3-Unsubstituted 1,5-diaryl-2,4-pentanediones and -4-methoxy-2-pentanones: Synthesis via corresponding 3-hydroxy ketones generated from 2-isoxazolines

Article abstract of DOI:10.1021/jo960887a

Aryl acetaldoximes are reacted with allylarenes in the presence of sodium hypochlorite to give 3,5-bis(arylmethyl)-2-isoxazolines which are then converted to 1,5-diaryl-4-hydroxy-2-pentanones by a reductive hydrogenation in the presence of water. These in

Full text of DOI:10.1021/jo960887a

8604
J . Org. Chem. 1996, 61, 8604-8609
3-Un su bstitu ted 1,5-Dia r yl-2,4-p en ta n ed ion es a n d
-4-m eth oxy-2-p en ta n on es: Syn th esis via Cor r esp on d in g 3-Hyd r oxy
Keton es Gen er a ted fr om 2-Isoxa zolin es
J uha T. Pulkkinen* and J ouko J . Vepsa¨la¨inen
Department of Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland
Received May 14, 1996X
Aryl acetaldoximes are reacted with allylarenes in the presence of sodium hypochlorite to give
3,5-bis(arylmethyl)-2-isoxazolines which are then converted to 1,5-diaryl-4-hydroxy-2-pentanones
by a reductive hydrogenation in the presence of water. These intermediate aldols can then be
either oxidized with Corey-Kim reagent to stable dimethylsulfonium 1-(arylacetyl)-2-oxo-3-
arylpropylides followed by zinc-acetic acid reduction to give 1,5-diaryl-2,4-pentanediones, or
converted to 1,5-diaryl-4-methoxy-2-pentanones by refluxing in methanol in the presence of
hydrochloric acid. A detailed study of this general route is reported here.
1,3-Diketones are an important class of compounds
dipolar cycloaddition of acetylenic derivatives with nitrile
oxides to build up isoxazoles, which are then converted
to â-enamino ketones by reductive ring opening followed
by acidic hydrolysis to â-diketones.6 Nevertheless, this
method is rather limited because of the somewhat dif-
ficult accessibility of the acetylenic compounds,6c and the
idea of using it was therefore dismissed.
because of their high synthetic utility and ability to form
stable complexes. These enolizable compounds can act
as binding sites to both metal ions1 and nonmetallic
elements2 and are therefore used as subunits in su-
pramolecular host molecules.3 3-Unsubstituted 2,4-pen-
tanediones and 4-methoxy-2-pentanones with aromatic
groups at 1,5-positions have very flexible structures due
to negligible rotational barriers of the skeletal bonds.
Having a binding site for a cation, they could act, for
example, as templates in artificial allosteric systems.
Despite the simplicity of the title compounds, general
routes leading to them have not been reported yet. Only
a few papers describe synthesis of the diketones 7 with
two similar aromatic groups at the opposite ends of the
same molecule,4 and methods for the methoxy ketones 5
are previously unpublished.
There are mainly two straightforward approaches for
the synthesis of 1,3-diketones. The traditional way is an
acylation reaction of a methyl ketone with a carboxylic
acid derivative.5 However, in our case the methyl ketone
would have been an arylacetone which tends to undergo
acylation at the methylene rather than the methyl
group.5a This was also proved by our unsuccesful efforts
to make diketones 7 by an acylation using NaH or LDA
as the base. Even the kinetically controlled acylation of
the dianion of an arylacetone gave the same result.
Furthermore, we made several attempts to produce the
diketones from malonyl chloride and benzyllithium, from
dichloromethane and lithium salts of the ethylene dithi-
olane or ethylene acetal of phenyl acetaldehyde, and by
an acylation reaction of diethyl malonate with an aryl
acetyl chloride, but they also were unsuccessful. On the
other hand, 1,3-diketones can be prepared using a 1,3-
3-Methoxy ketones can be prepared via 3-hydroxy
ketones which also give an entry to the corresponding
1,3-diketones. The synthesis of 3-hydroxy ketones is
usually carried out either by using an aldol condensation
of carbonyl compounds with aldehydes7 or by preparing
an 2-isoxazoline6b,c,8 which can then be converted to the
corresponding aldol with a catalytic hydrogenation.9
Because the methylene carbon of the precursor ketone
is activated, the aldol condensation method would fail
in the present case for the same reason as the acylation
did. Therefore, we decided to use the second method.
We reported earlier a general route to the title com-
pounds10 which is based on using a nitrile oxide - olefin
[3 + 2] cycloaddition reaction to build up the five-carbon
skeleton of the molecules. The cycloaddition product, a
2-isoxazoline, is readily hydrogenated in the presence of
water to a 3-hydroxy ketone, which can be either oxidized
via stable dimethylsulfonium methylide to a 1,3-dike-
tone11 or converted to a 3-methoxy ketone with a one flask
synthesis (Scheme 1). We wish to report here a more
detailed study which, to the best of our knowledge, is the
first general route to the title compounds having different
aromatic groups and using the same precursor to produce
both the diketones 7 and the methoxy ketones 5.
(6) (a) Casnati, G.; Quilico, A.; Ricca, A.; Vita Finzi, P. Tetrahedron
Lett. 1966, 7, 233. (b) Bast, K.; Christl, M.; Huisgen, R.; Mack, W.;
Sustmann, R. Chem. Ber. 1973, 106, 3258. (c) Baraldi, P. G.; Barco,
A.; Benetti, S; Pollini, G. P.; Simoni, D. Synthesis 1987, 857. (d)
Bianchi, G.; De Amici, M. J . Chem. Soc., Chem. Commun. 1978, 962.
(7) (a) Nielsen, A. T.; Houlihan, W, J . Org. React. 1968, 16, 1. (b)
Mukaiyama, T. Org. React. 1982, 28, 203.
(8) (a) Lee, G. A. Synthesis 1982, 508. (b) Ko, S. S.; Confalone, P. N.
Tetrahedron 1985, 41, 3511. (c) Sugiyama, T. Appl. Organomet. Chem.
1995, 9, 399. (d) Mancera, M.; Roffe´, I.; Galbis, J . A. Tetrahedron 1995,
51, 6349.
X Abstract published in Advance ACS Abstracts, November 1, 1996.
(1) Bonati, F. Organomet. Chem. Rev. 1966, 1, 379.
(2) Pike, R. M. Coord. Chem. Rev. 1967, 2, 163.
(3) (a) Alberts, A. H.; Cram, D. J . J . Chem. Soc., Chem. Commun.
1976, 958. (b) Maverik, A. W.; Buckingham, S. C.; Yao, Q.; Bradbury,
J . R.; Stanldy, G. G. J . Am. Chem. Soc. 1986, 108, 7430. (c) Kobuke,
Y.; Satoh, Y. J . Am. Chem. Soc. 1992, 114, 789. (d) Kobuke, Y.; Kokubo,
K.; Munakata, M. J . Am. Chem. Soc. 1995, 117, 12751.
(4) (a) Dashkevich, L. B.; Boksiner, E. I. Zh. Obshch. Khim. 1958,
28, 2845. (b) Dashkevich, L. B.; Kuzmenkov, L. N. Zh. Obshch. Khim.
1959, 29, 2367. (c) Bryant, D. R.; Hauser, C. R. J . Org. Chem. 1961,
27, 694. (d) Poss, C. S.; Rychnovsky, S. D.; Schreiber, S. L. J . Am. Chem.
Soc. 1993, 115, 3360.
(9) (a) Curran, D. P. J . Am. Chem. Soc. 1982, 104, 4024. (b)
Kozikowski, A. P.; Adamczyk, M. Tetrahedron Lett. 1982, 23, 3123.
(10) Pulkkinen, J .; Vepsa¨la¨inen, J .; Laatikainen, R. Tetrahedron
Lett. 1994, 35, 9749.
(5) (a) Hauser, C. R.; Swamer, F. W.; Adams, J . T. Org. React. 1954,
8, 59. (b) Hause, H. O. Modern Synthetic Reactions; 2nd ed.; Ben-
jamin: Menlo Park, CA, 1972; pp 629-682.
(11) (a) Katayama, S.; Fukuda, K.; Watanabe, T.; Yamauchi, M.
Synthesis 1988, 178. (b) Katayama, S.; Watanabe, T.; Yamauchi, M.
Chem. Pharm. Bull. 1990, 38, 3314.
