Synthesis and cyclization of 1-(2-hydroxyphenyl)-2-propen-1-one epoxides: 3-Hydroxychromanones and -flavanones versus 2-(1-hydroxyalkyl)-3-coumaranones

Article abstract of DOI:10.1021/jo960163z

Competitive α and β cyclization of 2'-hydroxychalcone epoxides affords 2-(α-hydroxybenzyl)-3-coumaranone and/or 3-hydroxyflavanones, which depends on the conditions employed. Epoxidation of 2'-hydroxychalcones by dimethyldioxirane followed by either base- or acid-catalyzed ring closure provides a novel, general, and efficient method for the synthesis of trans-3-hydroxyflavanones, which includes also the naturally occurring derivatives. Extension of this two-step procedure to 1-(2-hydroxyphenyl)-2-alken-1-ones was also accomplished. A strong preference for α cyclization was observed in the case of β-unsubstituted or -monoalkylated α,β-enones, while both 2,2-dimethyl-3-hydroxychromanones and 2-(1-hydroxy-1-methylethyl)-3-coumaranones were obtained from the β,β-dimethylated substrates.

Full text of DOI:10.1021/jo960163z

J . Org. Chem. 1996, 61, 5375-5383
5375
Syn th esis a n d Cycliza tion of 1-(2-Hyd r oxyp h en yl)-2-p r op en -1-on e
Ep oxid es: 3-Hyd r oxych r om a n on es a n d -fla va n on es ver su s
2-(1-Hyd r oxya lk yl)-3-cou m a r a n on es
Tama´s Patonay,* Albert Le´vai, and Csaba Nemes
Department of Organic Chemistry, Kossuth Lajos University, H-4010 Debrecen, Hungary
Tibor Tima´r
Alkaloida Chemical Company, Ltd, H-4440 Tiszavasva´ri, Hungary
Ga´bor To´th
Technical Analytical Research Group of the Hungarian Academy of Sciences, Institute for General and
Analytical Chemistry, Technical University, H-1111 Budapest, Hungary
Waldemar Adam*
Institute of Organic Chemistry, University of Wu¨rzburg, Am Hubland, D-97074 Wu¨rzburg, Germany
Received J anuary 25, 1996X
Competitive R and â cyclization of 2′-hydroxychalcone epoxides affords 2-(R-hydroxybenzyl)-3-
coumaranone and/or 3-hydroxyflavanones, which depends on the conditions employed. Epoxidation
of 2′-hydroxychalcones by dimethyldioxirane followed by either base- or acid-catalyzed ring closure
provides a novel, general, and efficient method for the synthesis of trans-3-hydroxyflavanones, which
includes also the naturally occurring derivatives. Extension of this two-step procedure to 1-(2-
hydroxyphenyl)-2-alken-1-ones was also accomplished. A strong preference for R cyclization was
observed in the case of â-unsubstituted or -monoalkylated R,â-enones, while both 2,2-dimethyl-3-
hydroxychromanones and 2-(1-hydroxy-1-methylethyl)-3-coumaranones were obtained from the â,â-
dimethylated substrates.
In tr od u ction
bromohydrins (Rasoda reaction),5 or simultaneous depro-
tection and ring-closure of 2′-hydroxy-protected chalcone
epoxides.6,7 Common limiting factors of these methods
entail side reactions, strong solvent, temperature, and
substitution pattern dependence. Very recently a highly
diastereoselective oxidation of enolate derivatives of
flavanone by dimethyldioxirane (DMD) to trans-3-hy-
droxyflavanones as major diastereomer has also been
reported.8
2′-Hydroxychalcone epoxides have been postulated9 as
intermediates in the Algar-Flynn-Oyamada reaction,
although their role in the formation of 3-hydroxyfla-
vanones was strongly disputed.4,6 Their intermediacy
was also proposed in the Rasoda reaction.5c For a long
time the parent compound, 2′-hydroxychalcone epoxide,
was the only known representative of the family, pre-
pared in low yield by m-chloroperbenzoic acid (mCPBA)
oxidation of 2′-hydroxychalcone.10,11 A few years ago we
reported12 a general and high-yield synthesis of these
trans-3-Hydroxyflavanones (trans-2,3-dihydro-2-aryl-
3-hydroxy-4H-1-benzopyran-4-ones) and their 3-O-sub-
stituted derivatives are important intermediates in the
synthesis of a wide variety of flavonoid compounds and
also play a significant role in the biogenesis of naturally
occurring flavonoid-type derivatives.1 Some of these
show considerable biological activity;2 among others
silybin and related flavanolignans are marketed as
hepatoprotective agents.3
A great number of synthetic methods have been
developed,1 which include alkaline hydrogen peroxide
oxidation of 2′-hydroxychalcones4 (called the Algar-
Flynn-Oyamada reaction in flavonoid chemistry), base-
induced cyclization of 2′-hydroxychalcone dibromides and
X Abstract published in Advance ACS Abstracts, J uly 1, 1996.
(1) For monographs and reviews see: (a) Geissman, T. A. The
Chemistry of Flavonoid Compounds; Pergamon: Oxford, 1962. (b) The
Flavonoids; Harborne, J . B.; Mabry, T. J .; Mabry, J ., Eds.; Chapman
& Hall: London, 1975. (c) The Flavonoids: Advances in Research since
1980; Harborne, J . B., Ed.; Chapman & Hall: London, 1988. (d)
Patonay, T. Trends Heterocycl. Chem. 1993, 3, 421.
(2) For monographs and reviews see: (a) Bo¨hm, K. Die Flavonoide:
Eine U¨ bersicht u¨ber ihre Physiologie, Pharmakodynamik und thera-
peutische Verwendung; Cantor: Aulendorf, 1967. (b) Parmar, N. S.;
Ghosh, M. N. Indian J . Pharmacol. 1980, 12, 213. (c) Havsteen, B.
Biochem. Pharmacol. 1983, 32, 1141. (d) Ga´bor, M. The Pharmacology
of Benzopyran Derivatives and Related Compounds; Akade´miai Kia-
do´: Budapest, 1988.
(5) (a) Marathey, M. G. J . Org. Chem. 1955, 20, 563. (b) Kelkar, A.
S.; Kulkarni, A. B. Indian J . Chem. 1973, 11, 726. (c) Donnelly, J . A.;
Fox, M. J .; Sharma, T. C. Tetrahedron 1979, 35, 1987.
(6) Litkei, G. In Recent Developments in the Chemistry of Natural
Carbon Compounds, Vol. 9; Bogna´r, R.; Bruckner, V.; Sza´ntay, Cs.,
Eds.; Akade´miai Kiado´: Budapest, 1979; pp 293-408.
