Seven-Membered Cyclic Enol Ether Derivatives
J . Org. Chem., Vol. 62, No. 19, 1997 6629
Sch em e 5
Exp er im en ta l Section
Gen er a l P r oced u r es. Reactions were run in dried glass-
ware under a nitrogen atmosphere. THF was distilled from
sodium benzophenone ketyl prior to use. Flash column chro-
matography was carried out on silica gel (Wakogel C-300).
Ethyl 2-hexenoate (3c) and ethyl 4-methyl-2-pentenoate (3d )
were prepared from triethyl phosphonoacetate and the
corresponding aldehyde by the method of Marmor.10 1,1-
Diphenylphospholanium perchlorate (1) was prepared by the
reaction of tetraphenyldiphosphine with 1,4-dibromobutane11
-
followed by exchange of Br- into ClO4 with a saturated
aqueous NaClO4 solution. All other reagents were available
from commercial sources and were used without further
purification. 1H NMR and 13C NMR spectra were acquired
on a 90 MHz spectrometer using CDCl3 as the solvent.
Chemical shifts are reported in δ from TMS as the internal
standard. Mass spectra and HRMS were obtained using EI
ionization at 70 eV. Melting points are uncorrected.
Gen er a l P r oced u r e of th e Rea ction of Cyclic P h os-
p h on iu m Ylid e 2 w ith En oa tes 3a -e. A solution of phos-
phonium salt (2.00 g, 5.87 mmol) and potassium tert-butoxide
(0.66 g, 5.87 mmol) in dry THF (25 mL) was stirred at room
temperature for 1 h. A solution of enoates (5.87 mmol) in dry
THF (5 mL) was added dropwise to the mixture, and the
resulting solution was refluxed for 16 h (48 h for 4e). After
being cooled to room temperature, the mixture was quenched
with water and extracted with CH2Cl2 or CHCl3. The com-
bined organic layer was washed with water, dried over
Na2SO4, and concentrated under reduced pressure. The
residue was purified by flash column chromatography on silica
gel using AcOEt-CHCl3 (1/1) as an eluent.
37% yield (based on the acrylate) instead of a normal
Michael-intramolecular Wittig product 4f. The struc-
ture of the adduct was assigned to 15 on the basis of the
1H NMR, 13C NMR, and mass spectra. The adduct 15
was thought to be supplied from the intramolecular
Wittig reaction of an intermediate (14) which would be
generated by the repetition of the Michael addition of 2
to 3f and regeneration of the ylide. The Michael addition
of the cyclic phosphonium ylide to ethyl acrylate (3f)
would be faster than the intramolecular Wittig reaction
until the formation of the intermediate 14. The intramo-
lecular Wittig reaction from 14 giving 15 would then be
preferable to the addition due to the sterically crowded
circumstances around the ylide carbon atom in 14.
t r a n s-(4-E t h o x y -2-p h e n y l-4-c y c lo h e p t e n -1-y l)d i -
p h en ylp h osp h in e oxid e (4a ): 1.79 g (73%); white solid, mp
170-174 °C; 1H NMR δ 1.09 (t, J ) 7 Hz, 3H), 2.01-3.62 (m,
10H), 4.57 (brt, 1H), 6.94-7.89 (m, 15H); IR (KBr) 1655 (CdC),
1160 cm-1 (PdO); MS m/ z 416 (M+). Anal. Calcd for
C27H29O2P: C, 77.86; H, 7.02. Found: C, 77.84; H, 7.09.
t r a n s -(4-E t h o x y -2-m e t h y l-4-c y c lo h e p t e n -1-y l)d i -
p h en ylp h osp h in e oxid e (4b): 1.48 g (71%); white solid, mp
The enol ether derivatives 4a -d obtained from these
reactions were single products because in these 13C NMR
spectra peaks ascribed to other stereoisomers were not
detected (Table 1). However, the stereochemistry rel-
evant to the cis or trans configuration of two substituents
bonded to the cycloheptene ring was not determined
because all of them were gradually hydrolyzed and
changed into the corresponding ketones at room temper-
ature. Also, the stereochemistry was not clarified by
NOE measurements due to the flexibility of the cyclo-
heptene skeleton. However, comparison of the 13C NMR
for 4a with the previously reported cycloheptene deriva-
tive 161 which was later confirmed to have a trans
relationship on the basis of X-ray crystallography9
suggested that 4a has an analogous ring conformation
and a similar dihedral angle between the Ph2P(O) and
Ph groups to 16. The sp3 carbon atoms of the cyclohep-
tene ring had almost similar chemical shifts and coupling
constants (J PC) to them in 16. Also, each ipso carbon
atom of the phenyl group adjacent to the Ph2P(O) group
of 4a and 16 was observed as a couple of doublet peaks
which had almost the same chemical shift and coupling
constant, 145.4 ppm (4.3 Hz) for 4a and 145.6 ppm (3.4
Hz) for 16. Moreover, the intramolecular Wittig reaction
was considered to proceed via a similar rigid phosphabi-
cycle for the reaction using acyclic and cyclic enones.1,2
Accordingly, it was also suggested from the reaction
mechanism that trans enol ether derivatives were pre-
dominantly formed.