S0022-3263(96)00887-0 CCC: $12.00 © 1996 American Chemical Society

1,5-Diaryl-2,4-pentanediones and -4-methoxy-2-pentanones
J . Org. Chem., Vol. 61, No. 24, 1996 8605
Sch em e 1
respectively, the reaction led to unidentified mixtures.
According to our NMR studies of the reaction mixtures
of 4a , the first step of the reaction is an acid-catalyzed
dehydration of the alcohol 4 leading to R,â- and â,γ-
unsaturated ketones which are readily attacked by HCl
producing a 3-chloro ketone. If the reaction is quenched
too soon, this intermediate is found to be the main
product in the crude mixture which also includes small
amounts of the both unsaturated ketones. The last step
of the reaction is a nucleophilic substitution of chlorine
with methoxyl ion which leads to 5.
P r epar ation of Dim eth ylsu lfon iu m 1-(Ar ylacetyl)-
2-oxo-3-a r ylp r op ylid es 6. Using the procedure previ-
ously described by Katayama et al.,11 the hydroxy ketones
4 were converted to sulfur ylides 6 which were isolated
and characterized as stable intermediates before conver-
sion to the corresponding dicarbonyl compounds 7. The
reaction of 4 with a five-fold excess of the Corey-Kim
reagent (S,S-dimethylsuccinimidosulfonium chloride)12
under argon at -70 °C afforded 6, the yields being 43-
94%.
P r ep a r a tion of 1,5-Dia r yl-2,4-p en ta n ed ion es 7.
The diketones 7 were released with excellent yields from
S-ylides 6 by a reductive desulfurization with zinc in the
presence acetic acid at room temperature.11a The NMR
measurements established the tautomeric behavior of the
diketones 7, as both the diketone and the enol structures
were evident in the spectra. As expected, the energeti-
cally favorable enol tautomer was the dominating form
in all cases. The percentage of the diketone form was
only 12-20% in chloroform.
In summary we have presented the first general route
to produce 3-unsubstituted 1,5-diaryl-2,4-pentanediones
and -4-methoxy-2-pentanones having different aromatic
groups in the same structure. The method is based on a
[3 + 2] nitrile oxide-olefin cycloaddition which leads to
a 2-isoxazoline 3. This intermediate is converted to the
corresponding 3-hydroxy ketone 4 which may be used as
a precursor to both title compounds. All intermediates
and products are characterized by means of NMR and
mass spectrometry studies, and except for 7a ,4c they are
previously unreported.
Resu lts a n d Discu ssion
P r ep a r a tion of 3,5-Bis(a r ylm eth yl)-2-isoxa zolin es
3. 2-Isoxazolines are usually prepared by treating a
nitrile oxide, generated from an aldoxime or a primary
nitro compound, with an equimolar amount of olefin in
the presence of a catalytic amount of an organic base,
but in our case using equimolar quantities of the aryl
acetaldoxime 1 and the allylarene 2 gave only poor yields
and most of 2 remained unreacted. After optimizing the
amount of 1 as well as the reaction conditions by varying
the base, the solvent, and reaction temperature, we ended
up with a procedure where compounds 3a -h were
obtained by reacting a two-fold excess of 1 with 5%
sodium hypochlorite solution in a two-phase system in
the presence of 2 at 0 °C using a catalytic amount of
pyridine as the base in chloroform. Except for 3g and
3h , the yields were high.
Exp er im en ta l Section
P r epar ation of 1,5-Diar yl-4-h ydr oxy-2-pen tan on es
4. The isoxazolines 3 were smoothly converted to the
corresponding hydroxy ketones 4 by a catalytic reduction
with Raney nickel under hydrogen atmosphere in the
presence of water and acetic acid at room temperature
in high yields. In the case of the precursors 3a -e,
methanol was successfully used as a solvent. However,
the solubility of the isoxazolines 3f-h having bulky
nonpolar naphthyl groups in methanol was significantly
weaker and manifested itself in long reaction times and
poor yields. When methanol was replaced with tetrahy-
drofuran, which dissolved the isoxazolines easier and was
also miscible with the water needed for the hydrolysis of
the labile hydroxyimine intermediate resulting from the
N-O bond cleavage of the isoxazoline ring, the reaction
occurred easily giving high yields.
Gen er a l Meth od s. All moisture sensitive reactions were
performed under a positive pressure of argon in oven-dried
glassware equipped with rubber septa. Melting points were
measured with Stuart Scientific SMP2 apparatus and are
uncorrected. 1H and 13C NMR spectra (TMS/CDCl3) were
recorded on a Bruker AM 400 WB spectrometer operating at
400 and 101 MHz, respectively. All coupling constants are
given in Hz. Mass spectra were obtained on a Varian VG 70-
250SE spectrometer. Column chromatography was performed
with silica gel 60 (SiO2, 70-230 mesh).
Ma ter ia ls. In all the experiments involving the Corey-Kim
reagent, solvents and liquid reagents were dried, distilled,
stored under argon, and transferred using a syringe flushed
with argon. Aryl acetaldoximes 1 were synthesized from the
corresponding aldehydes and hydroxylamine hydrochloride.8b
Phenyl acetaldehyde was a commercial product and distilled
prior to use. 1- and 2-Naphthyl acetaldehydes were prepared
from the corresponding arylacetyl chlorides13 which were
obtained by reacting the corresponding carboxylic acids with
a slight excess of thionyl chloride. Allyl arenes 2 were either
commercial products or synthesized by allylating a phenol or
P r epar ation of 1,5-Diar yl-4-m eth oxy-2-pen tan on es
5. The methoxy ketones 5 were easily achieved with a
one flask synthesis by refluxing 4 in methanol overnight
in the presence of concentrated hydrochloric acid, usually
giving satisfactory yields. Only in the case of 4c and 4d ,
with 4-methoxyphenyl and 3,4-dimethoxyphenyl groups,
(12) Corey, E. J .; Kim, C. U. J . Am. Chem. Soc. 1972, 94, 7586.
(13) Brown, H. C.; Subba Rao, B. C. J . Am. Chem. Soc. 1958, 80,
5377.

8606 J . Org. Chem., Vol. 61, No. 24, 1996
Pulkkinen and Vepsa¨la¨inen
a naphthol via Claisen rearrangement to the corresponding
â-allyl product14 and then converting the hydroxyl group to
the methoxyl.15
126.1, 126.0, 125.6, 125.5, 125.4, 123.7, 123.4, 80.2 (15 d), 40.9,
37.7, 32.1 (3 t); MS m/ z (%) 351 (M+) (21), 210 (3), 141 (100),
115 (27); HRMS Calcd for C25H21NO: (M+) 351.16231.
Found: (M+) 351.16231.
Syn th esis of 3,5-Bis(a r ylm eth yl)-2-isoxa zolin es 3. To
a stirred solution of oxime 1 (20 mmol), alkene 2 (10 mmol),
and pyridine (4 mmol) in 100 mL of CHCl3 at 0 °C was added
5% NaOCl solution (40 mmol) during 1.5 h. The organic layer
was separated and washed with 2 M HCl, saturated NaHCO3,
and water and evaporated to give the product as an oil which
was purified by column chromatography using CH2Cl2 as an
eluent.
3-(2-Na p h t h ylm et h yl)-5-[(1-m et h oxy-2-n a p h t h yl)m e-
th yl]-2-isoxa zolin e (3g): yield 62%, a pale brown oil; 1H
NMR δ 7.96 (d, 1 H, J ) 8.4), 7.76-7.68 (m, 3 H), 7.62 (d, 1 H,
J ) 8.7), 7.57 (s, 1 H), 7.46 (d, 1 H, J ) 8.6), 7.44-7.39 (m, 4
H), 7.23 (d, 1 H, J ) 8.5), 7.18 (dd, 1 H, J ) 8.4, 1.9), 4.88 (m,
1 H), 3.75 (d, 1 H, J ) 14.8), 3.75 (s, 3 H), 3.70 (d, 1 H, J )
14.8), 3.13 (dd, 1 H, J ) 13.6, 5.8), 2.94 (dd, 1 H, J ) 13.6,
7.2), 2.72 (ddt, 1 H, J ) 17.1, 10.1, 0.8), 2.60 (ddt, 1 H, J )
17.1, 7.3, 0.7); 13C NMR δ 157.9, 154.1, 134.2, 133.5, 133.3,
132.4 (6 s), 128.6, 128.5, 128.0 (3 d), 127.9 (s), 127.6, 127.5,
127.4, 126.7, 126.2, 125.9, 125.7, 125.7 (8 d), 125.2 (s), 124.1,
122.0, 80.6 (3 d), 61.8 (q), 40.7, 34.7, 34.3 (3 t); MS m/ z (%)
381 (M+) (25), 210 (7), 171 (65), 141 (100); HRMS Calcd for
C26H23NO2: (M+) 381.17288. Found: (M+) 381.17288.