(7) (a) Onda, M.; Li, S. S.; Li, X.; Harigaya, H.; Takahashi, H.;
Kawase, H.; Kagawa, H. J . Nat. Prod. 1989, 52, 1100 and the earlier
part of the series. (b) Augustyn, J . A. N.; Bezuidenhoudt, B. C. B.;
Ferreira, D. Tetrahedron 1990, 46, 2651.
(3) (a) Vogel, G. Arzneim.-Forsch. 1968, 18, 1063. (b) Cavallini, L.;
Luchetti, G. Gazz. Med. Ital. 1976, 125, 365.
(8) Adam, W.; Mu¨ller, M.; Prechtl, F. J . Org. Chem. 1994, 59, 2358.
(9) Fukushima, D. K.; Geissman, T. A. J . Am. Chem. Soc. 1948, 70,
1686.
(10) Kagan, J ., Ramakrishnan, V. T. J . Org. Chem. 1970, 35, 2898.
(11) Old, K. B.; Main, L. Tetrahedron Lett. 1977, 2809.
(12) (a) Adam, W.; Hadjiarapoglou, L.; Smerz, A. Chem. Ber. 1991,
124, 227. (b) Adam, W.: Bialas, Hadjiarapoglou, L.; Patonay, T.
Synthesis 1992, 49.
(4) (a) Cummins, B.; Donnelly, D. M. X.; Eades, J . F.; Fletcher, H.;
O’Cinneide, F.; Philbin, E. M.; Swirski, J .; Wheeler, T. S.; Wilson, R.
K. Tetrahedron 1963, 19, 499. (b) Dean, F. M.; Podimuang, V. J . Chem.
Soc. 1965, 3978. (c) Gormley, T. R.; O’Sullivan, W. I. Tetrahedron 1973,
29, 369. (d) Saxena, S.; Makrandi, J . K.; Grover, S. K. Synthesis 1985,
110 and the references cited therein.
S0022-3263(96)00163-6 CCC: $12.00 © 1996 American Chemical Society

5376 J . Org. Chem., Vol. 61, No. 16, 1996
Ta ble 1. Cycliza tion of 2′-Hyd r oxych a lcon e Ep oxid e (2a )a
product composition (%)c
Patonay et al.
entry
reagentb
solvent
time
2a
trans-3a
cis-3a
4a d
5a
6
7
1e
2
3
4
5
-
EtOH-H2O (95:5, v/v)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2-H2O (97:3, v/v)
H2O
EtOH-H2O (1:1, v/v)
9 h
24 h
25 h
1 h
2 min
5 min
2.75 h
2.75 h
18
19
49
0
7
0
55
35
24
39
40
74
82
>95
0
0
0
0
2
5
0
0
14 (40:60)
43 (43:57)
21 (26:74)
15 (40:60)
44 (48:52)
0 (-)
0
3
12
10
4
8
0
0
13
0
1
36
3
12
0
3
0
4
6
3
0
0
0
TEA
DMAP
DBU
DBU
TBAH
HClO4 (0.01 M)
HCl (0.12 M)
6
7f,g
8
5
0
0 (-)
0 (-)
0
a
Reactions were performed at room temperature (20 °C) unless otherwise stated, 0.25 equiv of base was added in entries 2-6.
b
Abbrevations used: TEA: triethylamine, DMAP: 4-(dimethylamino)pyridine, DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene, TBAH: tet-
rabutylammonium hydroxide. c Product ratios were determined by 1H NMR spectroscopy. In parentheses is given the erythro/ threo
d
ratio. e Performed at reflux temperature f Performed at 55 °C. Also 2,3-dihydroxy-1-(2-hydroxyphenyl)-3-phenyl-1-propanone (13%) was
g
also formed.
epoxides directly from chalcones without protection of the
phenolic hydroxy functionality by using DMD.13 Parallel
to our work, Adams and Main14 developed a multistep
methodology for the synthesis of 2′-hydroxychalcone
epoxides based on the selective deprotection of tetrahy-
dropyranylated derivatives, but their protocol was limited
to 6′-substituted compounds without electron-releasing
substituent at C-4. The efficiency and convenience of the
dimethyldioxirane route12 prompted us to investigate the
cyclization of 2′-hydroxychalcone epoxides in the interest
of providing a new and general synthetic method for the
preparation of 3-hydroxyflavanones, the feasibility of
which was demonstrated in a preliminary communica-
tion.15 We now report in detail our results on the
cyclization of 2′-hydroxychalcone epoxides and the ex-
ploitation of this reaction for the synthesis of various
trans-3-hydroxyflavanones.
Resu lts a n d Discu ssion
Cyclization of 2′-hydroxychalcone epoxide (2a ) to trans-
3-hydroxyflavanone (trans-3a ) has already been reported
in the very first papers,10,11 but somewhat controversial
data were published on its stability. To survey the
reaction paths and to optimize the cyclization conditions,
epoxide 2a was synthesized by using DMD according to
the literature procedure12a and was allowed to react with
various reagents. The reaction mixture was analyzed by
1H NMR spectroscopy and the product data are sum-
marized in Table 1.
The results clearly show that, in contrast with previous
claims,11 epoxide 2a is remarkably stable. In an etha-
nol-water mixture at elevated temperature (Table 1,
entry 1) or in the presence of weaker bases such as
triethylamine (Table 1, entry 2) or 4-(dimethylamino)-
pyridine (Table 1, entry 3), considerable amounts of
unreacted starting material 2a could be detected even
after a prolonged reaction period. This contradicts the
half-life of 2.5 s (for pH 7) reported11 earlier, although
this value refers to aqueous, buffered condions. Another
important finding is that under basic or even neutral
conditions not only â cyclization to trans-3a but also R
cyclization to 2-(R-hydroxybenzyl)-3-coumaranone (4a )
takes place (Scheme 1).
Similar competitive pathways were found18 and kineti-
cally analyzed in the cyclization of 6′-alkoxy-2′-hydroxy-
chalcone epoxides, but exclusive â cyclization was pro-
posed for 6′-unsubstituted species, such as epoxide 2a .
In our preparative scale experiment coumaranone 4a was
isolated as a mixture of erythro and threo diastereomers
by silica gel chromatography and fully characterized by
spectroscopic methods and elemental analysis.
