller, E. J .; Kauffman, W. J . J . Org. Chem. 1971,
36, 1-3315.
(46) Rathke, M. W.; Vigiazoglou, D. J . Org. Chem. 1987, 52, 3697-
3698.
(47) Zioudrou, C.; Moastakali-Mavridis, M.; Chrysuchou, P.; Kura-
batsos, G. J . Tetrahedron 1978, 34, 3181-3186.