3-(2-Na p h t h ylm et h yl)-5-[(3-m et h oxy-2-n a p h t h yl)m e-
th yl]-2-isoxa zolin e (3h ): yield 36%, mp 144.5-145.0 °C; 1H
NMR δ 7.81-7.72 (m, 4 H), 7.68 (d, 1 H, J ) 8.0), 7.64 (d, 1 H,
J ) 9.0), 7.63 (s, 1 H), 7.44 (m, 2 H), 7.32 (dd, 1 H, J ) 8.4,
1.8), 7.22 (ddd, 1 H, J ) 8.0, 6.8, 1.3), 7.16 (ddd, 1 H, J ) 8.5,
6.8, 1.5), 7.09 (d, 1 H, J ) 9.0), 4.93 (m, 1 H), 3.86, 3.70 (2 d,
2 H, J ) 14.6), 3.61 (s, 3 H), 3.36 (dd, 1 H, J ) 13.4, 5.6), 3.31
(dd, 1 H, J ) 13.4, 8.8), 2.67 (ddt, 1 H, J ) 17.1, 6.0, 0.7), 2.60
(ddt, 1 H, J ) 17.1, 9.7, 0.7); 13C NMR δ 157.9, 154.9, 133.6,
133.5, 133.3, 132.5, 129.1 (7 s), 128.6, 128.5, 128.5, 127.6,
127.6, 127.4, 126.9, 126.6, 126.3, 125.8, 123.3, 123.0 (12 d),
117.7 (s), 112.8, 80.2 (2 d), 56.0 (q), 40.4, 34.4, 29.8 (3 t); MS
m/ z (%) 381 (M+) (25), 210 (2), 171 (100), 141 (81); HRMS
Calcd for C26H23NO2: (M+) 381.17288. Found: (M+) 381.17288.
Syn th esis of 1,5-Dia r yl-4-h yd r oxy-2-p en ta n on es 4. A
solution of isoxazoline 3 (10 mmol), AcOH (0.1 mol) and water
(1.0 mol), in 100 mL of MeOH (with 3e-h , 200 mL of THF
was used as the solvent) was stirred under H2 at rt overnight
in the presence of Raney Ni (1.5 g). The catalyst was removed
by filtering through Celite and the filtrate extracted by CH2-
Cl2. The extracts were washed with saturated NaHCO3 and
water and evaporated to give the pure product.
3,5-Diben zyl-2-isoxa zolin e (3a ): yield 82%, mp 57.0-57.5
1
°C; H NMR δ 7.29-7.09 (m, 10 H), 4.75 (m, 1 H), 3.62, 3.57
(2 d, 2 H, J ) 14.9), 2.95 (dd, 1 H, J ) 13.8, 5.9), 2.73 (dd, 1
H, J ) 17.1, 10.2), 2.72 (dd, 1 H, J ) 13.8, 7.1), 2.48 (dd, 1 H,
J ) 17.1, 7.5); 13C NMR δ 157.8, 136.9, 135.9 (3 s), 129.4, 128.8,
128.8, 128.5, 127.0, 126.6, 81.0 (7 d), 40.8, 40.6, 34.2 (3 t); MS
m/ z (%) 251 (M+) (3), 160 (13), 91 (100); HRMS Calcd for
C17H17NO: (M+) 251.13101. Found: (M+) 251.13101
3-Ben zyl-5-[(2-m et h oxyp h en yl)m et h yl]-2-isoxa zolin e
(3b): yield 78%, a pale brown oil; 1H NMR δ 7.36-7.16 (m, 6
H), 7.04 (d, 1 H, J ) 7.4), 6.85 (td, 1 H, J ) 7.4, 1.1), 6.79 (d,
1 H, J ) 8.2), 4.85 (m, 1 H), 3.72 (s, 3 H), 3.68, 3.61 (2 d, 2 H,
J ) 14.9), 3.03 (dd, 1 H, J ) 13.4, 5.7), 2.73 (dd, 1 H, J ) 13.4,
7.7), 2.72 (ddt, 1 H, J ) 17.1, 10.1, 0.9), 2.54 (ddt, 1 H, J )
17.1, 7.1, 0.8); 13C NMR δ 157.8, 157.4, 136.0 (3 s), 131.2, 128.8,
128.7, 127.9, 126.9 (5 d), 125.3 (s), 120.5, 110.3, 79.9 (3 d), 55.1
(q), 40.5, 35.3, 34.2 (3 t); MS m/ z (%) 281 (M+) (5), 160 (12),
121 (60), 91 (100); HRMS Calcd for C18H19NO2: (M+) 281.14158.
Found: (M+) 281.14158.
3-Ben zyl-5-[(4-m et h oxyp h en yl)m et h yl]-2-isoxa zolin e
(3c): yield 86%, a pale yellow oil; 1H NMR δ 7.31-7.23 (m, 3
H), 7.14-7.10 (m, 2 H), 7.03 (m, 2 H), 6.78 (m, 2 H), 4.72 (m,
1 H), 3.75 (s, 3 H), 3.63, 3.56 (2 d, 2 H, J ) 14.9), 2.88 (dd, 1
H, J ) 14.0, 5.8), 2.74 (ddt, 1 H, J ) 17.0, 10.2, 0.9), 2.69 (dd,
1 H, J ) 14.0, 6.8), 2.48 (ddt, 1 H, J ) 17.0, 7.6, 0.8 Hz); 13C
NMR δ 158.4, 157.7, 135.9 (3 s), 130.4 (d), 128.9 (s), 128.8,
128.7, 127.0, 113.9, 81.2 (5 d), 55.2 (q), 40.4, 39.8, 34.2 (3 t);
MS m/ z (%) 281 (M+) (5), 160 (5), 121 (100), 91 (42); HRMS
Calcd for C18H19NO2: (M+) 281.14158. Found: (M+) 281.14158.
3-Ben zyl-5-[(3,4-d im eth oxyp h en yl)m eth yl]-2-isoxa zo-
1,5-Dip h en yl-4-h yd r oxy-2-p en ta n on e (4a ): yield 89%, a
pale yellow oil; 1H NMR δ 7.35-7.15 (m, 10 H), 4.26 (m, 1 H),
3.68 (s, 2 H), 3.29 (s, 1 H), 2.79 (dd, 1 H, J ) 13.6, 7.3) 2.69
(dd, 1 H, J ) 13.6, 6.0), 2.58 (d, 1 H, J ) 4.8), 2.57 (d, 1 H, J
) 7.2); 13C NMR δ 208.9, 137.9, 133.6 (3 s), 129.5, 129.4, 128.8,
128.5, 127.2, 126.6, 68.8 (7 d), 50.8, 47.6, 42.9 (3 t); MS m/ z
(%) 254 (M+) (1), 236 (M+ - H2O) (15), 121 (64), 119 (35), 91
(100); HRMS Calcd for C17H16O: (M+ - H2O) 236.12011.
Found: (M+ - H2O) 236.12012.
1
lin e (3d ): yield 81%, a pale yellow oil; H NMR δ 7.29-7.18
(m, 3 H), 7.15-7.08 (m, 2 H), 6.72 (d, 1 H, J ) 8.1), 6.66 (d, 1
H, J ) 2.0), 6.64 (dd, 1 H, J ) 8.1, 2.0), 4.74 (m, 1 H), 3.79 (s,
3 H), 3.77 (s, 3 H), 3.63, 3.53 (2 d, 2 H, J ) 14.9), 2.85 (dd, 1
H, J ) 14.0, 5.9), 2.75 (ddt, 1 H, J ) 17.0, 10.3, 0.8), 2.69 (dd,
1 H, J ) 14.0, 6.4), 2.48 (ddt, 1 H, J ) 17.0, 7.4, 0.7); 13C NMR
δ 157.7, 148.9, 147.8, 135.9, 129.4 (5 s), 128.7, 128.7, 126.9,
121.4, 112.8, 111.3, 81.0 (7 d), 55.8, 55.8 (2 q), 40.3, 40.2, 34.0
(3 t); MS m/ z (%) 311 (M+) (28), 160 (16), 151 (100), 91 (52);
HRMS Calcd for C19H21NO3: (M+) 311.15214. Found: (M+)
311.15214.