The 1H and 13C NMR spectra of the mixture of 4a
diastereomers displayed two series of signals with dif-
ferent intensities, which allowed easy differentiation of
the two isomers. These diastereomers were characterized
In contrast with the widely studied 3-hydroxyfla-
vanones, much less has been published on the synthesis
of the related 3-hydroxychromanones (2,3-dihydro-3-
hydroxy-4H-1-benzopyran-4-ones). Although the 3-hy-
droxychromanone skeleton is also a frequent structural
unit of various natural products,16 only a few synthetic
methods have hitherto been developed. Lead tetraac-
etate-mediated acetoxylation of chromanones17 offers a
useful approach but occasional difficulties in the hydroly-
sis of the resulting 3-acetoxychromanones have been
reported.17a A more elegant and enantioselective hy-
droxylation of 3-substituted chromanone enolates by
sulfonyloxaziridines was published recently by Davis and
co-workers.16 The above-mentioned ease of the prepara-
tion of chalcone epoxides and their successful cyclization
encouraged us to extend our investigations to the DMD
oxidation of other 1-(2-hydroxyphenyl)-2-propen-1-ones
without an aryl moiety at C-3, which provides a new and
useful access to 3-hydroxychromanones.
3
by their J (2-H, R-H) coupling constants, namely 2.7 Hz
(13) (a) Adam, W.; Curci, R.; Edwards, J . O. Acc. Chem. Res. 1989,
22, 205. (b) Murray, R. W. Chem. Rev. 1989, 89, 1187; (c) Adam, W.;
Curci, R.; Hadjiarapoglou, L.; Mello, R. In Organic Peroxides; Ando,
W., Ed.; Wiley: New York, 1992; pp 195-219. (d) Adam, W.; Hadji-
arapoglou, L. Topics Curr. Chem. 1993, 164, 45. (e) Curci, R.; Dinoi,
A.; Rubino, M. F. Pure Appl. Chem. 1995, 67, 811.
(14) Adams, C. J .; Main, L. Tetrahedron 1991, 47, 4959.
(15) Patonay, T.; To´th, G.; Adam, W. Tetrahedron Lett. 1993, 34,
5055.
(16) (a) Davis, F. A.; Weismiller, M. C. J . Org. Chem. 1990, 55, 3715.
(b) Davis, F. A.; Chen, B. C. Tetrahedron Lett. 1990, 31, 6823.
(17) (a) Cavill, G. W. K.; Dean, F. M.; McGookin, A.; Marshall, B.
M.; Robertson, A. J . Chem. Soc. 1954, 4573. (b) Russel, G. A.;
Blankespoor, R. L.; Trahanovsky, K. D.; Chung, C. S. C.; Whittle, P.
R.; Mattox, J .; Penny, R.; Ku, T.; Kosugi, Y.; Givens, R. S. J . Am. Chem.
Soc. 1975, 97, 1906.
for the major and 6.4 Hz for the minor isomer. These
values are in good agreement with the coupling constants
(2.4 and 6.3 Hz) reported for the erythro,threo pair of 2-(R-
hydroxybenzyl)-4-methoxy-3-coumaranone by Adams and
Main,18a who assigned the diastereomer with the smaller
3J (2-H, R-H) coupling constant to the threo isomer. Their
assignment is based on the postulated existence of one
exclusive conformation for each isomer, which is fixed by
intramolecular hydrogen bonding between the R-hydroxyl
(18) (a) Adams, C. J .; Main, L. Tetrahedron 1991, 47, 4979. (b) Ibid.
1992, 48, 9929.

1-(2-Hydroxyphenyl)-2-propen-1-one Epoxides
J . Org. Chem., Vol. 61, No. 16, 1996 5377
Sch em e 1
and the carbonyl oxygen. However, in the spectra of the
4a isomers, neither the OsH and CdO stretchings (νOH
3460 and νCO 1712 cm-1) nor the chemical shifts of the
R-hydroxy protons (δ ) 3.68 for the minor and δ ) 2.84
ppm for the major isomer) indicate the existence of any
strong hydrogen bonding. On the basis of the somewhat
higher chemical shift value for the major isomer (∆δ )
0.84 ppm), weak bonding between the hydroxyl group and
the carbonyl oxygen or O-1 ether oxygen may be as-
sumed. Therefore, we deemed it necessary to search for
additional NMR evidence to assign the stereochemistry
unambiguously.
of 3J (2-H, R-H) constant. For this differentiation the
3
vicinal J (H,C) coupling constants between the 2-H and
R-H protons were determined by the 2D semiselective
INEPT method.19 On the basis of the Karplus-type
dependence of 3J (H,C) on the dihedral angle, the observed
3
3
values of 1.8 Hz for both J (R-H, C-3) and J (2-H, C-1′)
strongly support conformer threo-B since the antiperipla-
nar position of these atoms in conformer threo-A should
give coupling constants of ca. 7-8 Hz. We conclude that
the major diastereomer of 4a with the characteristic
coupling constant 3J (2-H, R-H) of 2.7 Hz is the threo
isomer with dominance of the threo-B conformer. More-
over, on the basis of our earlier studies,20 the value of
For erythro- and threo-4a , the equilibrium of the
following conformers A, B, and C may be considered.
3
4.0 Hz for the coupling constant J (R-H, C-2′,6′) suggests
a dihedral angle of ca. 30° between the HR-CR bond and
the plane of the phenyl ring.
On the basis of coupling constant 3J (2-H, R-H) of 6.4
Hz measured for the minor diastereomer of 4a , we can
conclude that both conformers erythro-A and erythro-B
are extensively populated in the conformational equilib-
rium. The previously postulated weak hydrogen bonding
for this diastereomer is in agreement with both these
conformations as well as the observed 3J (R-H, C-3)
coupling constant of 1.9 Hz. The marked increase (∆J
3
) 2.0 Hz) of J (2-H, C-1′) coupling constant of 3.8 Hz
compared to that of threo-4a isomer shows unequivocally
the increased population of conformer erythro-A in which
C-1′ and 2-H atoms are located in the antiperiplanar
position.
Irreversible formation of the 3-hydroxyflavanone (trans-
3a ) was verified by a control experiment. Due to the
trans stereochemistry of the oxirane ring opening, the
primary product in the R cyclization of 2′-hydroxychal-
cone epoxide (2a ) is the erythro-4a , which equilibrates
with its threo-4a diastereomer by the deprotonation-
enolization-reprotonation sequence.18a,21 Besides the
flavanone trans-3a and the isomeric coumaranones 4a
formed in the cyclization step, a number of secondary
Significant populations of both the threo-C and eryth-
ro-C can be excluded on the basis of the unfavorable
steric interaction between the carbonyl and phenyl
groups. Since the conformer threo-A also suffers from
steric crowding of the phenyl group and the C-3 and O-1
atoms, the conformer B is expected to dominate one for
the threo-4a isomer. Furthermore, to the conformer
threo-C, a coupling constant of 10-12 Hz would be
expected between 2-H and R-H protons; thus, the mea-
sured low value (2.7 Hz) also supports the low population
of this conformer. However, the same dihedral angle (ca.