1
157.7-158 °C; H NMR δ 0.98 (d, J ) 7 Hz, 3H), 1.22 (t, J )
7 Hz, 3H), 1.47-2.68 (m, 7H), 3.09 (brd, 1H), 3.57 (q, J ) 7 Hz,
2H), 4.51 (brs, 1H), 7.23-7.97 (m, 10H); IR (KBr) 1660 (CdC),
1175 cm-1 (PdO); MS m/ z 354 (M+). Anal. Calcd for
C22H27O2P: C, 74.55; H, 7.68. Found: C, 74.29; H, 7.69.
t r a n s -(4-E t h o x y -2-p r o p y l-4-c y c lo h e p t e n -1-y l)d i -
p h en ylp h osp h in e oxid e (4c): 1.23 g (55%); white solid, mp
1
124-129 °C; H NMR δ 0.58-2.65 (m, 19H), 3.15 (brd, 1H),
3.57 (q, J ) 7 Hz, 2H), 4.53 (brs, 1H), 7.26-8.02 (m, 10H); IR
(KBr) 1665 (CdC), 1180 cm-1 (PdO); MS m/ z 382 (M+). Anal.
Calcd for C24H31O2P: C, 75.37; H, 8.17. Found: C, 75.43; H,
8.25.
t r a n s-(4-E t h oxy-2-isop r op yl-4-cycloh e p t e n -1-yl)d i-
p h en ylp h osp h in e oxid e (4d ): 1.41 g (63%); white solid, mp
149-153 °C; 1H NMR δ 0.75 (d, J ) 6 Hz), 0.81 (d, J ) 6 Hz)
(total 6H), 1.20 (t, J ) 7 Hz, 3H), 1.47-2.80 (m, 8H), 3.25 (brd,
1H), 3.56 (q, J ) 7 Hz, 2H), 4.55 (brs, 1H), 7.25-8.01 (m, 10H);
IR (KBr) 1665 (CdC), 1180 cm-1 (PdO); MS m/ z 382 (M+);
HRMS calcd for C24H31O2P 382.2060, found 382.2064.
tr a n s-(4-E t h oxy-2,2-d im et h yl-4-cycloh ep t en -1-yl)d i-
p h en ylp h osp h in e oxid e (4e): 0.80 g (37%); white solid, mp
134-135 °C; 1H NMR δ 0.94 (s, 3H), 1.16 (s), 1.24(t, J ) 7 Hz)
(total 6H), 1.60-2.76 (m, 7H), 3.61 (q, J ) 7 Hz, 2H), 4.49
(brt, 1H), 7.30-8.00 (m, 10H); IR (KBr) 1660 (CdC), 1180 cm-1
(PdO); MS m/ z 368 (M+). Anal. Calcd for C23H29O2P: C,
74.98; H, 7.93. Found: C, 75.03; H, 7.95. (2,2-Dimethyl-4-
oxocycloheptyl)diphenylphosphine oxide (5), (7-methyl-5-oxo-
6-octenyl)diphenylphosphine oxide (6), and ethyl diphenylphos-
phinate (7) were also obtained. 5: 0.13 g (7%); white solid,
In conclusion, the reaction of the cyclic phosphonium
ylide 2 with enoates provided the seven-membered cyclic
enol ether derivatives with high stereoselectivity via the
tandem Michael-intramolecular Wittig reaction. In
addition, a novel reaction course was determined for the
reaction using ethyl acrylate and ethyl benzoate.
1
mp 196-198 °C; H NMR δ 1.04 (s), 1.12 (s) (total 6H), 1.32-
(10) Marmor, R. S. J . Org. Chem. 1972, 37, 2901-2904.
(11) (a) Purdum, W. R.; Berlin, K. D. J . Org. Chem. 1975, 40, 2801-
2806. (b) Marsi, K. L.; Lynch, D. M.; Hormer, G. D. J . Heterocycl. Chem.
1972, 9, 331-334. (c) Ma¨rkl, G. Angew. Chem., Int. Ed. Engl. 1963, 2,
620.
(9) Unpublished data.