1-P h en yl-5-(2-m et h oxyp h en yl)-4-h yd r oxy-2-p en t a n -
on e (4b): yield 75%, a greenish brown viscous oil; 1H NMR δ
7.32-7.13 (m, 6 H), 7.08 (dd, 1 H, J ) 7.4, 1.8), 6.87 (td, 1 H,
J ) 7.4, 1.1), 6.83 (dd, 1 H, J ) 8.2, 1.1), 4.30 (m, 1 H), 3.77 (s,
3 H), 3.66 (s, 2 H), 2.82 (dd, 1 H, J ) 13.4, 6.8), 2.77 (dd, 1 H,
3-Be n zyl-5-[(p e n t a flu or op h e n yl)m e t h yl]-2-isoxa zo-
lin e (3e): yield 92%, mp 77-79 °C; 1H NMR δ 7.34-7.19 (m,
5 H), 4.77 (m, 1 H), 3.70, 3.63 (2 d, 2 H, J ) 14.9), 2.97 (ddt,
J ) 13.4, 6.0), 2.59 (d, 1 H, J ) 6.1), 2.59 (d, 1 H, J ) 5.8); 13
C
4
NMR δ 208.9, 157.6, 133.9 (3 s), 131.4, 129.5, 128.7, 128.0,
127.1 (5 d), 126.2 (s), 120.6, 110.5, 67.9 (3 d), 55.3 (q), 50.7,
48.0, 37.5 (3 t); MS m/ z (%) 266 (M+ - H2O) (100), 193 (8),
175 (24), 163 (13), 121 (11), 91 (9); HRMS Calcd for C18H20O3:
(M+) 284.14124. Found: (M+) 284.14124.
1 H, J ) 13.9, 7.1, J HF ) 1.3), 2.93 (dd, 1 H, J ) 17.4, 10.2),
4
2.84 (ddt, 1 H, J ) 13.9, 6.0, J HF )1.4), 2.52 (dd, 1 H, J )
17.4, 7.5); 13C NMR δ 157.6 (s), 145.4, 140.2 (2 d), 137.5 (d),
135.5 (s), 128.9, 128.7 (2 d), 127.3 (d), 110.4 (s), 78.2 (d), 41.1,
34.1, 27.9 (3 t); MS m/ z (%) 341 (M+) (1), 181 (13), 160 (15),
91 (100); HRMS Calcd for C17H12F5NO: (M+) 341.08389.
Found: (M+) 341.08391.
1-P h en yl-5-(4-m et h oxyp h en yl)-4-h yd r oxy-2-p en t a n -
1
on e (4c): yield 76%, a pale yellow oil; H NMR δ 7.32-7.23
(m, 3 H), 7.16-7.12 (m, 2 H), 7.05 (m, 2 H), 6.80 (m, 2 H),
4.19 (m, 1 H), 3.74 (s, 3 H), 3.65 (s, 2 H), 2.69 (dd, 1 H, J )
13.7, 7.2), 2.61 (dd, 1 H, J ) 13.7, 6.0), 2.59 (dd, 1 H, J ) 17.4,
4.5), 2.55 (dd, 1 H, J ) 17.4, 7.5); 13C NMR δ 208.8, 158.3,
133.7 (3 s), 130.3 (d), 129.9 (s), 129.5, 128.7, 127.1, 114.0, 68.9
(5 d), 55.2 (q), 50.7, 47.6, 42.0 (3 t); MS m/ z (%) 284 (M+) (8),
266 (M+ - H2O) (100), 175 (11), 147 (37), 134 (27), 121 (13),
91 (5); HRMS Calcd for C18H20O3: (M+) 284.14124. Found:
(M+) 284.14124.
3,5-Bis-(1-n aph th ylm eth yl)-2-isoxazolin e (3f): yield 84%,
a pale yellow oil; H NMR δ 8.16 (d, 1 H, J ) 8.3), 7.90-7.78
1
(m, 4 H), 7.66 (d, 1 H, J ) 8.3), 7.58-7.49 (m, 2 H), 7.45-7.38
(m, 3 H), 7.31 (d, 1 H, J ) 7.0), 7.23 (dd, 1 H, J ) 8.3, 7.0),
6.91 (dd, 1 H, J ) 7.0, 1.2), 4.91 (m, 1 H), 4.18, 4.06 (2 d, 2 H,
J ) 15.2), 3.46 (dd, 1 H, J ) 14.0, 5.7), 2.93 (dd, 1 H, J ) 14.0,
8.3), 2.63 (ddt, 1 H, J ) 17.1, 10.0, 1.0), 2.44 (ddt, J ) 14.0,
6.8, 0.8); 13C NMR δ 158.1, 134.0, 133.8, 132.8, 132.0, 131.9,
131.8 (7 s,) 128.8, 128.8, 128.1, 127.4, 127.3, 127.3, 126.6,
1-P h en yl-5-(3,4-d im et h oxyp h en yl)-4-h yd r oxy-2-p en -
1
ta n on e (4d ): yield 90%, a yellow oil; H NMR δ 7.34-7.23
(14) White, W. N.; Gwynn, D.; Schlitt, R.; Girard, C.; Fife, W J . Am.
Chem. Soc. 1958, 80, 3271.
(15) Vyas, G. N.; Shah, N. M. Organic Syntheses; Wiley: New York,
Coll. Vol. 4, 1963; p 836.
(m, 3 H), 7.17-7.14 (m, 2 H), 6.80-6.66 (m, 3 H), 4.22 (m. 1
H), 3.84 (s, 3 H), 3.83 (s, 3 H), 3.68 (s, 2 H), 2.70 (dd, 1 H, J )
13.7, 7.3), 2.63 (dd, 1 H, J ) 13.7, 5.9), 2.61 (d, 1 H, J ) 4.2),

1,5-Diaryl-2,4-pentanediones and -4-methoxy-2-pentanones
J . Org. Chem., Vol. 61, No. 24, 1996 8607
2.60 (d, 1 H, J ) 7.7); 13C NMR δ 208.9, 149.0, 147.8, 133.6,
130.4 (5 s), 129.5, 128.8, 127.2, 121.4, 112.6, 111.4, 68.8 (7 d),
55.9, 55.9 (2 q), 50.8, 47.7, 42.5 (3 t); MS m/ z (%) 314 (M+)
(10), 298 (M+ - H2O) (1), 205 (7), 181 (7), 151 (42), 91 (100);
HRMS Calcd for C19H22O4: (M+) 314.15181. Found: (M+)
314.15181.
1-P h en yl-5-(p en ta flu or op h en yl)-4-h yd r oxy-2-p en ta n -
on e (4e): yield 88%, mp 68.5-69.0 °C; 1H NMR δ 7.35-7.16
(m, 5 H), 4.24 (m, 1 H), 3.72, (s, 2 H), 2.99 (d, OH, J ) 4.2,
coupled due to strong hydrogen bonding), 2.88 (ddt, 1 H, J )
13.8, 7.9, 4J HF ) 1.6), 2.76 (ddt, 1 H, J ) 13.8, 5.3, 4J HF ) 1.6),
2.70 (dd, 1 H, J ) 17.9, 3.4), 2.63 (dd, 1 H, J ) 17.9, 8.2); 13C
NMR δ 208.68 (s), 145.5, 140.0, 137.5 (3 d), 133.3 (s), 129.5,
128.9, 127.4 (3 d), 111.5 (s), 66.7 (d), 50.8, 47.3, 29.1 (3 t); MS
m/ z (%) 344 (M+) (3), 326 (M+ - H2O) (5), 253 (29), 235 (58),
211 (63), 181 (43), 91 (100); HRMS Calcd for C17H13F5O2: (M+)
344.08356. Found: (M+) 344.08357.
7.4, 1.1), 6.81 (dd, 1 H, J ) 8.2, 1.1), 3.97 (m, 1 H), 3.77 (s, 3
H), 3.67, 3.62 (2 d, 2 H, J ) 15.9), 3.31 (s, 3 H), 3.01 (dd, 1 H,
J ) 13.3, 5.4), 2.63 (dd, 1 H, J ) 16.0, 8.4), 2.62 (dd, 1 H, J )
13.3, 7.4), 2.43 (dd, 1 H, J ) 16.0, 4.0); 13C NMR δ 206.9, 157.6,
134.2 (3 s), 131.3, 129.6, 128.6, 127.8, 126.9 (5 d), 126.3 (s),
120.5, 110.4, 77.3 (3 d), 57.3, 55.2 (2 q), 50.8, 46.7, 34.5 (3 t);
MS m/ z (%) 266 (M+ - MeOH) (40), 175 (16), 147 (36), 121
(38), 119 (26), 91 (100); HRMS Calcd for C19H22O3: (M+)