60°) of 2-H and R-H in both threo-A and threo-B does not
allow these conformers to be distinguished on the basis
(19) J ippo, T.; Kamo, O.; Nagayama, K. J . Magn. Reson. 1986, 66,
344.
(20) To´th, G.; Le´vai, A.; Duddeck, H. Magn. Reson. Chem. 1992, 30,
325.
(21) Wong, E. Phytochemistry 1967, 6, 1227.

5378 J . Org. Chem., Vol. 61, No. 16, 1996
Patonay et al.
Sch em e 2
which the product data (Table 1, entries 7, 8) revealed
almost exclusive â cyclization. This advantage may be
rationalized in terms of a change in the mechanism of
the ring closure. In contrast with the attack of a
phenolate anion on the oxirane ring under basic or
neutral conditions (SN2 mechanism), in the presence of
strong acids the attack of the phenolic hydroxy group
occurs on a protonated epoxide (SN1-like mechanism).
Thus, the â carbon atom of this protonated intermediate
possesses considerable cationic character at the resonance-
stabilized benzylic position and, therefore, the more
pronounced reactivity at this position.
This enhanced regioselectivity was utilized syntheti-
cally by replacing the second step of the former base-
catalyzed protocol (method A) by acid treatment (method
B). Comparison of yields collected in Table 2 establishes
the superiority of the acid-catalyzed cyclization. Incor-
poration of electron-withdrawing R1 groups in the C-4
position (Table 2, entries 8, 9) required longer reaction
times for the acid-catalyzed cyclization, which is in
agreement with the destabilization of the protonated
species D.
products thereof were also observed. Thus, the cis-3-
hydroxyflavanone (cis-3a ) derived from the trans-3a by
base-catalyzed epimerization in the presence of strong
bases (Table 1, entries 5, 6), and 3-hydroxyflavone (5a ),
the product from trans-3a by dehydrogenation in the
basic medium in the presence of air,10 were obtained as
well (Scheme 2, Table 1, entries 2-6). 3-Coumaranone
(6) and benzaldehyde (7), which are the products of the
retro aldol cleavage of erythro,threo-4a , were also de-
tected.
The significant shift in the product ratio in favor of
the retro aldol products 6 and 7 (Table 1, entries 4, 5) in
the DBU-catalyzed transformations at the longer reaction
time clearly confirms this cleavage. Adams and Main18
have also observed the formation of 4-methoxycoumara-
none during the cyclization of 2′-hydroxy-6′-methoxy-
chalcone epoxide under strongly basic conditions.
We also tested basic ion-exchange resins such as
Amberlyst 21 or Amberlite IRA410 (OH- form) to produce
the cyclization but, surprisingly, no reaction took place
at all. On the other hand, the use of tetrabutylammo-
nium hydroxide (TBAH) (Table 1, entry 6) resulted in a
slight shift in the competitive primary reactions in favor
of â cyclization and in the fast and complete retro aldol
cleavage of the coumaranone 4a . These advantageous
changes were exploited to develop a new and general two-
step procedure for the synthesis of trans-3-hydroxyfla-
vanones 3. In the first step, the 2′-hydroxychalcones 1a -
d ,g-i were oxidized with DMD (as acetone solution)22
and after removal of the solvent, the crude epoxides 2a -
d ,g-i were treated with TBAH (0.3 equiv) in dichlo-
romethane-water mixture as medium to give the desired
trans-3-hydroxyflavanones 3a -d ,g-i in good overall
yield (Scheme 1, Table 2, method A).
The determining role of the stabilizing/destabilizing
effect of ring B substituents on the rate of cyclization was
also utilized for the synthesis of naturally occurring
trans-3-hydroxyflavanones 3. The common feature of
these derivatives is that most of them have at least one
but typically two or three hydroxy or alkoxy functional-
ities on the aromatic ring attached to the C-2. Due to
the activating effect of the electron-donating hydroxy
groups, when 2′,4′,3,4-tetrahydroxychalcone or butein (1j)
was treated with DMD, the corresponding trans-3,7,3′,4′-
tetrahydroxyflavanone or (()-fustin1a (trans-3j) was ob-
tained directly in 50% yield. Besides 3j, only highly
polar, colored products with low Rf values could be
detected by TLC. The probable side reaction, which
lowered the yield of 3j, is the formation of quinone-type
derivatives23 from both the starting material 1j and the
cyclization product trans-3j. In spite of this drawback,
the direct DMD oxidation offers an exceptionally simple
and efficient method for the preparation of naturally
occurring polyhydroxylated 3-hydroxyflavanones.
The synthesis of natural 3-hydroxyflavanones with less
activating substituents in their ring B was accomplished
by using protecting groups. To demonstrate this ap-
proach, methoxymethylated trans-3i, synthesized either
by the method A or B (Table 2, entries 14, 15), was
deprotected to the trans-3,7-dihydroxy-3′,4′-ethylene-
dioxyflavanone (trans-3k ), a model compound of silybin
and its derivative (Scheme 3).
The main advantage of this methodology over the
previous syntheses is that the yield of isolated product
trans-3 is independent of the substitution pattern for a
wide range of substituents. The only factor which limits
the yield of the flavanones trans-3 is the competitive R
cyclization.
As a logical extension, we also examined the oxidation
of R,â-unsaturated ketones without an aryl group at the
â position to assess whether 3-hydroxychromanones and/
or 2-(1-hydroxyalkyl)-3-coumaranones are formed. Sur-
prisingly little has been published in this area so far, e.g.
The possibility for further improvement was offered by
the cyclization of epoxides 2 under acidic conditions, for
(22) Adam, W.; Bialas, J .; Hadjiarapoglou, L. Chem. Ber. 1991, 124,
2377.
(23) Crandall, J . K.; Zucco, M.; Kirsch, R. S.; Coppert, D. M.
Tetrahedron Lett. 1991, 32, 5441.

1-(2-Hydroxyphenyl)-2-propen-1-one Epoxides
J . Org. Chem., Vol. 61, No. 16, 1996 5379
Ta ble 2. Syn th esis of 3-Hyd r oxyfla va n on es tr a n s-3
entry
trans-3
R1
R2
R3
H
R4
methoda
DMD (equiv)
yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
a
H
H
H
H
H
A
B
A
B
A
B
A
B
B
A
B
A
B
A
B
h
6.1
6.8
3.6
3.2
2.4
3.6
4.8
6.5
16.5d
7.2
8.5
4.4
6.5
4.8
4.9
4.0
-
55
67
44
67
51
57c
47
72
53e,f
53
72
40
57g
44
36
50
76
b
c
Me
H
H
H
H
OMe
d
e
f
F
H
H
H
H
H
H
H
Cl
H
H
H
H
Br
CN
H
g
h
i
H
H
H
H
Me
OCH2CH2O
OCH2OMe
j
k
OH
OH
H
H
OH
OH
OCH2CH2O
h
a
Method A: 1. DMD/CH2Cl2-Me2CO/0 °C, 2. TBAH (0.3 equiv)/CH2Cl2-H2O/rt (ca. 20 °C); method B: 1. DMD/CH2Cl2-Me2CO/0
°C, 2. 0.12 M HCl-EtOH (1:1, v/v)/rt (ca. 20 °C) Yields refer to isolated pure products. c Also 3-hydroxy-4′-methoxyflavone (5c) was
b
isolated, 16%, mp 235-237 °C (lit.40 mp 236 °C). Extent of epoxidation was ca. 78% on the basis of 1H NMR of the crude epoxide.
d
e Cyclization was performed at reflux temperature, no reaction occurred at room temperature (ca. 20 °C). f Yield corrected for the extent
g
h
of conversion. Small amount of unreacted chalcone 1h was also detected by TLC. See text.
Sch em e 3
Treatment of the propenones 8a -e with DMD (Table 3,
entries 2-5 and 8) revealed that the epoxides 9a -e are
much more labile than the corresponding chalcone ep-
oxides 2. TLC monitoring showed a component with
intermediate character but only the cyclization products
10 and 11 were isolated after workup and column
chromatography (Scheme 4).
The yield data in Table 3 establish that R cyclization
dominates to afford 2-(1-hydroxyalkyl)-3-coumaranones
11a ,b in the case of substrates 8a ,b, which are unsub-
stituted or monosubstituted at carbon â. On the con-
trary, the dimethyl enones 8c-e furnish both the cou-
maranones30 11c-e and 2,2-dimethyl-3-hydroxychrom-
anones 10c-e, for which the regioselectivity is usually
low with a slight preference of â cyclization. A possible
explanation for this trend is that the incorporation of
alkyl groups increases the stability of the partially
positively charged carbon â in the transition state of â
cyclization. On the basis of yield data in Table 3, we can
conclude that the epoxide route has synthetic value only
for the preparation of 2,2-dialkylated 3-hydroxychro-
manones.
1-(2,5-Dihydroxy-4-methoxyphenyl)-3-methyl-2-buten-
1-one (12d ), an interesting byproduct hydroxylated in its
aromatic moiety, was also isolated from the dioxirane
oxidation of enone 8d (Table 3, entry 5). Such aromatic
hydroxylation has already been reported in the prepara-
tion of hydroquinones31 or methoxybenzenes from their
p-methoxyphenol intermediates,32 but this is the first
example to proceed in competition with alkene oxidation.
No hydroxylation-type product 12 was observed in the
DMD oxidation of substrates 8a -c,e. This difference
indicates that both the presence of the activating 4′-
methoxy group and the trisubstituted double bond is a
prerequisite for the formation of the arene epoxide
intermediate 13 (Scheme 4).
Donnelly and Maloney24 reported the failure of the
oxidation of 8a with alkaline hydrogen peroxide in
methanolic medium because of the greater propensity of
the substrate for conjugate addition of methanol. In the
presence of a weaker base such as potassium carbonate,
the desired 3-hydroxychromanone (10a ) was obtained in
poor yield (6.4%) beside catechol as the major product,
which was generated by the concurrent Baeyer-Villiger
reaction. On the contrary, 1-(2-hydroxy-4,6-dimethoxy-
phenyl)-2-propen-1-one failed to react under the same
conditions.
As starting materials 8a ,b,d ,f were prepared by lit-
erature methods,25-28 the 6-tosyloxy derivative 8e was
obtained by tosylation of 8f. The parent dimethyl deriva-
tive 8c was isolated as a byproduct of the Fries rear-
rangement29 of phenyl 3-methylcrotonate in low yield.
(24) Donnelly, J . A.; Maloney, D. E. Tetrahedron 1979, 35, 2883.
(25) Turbina, A. I.; Sinyavskii, V. G. Metody Poluch. Khim. Reakt.
Prep. 1964, 86; Chem. Abstr. 1966, 65, 8807g.
(26) Miranda, M. A.; Primo, J .; Tormos, R. Heterocycles 1988, 27,
673.
(27) Tima´r, T.; Hosztafi, S.; J a´szbere´nyi, J . Cs.; Ko¨ve´r, K. E.; Batta,
Gy. Acta Chim. Hung. 1988, 125, 303.
(28) Sebo¨k, P.; J eko¨, J .; Tima´r, T.; J a´szbere´nyi, J . Cs. Heterocycles
1994, 38, 2099.
(29) Baker, W.; Floyd, A. J .; McOmie, J . F. W.; Pope, G.; Weaving,
A. S.; Wild, J . H. J . Chem. Soc. 1956, 2010.
(30) The only example of this family that appears to be reported5c
previously is the 7-bromo-4,6-dimethoxy-2-(1-hydroxy-1-methylethyl)-
2-coumaranone, which was isolated from the reaction of 2′-acetoxy-3′-
bromo-4′,6′-dimethoxychalcone epoxide with sodium hydroxide in
aqueous acetone. The pathway postulated by the authors involves an
R cyclization of the chalcone epoxide, a subsequent retro aldol cleavage
of the 2-(R-hydroxybenzyl)-3-coumaranone (vide supra) and attack of
the ketone solvent on the coumaranone enolate.
(31) Altamura, A.; Fusco, C.; D’Accolti, L.; Mello, R.; Prencipe, T.;
Curci, R. Tetrahedron Lett. 1991, 32, 5445.
(32) Adam, W.; Shimizu, M. Synthesis 1994, 560.

5380 J . Org. Chem., Vol. 61, No. 16, 1996
Ta ble 3. Oxid a tion of 1-(2-Hyd r oxyp h en yl)-2-p r op en -1-on es 8
Patonay et al.
yielda (%)
substrate
entry
R1
H
R2
R3
amount (mmol)
oxidant [equiv]
conversion (%)
10
11
12
1b
2
3
4
5
6
7
8
a
H
H
18.9
2.50
2.00
2.04
2.00
2.25
2.25
0.78
H2O2/K2CO3 [1.3]
DMD [3.6]
DMD [6.3]
DMD [5.2]
DMD [5.3]
H2O2-NaOH [2.75]
mCPBA [3.3]
DMD [10.1]
100
100
84
84
83
100
88
81
6.4
5.1
4.9
0
0
0
0
0
7.3
0
9.8
0
53
b
c
d
Me
Me
Me
H
Me
Me
MeO
H
MeO
37c
31
47
26
48
33
68
5.6
7.2
27
17
e
Me
Me
TsO
a
b
Yields refer to isolated products and are corrected for the extent of conversion. Data from ref 24; also catechol (32%) was isolated.
c As a 3:2 mixture of erythro and threo diastereomers.