298.15689. Found: (M+) 298.15693.
1-P h e n yl-5-(p e n t a flu or op h e n yl)-4-m e t h oxy-2-p e n -
1
ta n on e (5e): yield 75%, a pale yellow oil; H NMR δ 7.34-
7.12 (m, 5 H), 3.92 (m, 1 H), 3.70 (s, 2 H), 3.30 (s, 3 H), 2.88
(m, 2 H), 2.73 (dd, 1 H, J ) 16.8, 7.5), 2.44 (dd, 1 H, J ) 16.8,
5.1); 13C NMR δ 205.9 (s), 145.5, 140.0, 137.4 (3 d), 133.7 (s),
129.5, 128.8, 127.2 (3 d), 111.2 (s), 75.9 (d), 57.7 (q), 50.9, 46.0,
26.5 (3 t); MS m/ z (%) 358 (M+) (9), 267 (16), 225 (100), 181
(14), 177 (23); HRMS Calcd for C18H15F5O2: (M+) 358.09921.
Found: (M+) 358.09920.
1,5-Di(1-n a p h th yl)-4-h yd r oxy-2-p en ta n on e (4f): yield
93%, a pale brown viscous oil; 1H NMR δ 8.00-7.96 (m, 1 H),
7.84-7.77 (m, 3 H), 7.75, 7.69 (2 d, 2 H, J ) 8.2), 7.48-7.41
(m, 4 H), 7.36, 7.30 (2 dd, 2 H, J ) 8.2, 7.0), 7.24, 7.18 (2 dd,
2 H, J ) 7.0, 1.2), 4.36 (m, 1 H), 4.05, 4.02 (2 d, 2 H, J ) 16.1),
3.11 (d, 2 H, J ) 6.7), 2.63 (dd, 1 H, J ) 17.5, 8.1), 2.61 (dd, 1
H, J ) 17.5, 3.8); 13C NMR δ 209.2, 134.0, 134.0, 133.9, 132.2,
132.1, 130.4 (7 s), 128.9, 128.8, 128.3, 128.2, 127.6, 127.5,
126.6, 126.1, 126.0, 125.7, 125.5, 125.4, 123.9, 123.7, 68.2 (15
1,5-Di(1-n a p h th yl)-4-m eth oxy-2-p en ta n on e (5f): yield
40%, a pale brown oil; 1H NMR δ 8.04 (d, 1 H, J ) 8.1), 7.86-
7.78 (m, 3 H), 7.75 (d, 1 H, J ) 8.3), 7.71 (d, 1 H, J ) 8.2),
7.52-7.42 (m, 4 H), 7.37 (dd, 1 H, J ) 8.3, 7.0), 7.33 (dd, 1 H,
J ) 8.2, 7.0), 7.26 (d, 2 H, J ) 7.0), 4.09 (d, 1 H, J ) 16.2),
4.06 (m, 1 H), 4.04 (d, 1 H, J ) 16.2), 3.29 (dd, 1 H, J ) 13.9,
6.6), 3.21 (s, 3 H), 3.08 (dd, 1 H, J ) 13.9, 6.4), 2.75 (dd, 1 H,
J ) 16.3, 7.3), 2.49 (dd, 1 H, J ) 16.3, 5.0); 13C NMR δ 207.1,
134.2, 133.9, 133.9, 132.3, 132.2, 130.7 (7 s), 128.8, 128.7,
128.3, 128.0, 127.9, 127.2, 126.4, 126.0, 125.8, 125.5, 125.5,
125.4, 123.9, 123.8, 78.0 (15 d), 57.7 (q), 49.3, 46.4, 37.5 (3 t);
MS m/ z (%) 368 (M+) (2), 336 (M+ - MeOH) (14), 200 (27),
184 (16), 167 (26), 153 (53), 141 (100); HRMS Calcd for
C26H24O2: (M+) 368.17763. Found: (M+) 368.17763.
1-(2-Na p h th yl)-5-(1-m eth oxy-2-n a p h th yl)-4-m eth oxy-2-
p en ta n on e (5g): yield 32%, a pale brown oil; 1H NMR δ 8.06
(d, 1 H, J ) 8.2), 7.82-7.70 (m, 4 H), 7.56 (s, 1H), 7.52 (d, 1 H,
J ) 8.3), 7.52-7.40 (m, 4 H), 7.29 (d, 1 H, J ) 8.4), 7.22 (dd,
1 H, J ) 8.8, 1.7), 4.07 (m, 1 H), 3.88 (s, 3 H), 3.81 (s, 2 H),
3.32 (s, 3 H), 3.11 (dd, 1 H, J ) 13.5, 5.8), 2.88 (dd, 1 H, J )
13.5, 6.6), 2.72 (dd, 1 H, J ) 16.4, 7.3), 2.57 (dd, 1 H, J ) 16.4,
5.1); 13C NMR δ 206.8, 154.1, 134.1, 133.5, 132.4, 131.6 (6 s),
129.0, 128.3, 128.2, 128.0 (4 d), 128.0 (s), 127.6, 127.6, 127.6
(3 d), 126.4 (s), 126.1, 125.9, 125.7, 125.7, 124.0, 122.1, 78.0
(7 d), 61.9, 57.4 (2 q), 51.0, 46.4, 33.9 (3 t); MS m/ z (%) 398
(M+), (22), 366 (M+ - MeOH) (31), 257 (5), 225 (29), 197 (40),
171 (66), 141 (100); HRMS Calcd for C27H26O3: (M+) 398.18819.
Found: (M+) 398.18819.
d), 48.9, 47.5, 40.0 (3 t); MS m/ z (%) 354 (M+) (5), 336 (M+
-
H2O), 213 (5), 183 (5), 153 (21), 141 (100); HRMS Calcd for
C25H22O2: (M+) 354.16198. Found: (M+) 354.16198.
1-(2-Na p h th yl)-5-(1-m eth oxy-2-n a p h th yl)-4-h yd r oxy-2-
p en ta n on e (4g): yield 71%, a pale brown oil; 1H NMR δ 8.04
(d, 1 H, J ) 8.3), 7.79-7.69 (m, 4 H), 7.56 (s, 1 H), 7.51-7.40
(m, 5 H), 7.22 (dd, 1 H, J ) 8.3, 2.1), 7.22 (d, 1 H, J ) 8.5),
4.36 (m, 1 H), 3.85 (s, 3 H), 3.81, 3.76 (2 d, 2 H, J ) 15.4), 2.99
(dd, 1 H, J ) 13.5, 6.8), 2.94 (dd, 1 H, J ) 13.5, 6.3), 2.65 (d,
1 H, J ) 6.6), 2.65 (d, 1 H, J ) 5.2); 13C NMR δ 209.1, 154.0,
134.2, 133.5, 132.4, 131.2 (6 s), 128.8, 128.3, 128.3, 128.1 (4
d), 127.9 (s), 127.7, 127.6, 127.5 (3 d), 126.2 (s), 126.2, 126.0,
125.8, 125.8, 124.2, 122.0, 68.6 (7 d), 61.8 (q), 50.7, 47.6, 36.9
(3 t); MS m/ z (%) 384 (M+) (10), 366 (M+ - H2O) (13), 225
(11), 183 (10), 171 (25), 141 (100); HRMS Calcd for C26H24O3:
(M+) 384.17254. Found: (M+) 384.17254.
1-(2-Na p h th yl)-5-(3-m eth oxy-2-n a p h th yl)-4-h yd r oxy-2-
1
p en ta n on e (4h ): yield 95%, a brown oil; H NMR δ 7.96 (d,
1 H, J ) 8.7), 7.73-7.63 (m, 5 H), 7.47 (s, 1 H), 7.42-7.34 (m,
3 H), 7.28 (ddd, 1 H, J ) 8.1, 6.8, 1.1), 7.14 (dd, 1 H, J ) 8.5,
1.7), 7.10 (d, 1 H, J ) 9.1), 4.39 (m, 1 H), 3.71 (s, 3 H), 3.68,
3.64 (2 d, 2 H, J ) 15.7), 3.26 (d, 1 H, J ) 7.0), 3.26 (d, 1 H,
J ) 6.6), 2.68 (dd, 1 H, J ) 17.5, 8.0), 2.56 (dd, 1 H, J ) 17.5,
3.9); 13C NMR δ 209.2, 154.8, 133.4, 133.4, 132.3, 131.3, 129.2
(7 s), 128.5, 128.5, 128.2, 128.2, 127.6, 127.5, 127.5, 126.6,
126.1, 125.7, 123.3, 123.3 (12 d), 119.0 (s), 112.9, 68.3 (2 d),
56.1 (q), 50.6, 48.1, 31.9 (3 t); MS m/ z (%) 384 (M+) (10), 366
(M+ - H2O) (9), 197 (14), 171 (34), 165 (22), 141 (100); HRMS
Calcd for C26H24O3: (M+) 384.17254. Found: (M+) 384.17254.