Sch em e 4
(50 MHz) spectra were recorded in CDCl3 solution with TMS
as internal reference unless otherwise stated. EI mass spectra
were run at 70 eV. All commercial reagents were used as
purchased. MgSO4 served as drying agent. TLC’s were
developed on Kieselgel 60 F254 sheets (Merck), column chro-
matography was performed on silica gel 60 (0.063-0.2 mm).
The 2′-hydroxychalcones 1 were synthesized according to
literature procedures.33 Dimethyldioxirane (DMD) (0.08-0.1
M acetone solution) was prepared as described in the litera-
ture22 and its peroxide content was determined by iodometric
titration. DMD solutions were stored over molecular sieve (4
Å) at -20 °C.
The oxidation of enone 8d by other oxidants such as
alkaline hydrogen peroxide (Table 3, entry 6) and
mCPBA (Table 3, entry 7) revealed that in comparison
with derivative 8a , dimethyl substitution of the â carbon
lowers its reactivity for the conjugate addition of the
solvent methanol under basic conditions and allows the
synthesis of 3-hydroxychromanone. mCPBA was found
to react very sluggishly and yielded also a considerable
amount of the hydroxylated product 12d , presumably
through the epoxide 13 (Scheme 4). Previously the
oxidation of the 2′-hydroxy-4′,6′-dimethoxychalcone to the
2′,5′-dihydroxy-4′,6′-dimethoxychalcone was reported24 in
7.6% yield upon treatment with mCPBA, which supports
the electrophilic arene oxide for the aromatic hydroxyl-
ation of activated substrates.
In summary, 1-(2-hydroxyphenyl)-2-alken-1-one ep-
oxides, available by DMD oxidation of the corresponding
enones, are useful intermediates for the synthesis of
3-hydroxychromanones and 2-(1-hydroxyalkyl)-2-couma-
ranones in good yield. The formation of coumaranones
by R cyclization is a general pathway in the ring closure
of these epoxides although its participation strongly
depends on the substitution of the â carbon and on the
oxidation conditions.
Cyclization of 2′-Hydr oxych alcon e Epoxide (2a). Ch ar -
a cter iza tion of P r od u cts a n d Deter m in a tion of P r od u ct
Ra tios. 2′-Hydroxychalcone epoxide (2a )12a (112 mg, 0.50
mmol) was treated with the reagents and under the conditions
given in Table 1. The reaction mixture was poured into water
(50 mL), extracted with CH2Cl2 (3 × 15 mL), and dried. The
solvent was removed under reduced pressure, and the com-
1
position of the residue was determined by means of H NMR
spectroscopy. For characterization of the major products trans-
3a , erythro- and threo-4a , pure analytical samples were
obtained from the reaction mixture of entry 5 (started from
3.00 mmol of 2a ) by column chromatography (eluent: hexane-
acetone ) 4:1, v/v). Yields of isolated materials were 43% for
trans-3a and 20% for erythro,threo-4a (as a mixture of dia-
stereomers).
tr a n s-3-Hyd r oxyfla va n on e (tr a n s-3a ): mp 186-190 °C
(lit.34 mp 183-184 °C, lit.35 mp 188 °C), colorless needles. 1H
Exp er im en ta l Section
(33) Dhar, D. N. The Chemistry of Chalcones and Related Com-
pounds; Wiley: New York,1981.
(34) Oyamada, T. Bull. Chem. Soc. J pn. 1941, 16, 411; Chem. Abstr.
1947, 41, 3797.
Gen er a l. Melting points were determined with a Boetius
hot-stage apparatus and are uncorrected. Elemental analysis
were performed in-house. IR spectra were measured for KBr
discs unless otherwise specified. 1H (200 MHz) and 13C NMR
(35) Eneba¨ck, C.; Gripenberg, J . Acta Chem. Scand. 1957, 11, 866.

1-(2-Hydroxyphenyl)-2-propen-1-one Epoxides
J . Org. Chem., Vol. 61, No. 16, 1996 5381
NMR δ 7.94 (dd, J ) 7.6, 1.9 Hz, 1H), 7.40-7.62 (m, 6H), 7.0-
7.15 (m, 2H), 5.16 (d, J ) 12.4 Hz, 1H), 4.66 (d, J ) 12.4 Hz,
1H), 3.67 (s, 1H, D2O exchangeable).
dried, and concentrated. The residue was treated with cold
hexane-absolute EtOH or hexane-acetone mixture (10-20:
1, v/v), and the solid crystalline residue was collected to give
1
pure trans-2 (>95% by H NMR).
er yt h r o,t h r eo-2-(r-H yd r oxyb e n zyl)-3-cou m a r a n on e
(er yth r o,th r eo-4a ): Yellow oil. IR (neat) 3436, 2924, 1712,
1612, 1460, 1322, 1192, 1144, 1124, 1102, 1070, 1048, 1022,
tr a n s-3-H yd r oxyfla va n on e (tr a n s-2a ): Yields: 55%
(method A, stirring period: 5 min), 67% (method B, stirring
period: 2.5 h); mp 188-191 °C (lit.34 mp 183-184 °C, lit.35
mp 188 °C), colorless needles.
880, 758, 698 cm-1
.
MS (m/z, rel int): 240 (M+., 22%), 238
(4), 222 (74), 221 (16), 220 (17.5), 195 (7), 183 (3), 165 (4.5),
134 (100), 121 (13), 105 (51), 91 (7), 79 (19), 77 (32). Anal.
Calcd for C15H12O3 (240.26): C, 74.99; H, 5.03. Found: C,
74.71; H, 5.12.
tr a n s-3-Hyd r oxy-4′-m eth ylfla va n on e (tr a n s-2b): Yields:
43% (method A, stirring period: 5 min), 67% (method B,
stirring period: 5 h); mp 174-176 °C (EtOH), colorless
crystals. IR 3464, 3022, 2918, 2856, 1700, 1608, 1576, 1462,
er yth r o-4a :36 1H NMR δ 7.63 (dd, J ) 7.2, 1.0 Hz, 1H), 7.57
(ddd, 1H), 7.49 (m, 2H), 7.25-7.45 (m, 3H), 7.13 (d, J ) 8.3
Hz, 1H), 7.02 (ddd, 1H), 4.99 (d, J ) 6.4 Hz, 1H), 4.73 (d, J )
6.4 Hz, 1H), 3.68 (s, 1H, D2O exchangeable). 13C NMR δ 200.7,
173.0, 138.3, 138.1, 128.5, 128.2, 127.0, 124.3, 122.2, 121.0,
113.3, 86.3, 73.6.