Syn th esis of 1,5-Dia r yl-4-m eth oxy-2-p en ta n on es 5. To
a stirred solution of hydroxy ketone 4 (1 mmol) in 25 mL of
MeOH was added dropwise concd HCl (0.2 mL) at 0 °C, and
the mixture was refluxed overnight. Then the solution was
taken up with CH2Cl2, washed with saturated NaHCO3 and
water, and evaporated. The residue was purified by column
chromatography using chloroform as an eluent to afford the
pure product.
1-(2-Na p h th yl)-5-(3-m eth oxy-2-n a p h th yl)-4-m eth oxy-2-
1
p en ta n on e (5h ): yield 83%, a brown viscous oil; H NMR δ
7.98 (d, 1 H, J ) 8.7), 7.78-7.68 (m, 5 H), 7.50 (s, 1 H), 7.46-
7.40 (m, 3 H), 7.30 (ddd, 1 H, J ) 8.0, 6.8, 1.1), 7.17 (d, 1 H,
J ) 9.0), 7.16 (dd, 1 H, J ) 8.4, 1.8), 4.10 (m, 1 H), 3.82 (s, 3
H), 3.72 (s, 2 H), 3.43 (dd, 1 H, J ) 13.4, 5.6), 3.36 (s, 3 H),
3.16 (dd, 1 H, J ) 13.4, 8.2), 2.79 (dd, 1 H, J ) 16.3, 8.6), 2.43
(dd, 1 H, J ) 16.3, 3.8); 13C NMR δ 207.1, 155.0, 133.5, 133.4,
132.4, 131.7, 129.2 (7 s), 128.5, 128.4, 128.2, 128.1, 127.6,
127.6, 127.6, 126.5, 126.0, 125.7, 123.3, 123.3 (12 d), 119.1 (s),
113.0, 77.7 (2 d), 57.5, 56.2 (2 q), 50.9, 47.1, 29.3 (3 t); MS
m/ z (%) 398 (M+) (43), 366 (M+ - MeOH) (38), 257 (12), 215
(12), 201 (16), 197 (38), 183 (19), 171 (90), 141 (100); HRMS
Calcd for C27H26O3: (M+) 398.18819. Found: (M+) 398.18819.
Syn th esis of Dim eth ylsu lfon iu m 1-(Ar yla cetyl)-2-oxo-
3-a r ylp r op ylid es 6. To a stirred suspension of NCS (20
mmol) in 60 mL of anhydrous CH2Cl2 was added dropwise
dimethyl sulfide (40 mmol) at -70 °C under argon and stirring
was continued for 1 h. Then a solution of hydroxy ketone 4
(4.0 mmol) in 6 mL of CH2Cl2 was added, maintaining the same
temperature, and the solution was stirred for 1 h. Triethyl-
amine (60 mmol) was then added and after 1 h the reaction
mixture was treated with saturated brine (20 mL). This
mixture was extracted with ether and the organic layer washed
with saturated brine and evaporated. The residue was puri-
fied by column chromatography using 95:5 chloroform-acetone
as an eluent to give 6.
1,5-Dip h en yl-4-m eth oxy-2-p en ta n on e (5a ): yield 78%,
1
a pale yellow oil; H NMR δ 7.34-7.14 (m, 10 H), 3.90 (m, 1
H), 3.65 (s, 2 H), 3.28 (s, 3 H), 2.84 (dd, 1 H, J ) 13.7, 6.0),
2.70 (dd, 1 H, J ) 13.7, 6.4), 2.64 (dd, 1 H, J ) 16.3, 7.5), 2.44
(dd, 1 H, J ) 16.3, 4.9); 13C NMR δ 207.0, 138.2, 134.2 (3 s),
129.8, 129.8, 128.9, 128.6, 127.3, 126.6, 78.6 (7 d), 57.7 (q),
51.3, 46.5, 40.2 (3 t); MS m/ z (%) 268 (M+) (1), 236 (M+
-
MeOH) (54), 177 (49), 135 (82), 119 (66), 117 (48), 91 (100);
HRMS Calcd for C18H20O2: (M+) 268.14632. Found: (M+)
268.14633.
1-P h en yl-5-(2-m et h oxyp h en yl)-4-m et h oxy-2-p en t a n -
on e (5b): yield 52%, a pale yellow oil; H NMR δ 7.30-7.10
(m, 6 H), 7.08 (ddd, 1 H, J ) 7.4, 1.8, 0.4), 6.85 (td, 1 H, J )
Dim eth ylsu lfon iu m 1-(p h en yla cetyl)-2-oxo-3-p h en yl-
p r op ylid e (6a ): yield 80%, a pale yellow viscous oil; 1H NMR
δ 7.30-7.18 (m, 10 H), 4.07 (br s, 4 H), 2.63 (s, 6 H); 13C NMR
1

8608 J . Org. Chem., Vol. 61, No. 24, 1996
Pulkkinen and Vepsa¨la¨inen
δ 191.4, 137.1 (2 s), 129.5, 128.4, 126.3 (3 d), 85.4 (s), 48.7 (t),
26.5 (q); MS m/ z (%) 312 (M+) (17), 250 (21), 221 (86), 206
(18), 91 (100); HRMS Calcd for C19H20O2S: (M+) 312.11839.
Found: (M+) 312.11840.
1,5-Dip h en yl-2,4-p en ta n ed ion e (7a ): yield 88%, mp 64-
65 °C (lit. mp 65.2-66.5 °C);4c enol form (85%): 1H NMR δ
15.27 (br, OH), 7.32-7.19 (m, 10 H), 5.42 (s, 1 H), 3.55 (s, 4
H); 13C NMR δC 192.3, 135.1 (2 s), 129.4, 128.7, 127.1, 99.6 (4
d), 45.1 (t); diketone form (15%): 1H NMR δH 7.27-7.11 (m,
10 H), 3.68 (s, 4 H), 3.55 (s, 2 H); 13C NMR δ 201.8, 133.3 (2
s), 129.7, 129.0, 127.4 (3 d), 54.8, 50.7 (2 t); MS m/ z (%) 252
(M+) (5), 161 (99), 133 (6), 119 (8), 91 (100); HRMS: Calcd for
Dim eth ylsu lfon iu m 1-(p h en yla cetyl)-2-oxo-3-(2-m eth -
oxyp h en yl)p r op ylid e (6b): yield 75%, a pale yellow viscous
1
oil; H NMR δ 7.30-7.24 (m, 4 H), 7.21-7.16 (m, 2 H), 7.08
(dd, 1 H, J ) 7.4, 1.5), 6.86 (td, 1 H, J ) 7.4, 1.1), 6.83 (dd, 1
H, J ) 7.9, 1.1), 4.10, 4.00 (2 br s, 4 H), 3.74 (s, 3 H) 2.63 (s,
6 H); 13C NMR δ 191.5, 157.3, 137.4 (3 s), 130.8, 129.5, 128.2,
127.7, 126.1 (5 d), 126.0 (s), 120.5, 110.5 (2 d), 85.7 (s), 55.4
(q), 48.4, 42.8 (2 t), 26.5, 26.5 (2 q); MS m/ z (%) 342 (M+) (17),
251 (18), 221 (65), 121 (79), 91 (100); HRMS Calcd for
C20H22O3S: (M+) 342.12897. Found: (M+) 342.12897.
C
17H16O2: (M+) 252.11502. Found: (M+) 252.11503.