1384, 1272, 1228, 1214, 1184, 1142, 1104, 1008, 812, 760 cm-1
.
1H NMR δ 7.93 (dd, J ) 8.0, 2.3 Hz, 1H), 7.57 (ddd, 1H), 7.49
(d, J ) 8.3 Hz, 2H), 7.29 (d, J ) 8.3 Hz, 2H), 7.01-7.17 (m,
2H), 5.11 (d, J ) 12.5 Hz, 1H), 4.66 (dd, J ) 12.5, 1.9 Hz, 1H),
3.62 (d, J ) 1.9 Hz, 1H, D2O exchangeable), 2.40 (s, 3H). Anal.
Calcd for C16H14O3 (254.29): C, 75.57; H, 5.55. Found: C,
75.85; H, 5.67.
th r eo-4a :36 1H NMR δ 7.63 (dd, J ) 7.3, 1.0 Hz, 1H), 7.58
(ddd, 1H), 7.49 (m, 2H), 7.38 (m, 2H), 7.31 (m, 1H), 7.13 (d, J
) 8.3 Hz, 1H), 7.04 (ddd, 1H), 5.32 (d, J ) 2.7 Hz, 1H), 4.75
(d, J ) 2.7 Hz, 1H), 2.84 (s, 1H, D2O exchangeable). 13C NMR
δ 200.1, 173.4, 139.5, 138.1, 128.5, 128.2, 126.4, 124.2, 122.0,
121.5, 113.4, 87.4, 73.1.
tr a n s-3-Hydr oxy-4′-m eth oxyflavan on e (tr a n s-2c): Yields:
51% (method A, stirring period: 3 min), 57% (method B,
stirring period: 8 h); mp 166-170 °C (lit.40 mp 168 °C),
colorless needles. 1H NMR δ 7.94 (dd, J ) 7.8, 1.6 Hz, 1H),
7.57 (ddd, 1H), 7.56 (d, J ) 8.7 Hz, 2H), 6.98-7.15 (m, 2H),
7.05 (d, J ) 8.7 Hz, 2H), 5.11 (d, J ) 12.4 Hz, 1H), 4.65 (d, J
) 12.4 Hz, 1H), 3.83 (s, 3H), 3.64 (s, 1H, D2O exchangeable).
tr a n s-4′-F lu or o-3-h yd r oxyfla va n on e (tr a n s-2d ): Yield:
47% (method A, stirring period: 2 min); mp 167-170 °C
(EtOH), colorless needles. IR 3464, 3076, 2900, 2832, 1698,
1606, 1576, 1512, 1472, 1462, 1296, 1274, 1228, 1212, 1158,
For the identification of the minor products cis-3a ,37 5a ,38
6,39 and 7,39 1H NMR spectra were compared with those of the
literature.
When 2′-hydroxychalcone epoxide (2a ) (114 mg, 0.51 mmol)
was treated with a mixture of ethanol (5 mL) and 0.12 M
hydrochloric acid solution (5 mL, ca. 0.59 mmol) at rt (ca. 20
°C) for 3 h and worked up as given for method B (vide infra),
86.0 mg (71%) of trans-3a was obtained, as colorless crystals,
mp 188-191 °C.
Tr ea t m en t of tr a n s-3-H yd r oxyfla va n on e (tr a n s-3a )
w it h 1,8-Dia za b icyclo[5.4.0]u n d ec-7-en e (DBU). When
trans-3a (120 mg, 0.50 mmol) was treated with DBU under
the conditions of entry 5 (Table 1) and worked up according
to the procedure given for the cyclization of 2a (vide supra), a
product ratio trans-3a :cis-3a :5a ) 89:7:4 was established by
1H NMR analysis.
1136, 1106, 1010, 832, 768 cm-1 1H NMR δ 7.94 (dd, J ) 8.1,
.
1.8 Hz, 1H), 7.51-7.62 (m, 3H), 7.02-7.28 (m, 4H), 5.13 (d, J
) 12.5 Hz, 1H), 4.60 (dd, J ) 12.5, 1.8 Hz, 1H), 3.69 (d, J )
1.8 Hz, 1H, D2O exchangeable). Anal. Calcd for C15H11FO3
(258.25): C, 69.76; H, 4.29. Found: C, 69.49; H, 4.00.
tr a n s-4′-Br om o-3-h yd r oxyfla va n on e (tr a n s-2e): Yield:
72% (method B, stirring period: 122 h); mp 173-175 °C
(EtOH), colorless needles. IR 3460, 1705, 1695, 1608, 1472,
1462, 1293, 1283, 1228, 1213, 1143, 1108, 1075, 1009, 819, 769
cm-1 1H NMR δ 7.93 (dd, J ) 7.9, 1.7 Hz, 1H), 7.60 (d, J )
.
Gen er a l P r oced u r es for th e P r ep a r a tion of 3-Hy-
d r oxyfla va n on es tr a n s-3a -i. Meth od A. To a cooled (0-5
°C) solution of 2′-hydroxychalcone (1) (2.00 mmol) in CH2Cl2
(10 mL) was added DMD as acetone solution (20 mL, 0.08-
0.10 M). After 12 h the next batch of DMD solution was added.
Additions were repeated until total consumption of the starting
chalcone was detected by TLC (hexane-acetone ) 4:1, v/v).
The solvent was removed in vacuo (bath temperature ) 25
°C), and the residue was dissolved in CH2Cl2 (15 mL). The
solution was stirred under nitrogen at room temperature and
0.4 mL of 1.5 M aqueous tetrabutylammonium hydroxide
(TBAH) (0.60 mmol) was added. After a structure-dependent
stirring period, the reaction mixture was poured into 4%
hydrochloric acid solution (25 mL) and separated and the
aqueous layer was extracted with CH2Cl2 (3 × 10 mL). The
combined organic phases were washed with water (3 × 15 mL),
dried, and concentrated. The residue was treated with cold
hexane-absolute EtOH or hexane-acetone mixture (10-20:1,
v/v), the solid crystalline residue was collected by filtration to
8.5 Hz, 2H), 7.58 (ddd, 1H), 7.47 (d, J ) 8.5 Hz, 2H), 7.13 (ddd,
1H), 7.06 (d, J ) 8.4 Hz, 1H), 5.11 (d, J ) 12.3 Hz, 1H), 4.56
(d, J ) 12.3 Hz, 1H), 3.68 (s, 1H, D2O exchangeable). Anal.
Calcd for C15H11BrO3 (319.17): C, 56.45; H, 3.47; Br, 25.04.