1-P h en yl-5-(2-m eth oxyp h en yl)-2,4-p en ta n ed ion e (7b):
yield 82%, a pale yellow oil; enol form (80%): 1H NMR δ 15.29
(br, OH), 7.30-7.10 (m, 7 H), 6.89 (td, 1 H, J ) 7.4, 1.1), 6.83
(dd, 1 H, J ) 8.2, 0.9), 5.39 (s, 1 H), 3.71 (s, 3 H), 3.55, 3.50 (2
s, 4 H); 13C NMR δ 194.3, 190.2, 157.4, 135.3 (4 s), 131.0, 129.3,
128.8, 128.6, 126.9 (5 d), 123.6 (s), 120.6, 110.6, 99.3 (3 d), 55.3
(q), 44.5, 39.8 (2 t); diketone form (20%): 1H NMR δ 7.31-
7.10 (m, 6 H), 7.06 (dd, 1 H, J ) 7.7, 1.4 Hz), 6.90 (td, 1 H, J
) 7.4, 1.1 Hz), 6.84 (dd, 1 H, J ) 8.2, 0.9 Hz), 3.73 (s, 3 H),
3.67, 3.61, 3.52 (3 s, 6 H); 13C NMR δ 202.4, 202.0, 157.3, 133.5
(4 s), 131.4, 129.6, 128.9, 128.6, 127.2 (5 d), 122.6 (s), 120.8,
110.5 (2 d), 55.3 (q), 54.7, 50.3, 45.5 (3 t); MS m/ z (%) 282
(M+) (3), 191 (10), 161 (24), 148 (10), 121 (38), 91 (100); HRMS
Calcd for C18H18O3: (M+) 282.12559. Found: (M+) 282.12559.
Dim eth ylsu lfon iu m 1-(p h en yla cetyl)-2-oxo-3-(4-m eth -
oxyp h en yl)p r op ylid e (6c): yield 56%, a pale yellow viscous
oil; 1H NMR: δ 7.30-7.16 (m, 5 H), 7.13, 6.81 (2 m, 4 H), 4.06,
3.99 (2 br s, 4 H), 3.76 (s, 3 H) 2.62 (s, 6 H); 13C NMR δ 191.7,
158.4, 137.4 (3 s), 130.6, 129.7 (2 d), 129.4 (s), 128.6, 126.5,
114.1 (3 d), 85.7 (s), 55.5 (q), 48.8, 47.9 (2 t), 26.7 (q); MS m/ z
(%) 342 (M+) (3), 280 (10), 251 (3), 221 (12), 121 (100); HRMS
Calcd for C20H22O3S: (M+) 342.12897. Found: (M+) 342.12897.
Dim eth ylsu lfon iu m 1-(ph en ylacetyl)-2-oxo-3-(3,4-dim e-
th oxyp h en yl)p r op ylid e (6d ): yield 94%, a pale brown
viscous oil; 1H NMR δ 7.30-7.16 (m, 5 H), 6.81-6.78 (m, 3
H), 4.06, 4.02 (2 br s, 4 H), 3.85, 3.82 (2 s, 6 H), 2.66 (s, 6 H);
13C NMR δ 192.2, 191.1, 148.9, 147.6, 137.1, 129.6 (6 s), 129.4,
128.4, 126.3, 121.6, 112.6, 111.2 (6 d), 85.4 (s), 55.9, 55.9 (2
q), 48.6, 48.1 (2 t), 26.5, 26.5 (2 q); MS m/ z (%) 372 (M+) (10),
310 (59), 221 (37), 191 (56), 151 (100); HRMS Calcd for
C21H24O4S: (M+) 372.13953. Found: (M+) 372.13953.
1-P h en yl-5-(4-m eth oxyp h en yl)-2,4-p en ta n ed ion e (7c):
yield 77%, mp 66-67 °C; enol form (88%): 1H NMR δ 15.29
(br, OH), 7.32-7.17 (m, 5 H), 7.10 (m, 2 H), 6.83 (m, 2 H),
5.41 (s, 1 H), 3.76 (s, 3 H), 3.53, 3.47 (2 s, 4 H); 13C NMR δ
192.7, 192.2, 158.7, 135.0 (4 s), 130.3, 129.3, 128.6, 127.0 (4
d), 127.0 (s), 114.1, 99.4 (2 d), 55.2 (q), 45.0, 44.1 (2 t); diketone
form (12%): 1H NMR δ 7.32-7.17 (m, 7 H), 7.01 (m, 2 H), 3.75
(s, 3 H), 3.67, 3.60, 3.52 (3 s, 6 H); 13C NMR δ 202.2, 201.9,
158.7, 133.3 (4 s), 130.6, 129.6, 128.6, 127.3 (4 d), 125.2 (s),
114.3 (d), 55.2 (q), 54.5, 50.6, 49.7 (3 t); MS m/ z (%) 282 (M+)
(5), 191 (14), 161 (48), 148 (21), 121 (100); HRMS Calcd for
Dim eth ylsu lfon iu m 1-(ph en ylacetyl)-2-oxo-3-(pen taflu -
1
or op h en yl)p r op ylid e (6e): yield 92%, mp 127-129 °C; H
NMR δ 7.34-7.21 (m, 5 H), 4.33, 3.92 (2 br s, 4 H), 2.71 (s, 6
H); 13C NMR δ 190.0, 188.6 (2 s), 145.5, 139.9, 137.3 (3 d),
136.6 (s), 129.2, 128.8, 126.7 (3 d), 111.3, 85.2 (2s), 48.4, 36.2
(2 t), 26.7 (q); MS m/ z (%) 402 (M+) (3), 311 (22), 181 (36),
118 (17), 91 (100); HRMS Calcd for C19H15F5O2S: (M+)
402.07128. Found: (M+) 402.07129.
C
18H18O3: (M+) 282.12559. Found: (M+) 282.12559.
1-P h en yl-5-(3,4-d im et h oxyp h en yl)-2,4-p en t a n ed ion e
(7d ): yield 68%, a pale yellow oil; enol form (85%): 1H NMR
δ 15.29 (br, OH), 7.32-7.20 (m, 3 H), 7.20-7.14 (m, 2 H), 6.79
(d, 1 H, J ) 8.1), 6.72 (ddt, 1 H, J ) 8.1, 2.0, 0.5), 6.69 (d, 1 H,
J ) 2.0), 5.42 (s, 1 H), 3.83, 3.81 (2 s, 6 H), 3.53, 3.47 (2 s, 4
H); 13C NMR δ 192.7, 192.1, 149.0, 148.1, 135.0 (5 s), 129.3,
128.6 (2 d), 127.4 (s), 127.0, 121.5, 112.4, 111.3, 99.3 (5 d), 55.8,
55.8 (2 q), 45.0, 44.6 (2 t); diketone form (15%): 1H NMR δ
7.24-7.17 (m, 3 H), 7.12-7.08 (m, 2 H), 6.78 (d, 1 H, J ) 8.1),
6.65 (ddt, 1 H, J ) 8.1, 2.0, 0.5), 6.62 (d, 1 H, J ) 2.0), 3.83,
3.80 (2 s, 6 H), 3.66, 3.61, 3.54 (3 s, 6 H); 13C NMR δ 202.2,
201.9, 149.2, 148.4, 133.2 (5 s), 129.6, 128.8 (2 d), 127.3 (s),
125.7, 121.8, 112.6, 111.5 (4 d), 55.8, 55.8 (2 q), 54.5, 50.5, 50.1
(3 t); MS m/ z (%) 312 (13), 221 (6), 178 (30), 161 (68), 151
(100); HRMS Calcd for C19H20O4: (M+) 312.13616. Found:
(M+) 312.13616.
Dim et h ylsu lfon iu m 1-(1-n a p h t h yla cet yl)-2-oxo-3-(1-
n a p h th yl)p r op ylid e (6f): yield 72%, mp 69-70 °C, 1H NMR
δ 7.94, 7.82, 7.72 (3 m, 6 H), 7.47-7.35 (m, 8 H), 4.53 (br s, 4
H), 2.42 (s, 6 H); 13C NMR δ 191.7, 133.8, 133.8, 132.4 (4 s),
128.6, 127.7, 127.2, 126.0, 125.6, 125.4, 124.3 (7 d), 86.3 (s),
46.3 (t), 26.4 (q); MS m/ z (%) 412 (M+) (1), 350 (11), 271 (9),
141 (100), 115 (30); HRMS Calcd for C27H24O2S: (M+) 412.14970.
Found: (M+) 412.14970.
Dim et h ylsu lfon iu m 1-(2-n a p h t h yla cet yl)-2-oxo-3-(1-
m eth oxy-2-n a p h th yl)p r op ylid e (6g): yield 43%, a pale
brown viscous oil, 1H NMR δ 8.07 (d, 1 H, J ) 8.2), 7.81-7.72
(m, 5 H), 7.50-7.41 (m, 6 H), 7.24 (d, 1 H, J ) 8.5), 4.30, 4.24
(2 br s, 4 H), 3.88 (s, 3 H), 2.59 (s, 6 H); 13C NMR δ 191.8,
191.2, 153.4, 134.8, 134.1, 133.6, 132.2 (7 s), 128.6, 128.1,
128.0, 128.0 (4 d), 128.0 (s), 127.8, 127.6, 127.6 (3 d), 126.0
(s), 125.9, 125.8, 125.7, 125.3, 124.0, 122.0 (6 d), 85.8 (s), 61.8
(q), 48.7, 42.8 (2 t), 26.6 (q); MS m/ z (%) 442 (M+) (1), 380 (8),
285 (6), 271 (10), 243 (14), 169 (57), 141 (100); HRMS Calcd
for C28H26O3S: (M+) 442.16027. Found: (M+) 442.16027.
Dim et h ylsu lfon iu m 1-(2-n a p h t h yla cet yl)-2-oxo-3-(3-
m eth oxy-2-n a p h th yl)p r op ylid e (6h ): yield 54%, a pale
1-P h en yl-5-(p en ta flu or op h en yl)-2,4-p en ta n ed ion e (7e):
yield 93%, mp 55-56 °C; enol form (88%): 1H NMR δ 14.79
(br, OH), 7.37-7.23 (m, 5 H), 5.45 (s, 1 H), 3.70, 3.59 (2 s, 4
H); 13C NMR δ 191.6, 188.5 (2 s), 145.4, 140.6, 137.5 (3 d),
134.7 (s), 129.4, 128.8, 127.3 (3 d), 108.5 (s), 98.8 (d), 43.7, 32.4
(2 t), diketone form (12%): 1H NMR δ 7.32-7.20 (m, 5 H), 3.84,
3.81, 3.70 (3 s, 6 H); 13C NMR δ 201.0, 197.1, 132.9 (3 s), 129.6,
129.1, 127.7 (3 d), 55.2, 50.8, 36.7 (3 t), C6F5 -signals not
detected due to overlapping patterns; MS m/ z (%) 342 (M+)
(4), 251 (100), 181 (60); HRMS Calcd for C17H11F5O2: (M+)
342.06791. Found: (M+) 342.06792.
1
brown viscous oil; H NMR δ 7.82-7.73 (m, 6 H), 7.50-7.41
(m, 3 H), 7.35-7.25 (m, 4 H), 4.63, 4.25 (2 br s, 4 H), 3.90 (s,
3 H), 2.62 (s, 6 H); 13C NMR δ 192.8, 190.9, 155.0, 134.9, 133.8,
133.7, 132.2, 129.3 (8 s), 128.4, 128.4, 127.7, 127.6, 127.6,
127.6, 127.6 (7 d), 126.3 (s), 125.9, 125.4, 123.7, 123.7, 125.2,
113.7 (6 d), 85.9 (s), 56.9 (q), 48.6, 38.6 (2 t), 26.8 (q); MS m/ z
(%) 442 (M+) (1), 301 (10), 171 (100), 141 (88); HRMS Calcd
for C28H26O3S: (M+) 442.16027. Found: (M+) 442.16027.
Syn t h esis of 1,5-Dia r yl-2,4-p en t a n ed ion es 7. To a
stirred suspension of ylide 6 (1.5 mmol) and Zn powder (30
mmol) in 25 mL of CH2Cl2 was added AcOH (30 mmol) at 0
°C, and stirring was continued at rt overnight. The mixture
was filtered through Celite and the filtrate washed with
saturated NaHCO3 and water, eluted with CH2Cl2 through a
short column of Florisil (100-200 mesh), and evaporated. The
crude product was crystallized from methanol.
1,5-Di(1-n a p h th yl)-2,4-p en ta n ed ion e (7f): yield 81%, mp
80-81 °C; enol form (82%): 1H NMR δ 15.29 (br, OH), 7.83-
7.72 (m, 6 H), 7.45-7.39 (m, 4 H), 7.34 (dd, 1 H, J ) 8.2, 7.0),
7.22 (d, 1 H, J ) 6.9), 5.29 (s, 1 H), 3.92 (s, 4 H); 13C NMR δ
192.4, 133.8, 132.0, 131.2 (4 s), 128.7, 128.0, 128.0, 126.3,
125.8, 125.4, 123.8, 99.7 (8 d), 42.5 (t); diketone form (18%):
1H NMR δ 7.85-7.75 (m, 3 H), 7.48-7.37 (m, 4 H), 7.31 (dd,
1 H, J ) 8.2, 7.0), 7.12 (d, 1 H, J ) 7.1), 4.03 (s, 4 H), 3.41 (s,
2 H); 13C NMR δ 202.4, 133.9 132.1, 129.9 (4 s), 128.8, 128.5,
128.3, 126.7, 126.0, 125.5, 123.7 (7 d), 53.8, 48.7 (2 t); MS m/ z
(%) 352 (M+) (12), 211 (44), 183 (16), 168 (18), 141 (100); HRMS
Calcd for C25H20O2: (M+) 352.14633. Found: (M+) 352.14633.

1,5-Diaryl-2,4-pentanediones and -4-methoxy-2-pentanones
J . Org. Chem., Vol. 61, No. 24, 1996 8609
1-(2-Naph th yl)-5-(1-m eth oxy-2-n aph th yl)-2,4-pen tan edi-
on e (7g): yield 86%, a pale yellow viscous oil; enol form: 1H
NMR δ 15.33 (br, OH), 8.13 (d, 1 H, J ) 8.2), 7.88-7.78 (m, 4
H), 7.67 (s, 1 H), 7.60 (d, 1 H, J ) 8.4), 7.59-7.48 (m, 4 H),
7.34 (dd, 1 H, J ) 8.4, 1.7), 7.24 (d, 1 H, J ) 8.5), 5.47 (s, 1 H),
3.80 (s, 3 H), 3.75, 3.63 (2 s, 4 H); 13C NMR δ 193.3, 191.2,
154.1, 134.4, 133.4, 132.5, 132.4, 128.4 (8 s), 128.3, 128.2,
128.1, 128.0, 127.6, 127.6, 127.3, 126.1, 126.1, 126.0, 125.8,
124.2 (12 d), 123.5 (s), 122.1, 99.8 (2 d), 62.1 (q), 44.8, 39.2 (2
t); MS m/ z (%) 382 (M+) (1), 368 (100), 210 (16), 169 (20), 141
(100); HRMS Calcd for C26H22O3: (M+) 382.15689. Found:
(M+) 382.15375.
126.0, 125.7, 123.5, 123.2, 113.0, 99.3 (12 d), 56.2 (q), 44.2,
35.3 (2 t); MS m/ z (%) 382 (M+) (13), 241 (15), 211 (15), 198
(13), 171 (100); HRMS Calcd for C26H22O3: (M+) 382.15689.
Found: (M+) 382.15677.
Ack n ow led gm en t. We would like to thank Mr.
Jukka Knuutinen (Department of Pharmaceutical Chem-
istry, Univ. Kuopio) for obtaining the mass measure-
ments. This work was financially supported by the
Academy of Finland, the Alfred Kordelin Foundation,
and the University of Kuopio Foundation.
1-(2-Naph th yl)-5-(3-m eth oxy-2-n aph th yl)-2,4-pen tan edi-
on e (7h ): yield 58%, mp 122-124 °C; enol form: 1H NMR δ
14.96 (br, OH), 7.80 (d, 1 H, J ) 8.6), 7.76-7.64 (m, 5 H), 7.49
(s, 1 H), 7.43-7.37 (m, 3 H), 7.28 (ddd, 1 H, J ) 8.1, 6.8, 1.1),
7.17 (dd, 1 H, J ) 8.5, 1.8), 7.13 (d, 1 H, J ) 8.9), 5.32 (s, 1H),
4.12 (s, 2 H), 3.69 (s, 3 H), 3.53 (s, 2 H); 13C NMR δ 195.2,
189.5, 154.8, 133.4, 133.3, 132.6, 132.3 (7 s), 129.1 (d), 129.1
(s), 128.4 (d), 128.3 (s), 128.1, 127.9, 127.6, 127.6, 126.4, 126.8,
Su p p or tin g In for m a tion Ava ila ble: Discussion of spec-
tral data and copies of 13C NMR spectra (38 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
J O960887A