Found: C, 56.78; H, 3.51; Br, 25.30.
tr a n s-4′-Cya n o-3-h yd r oxyfla va n on e (tr a n s-2f): Yield:
41% (method B, stirring period: 5 h at reflux temperature),
isolated by column chromatography (toluene-ethyl acetate )
6:1, v/v); mp 161-162.5 °C (EtOH), pale yellow crystals. IR
3474, 2222, 1692, 1604, 1576, 1464, 1276, 1222, 1194, 1138,
1106, 1020, 826, 770 cm-1 1H NMR δ 7.95 (dd, J ) 7.8, 1.6
.
Hz, 1H), 7.75 (A2B2, 4H), 7.61 (ddd, 1H), 7.16 (ddd, 1H) 7.08
(d, J ) 8.4, 1.1 Hz, 1H), 5.20 (d, J ) 12.2 Hz, 1H), 4.51 (d, J
) 12.2 Hz, 1H), 3.75 (s, 1H, D2O exchangeable). Anal. Calcd
for C16H11NO3 (265.27): C, 72.45; H, 4.18; N, 5.28. Found:
C, 72.15; H, 4.08; N, 4.92.
tr a n s-6-Ch lor o-3-h yd r oxyfla va n on e (tr a n s-2g): Yields:
53% (method A, stirring period: 10 min), 72% (method B,
stirring period: 22 h); mp 130-132 °C. (EtOH), colorless
needles. IR 3468, 3462, 3076, 2892, 2844, 1698, 1600, 1470,
1456, 1424, 1286, 1260, 1224, 1196, 1142, 1122, 1086, 1016,
1
give pure trans-2 (>95% by H NMR).
Meth od B. 2′-Hydroxychalcone (1) (2.00 mmol) was epoxi-
dized by using DMD, and the reaction mixture was worked
up as given for method A. The crude epoxide was dissolved
in ethanol (20 mL), and 0.12 M hydrochloric acid solution (20
mL, ca. 2.34 mmol) was added and stirred until the completion
of the cyclization. The reaction mixture was poured into water
(100 mL) and extracted with CH2Cl2 (3 × 10 mL). The
combined organic phases were washed with water (3 × 15 mL),
980, 878, 838, 766, 708 cm-1 1H NMR δ 7.89 (d, J ) 2.6 Hz,
.
1H), 7.41-7.61 (m, 6H), 7.02 (d, J ) 8.8 Hz, 1H), 5.14 (d, J )
12.4 Hz, 1H), 4.63 (d, J ) 12.4 Hz, 1H), 3.56 (br s, 1H, D2O
exchangeable). Anal. Calcd for C15H11ClO3 (174.71): C, 65.59;
H, 4.04; Cl, 12.91. Found: C, 65.48; H, 3.86; Cl, 13.22.
tr a n s-3-Hyd r oxy-7-m eth ylfla va n on e (tr a n s-2h ): Yields:
40% (method A, stirring period: 5 min), 57% (method B,
stirring period: 5.5 h); mp 198-201 °C (EtOH), colorless
crystals. IR 3468, 2906, 1686, 1614, 1570, 1458, 1420, 1280,
(36) 1H and 13C NMR spectra were recorded at 400 and 100 MHz,
respectively.
1236, 1154, 1116, 1024, 994, 770, 700 cm-1 1H NMR δ 7.82
.
(d, J ) 8.0 Hz, 1H), 7.59 (m, 2H), 7.48 (m, 3H), 6.94 (dd, J )
8.3, 1.7 Hz, 1H), 6.86 (d, J ) 1.7 Hz, 1H), 5.12 (d, J ) 12.3 Hz,
(37) Moriarty, R. M.; Om Prakash J . Org. Chem. 1985, 50, 151.
(38) Markham, K. R.; Mabry, T. J . In The Flavonoids; Harborne, J .
B., Mabry, T. J ., Mabry, J ., Eds.; Chapman & Hall: London, 1975; pp
45-77.
(39) Atlas of Spectral Data and Physical Constants for Organic
Compounds; Grasseli, J . G., Ritchey, W. M., Eds., CRC: Cleveland;
1975.
(40) Bokadia, M. M.; Brown, B. R.; Cummings, W. J . Chem. Soc.
1960, 3308.

5382 J . Org. Chem., Vol. 61, No. 16, 1996
Patonay et al.
1H), 4.60 (d, J ) 12.3 Hz, 1H), 3.68 (br s, 1H, D2O exchange-
able), 2.39 (s, 3H). Anal. Calcd for C16H14O3 (254.29): C,
75.57; H, 5.55. Found: C, 75.33; H, 5.61.
toluene) to yield 0.40 g (6.5%) enone 8c as a yellow oil and
2,2-dimethylchromanone (2.7 g, 44%) as main product.
8c: IR (neat) 2976, 2913, 1641, 1583, 1466, 1444, 1363,
t r a n s-3′,4′-(E t h y le n e d io x y)-3-h yd r o xy -7-m e t h oxy -
m eth oxyfla va n on e (tr a n s-2i): Yields: 44% (method A,
stirring period: 3 min), 36% (method B, stirring period: 21
h); mp: 153-155 °C (EtOH), colorless crystals. IR 3448, 2928,
2880, 1682, 1610, 1658, 1512, 1446, 1434, 1296, 1254, 1208,
1293, 1242, 1222, 1158, 1014, 796, 756 cm-1
.
1H NMR δ 12.82
(s, 1H, D2O exchangeable), 7.87 (dd, J ) 8.0, 1.7 Hz, 1H), 7.34
(ddd, 1H), 6.97 (dd, J ) 8.4, 1.2 Hz, 1H), 6.87 (ddd, 1H), 6.79
(m, 1H), 2.21 (d, J ) 1.3 Hz, 1H), 2.04 (d, J ) 1.3 Hz, 1H). 13
C
NMR δ 196.6, 163.5, 158.0, 135.9, 135.8, 130.0, 120.7, 120.1,
118.7, 118.5, 28.0. 21.2. MS 176 (M+•, 4), 161 (100), 131 (3).
121 (31), 120 (6), 89 (9), 83 (14), 65 (20).
1154, 1114, 1094, 1064, 1034, 1012, 856, 800 cm-1 1H NMR
.
δ 7.86 (d, J ) 8.4 Hz, 1H), 7.10 (d, J ) 1.4 Hz, 1H), 7.05 (dd,
J ) 8.1, 1.4 Hz, 1H), 6.94 (d, J ) 8.1 Hz), 6.76 (dd, J ) 8.4,
1.5 Hz, 1H), 6.68 (d, J ) 1.5 Hz, 1H), 5.20 (s, 2H), 5.01 (d, J
) 12.1 Hz, 1H), 4.55 (d, J ) 12.1 Hz, 1H), 4.29 (s, 4H), 3.70 (s,
1H, D2O exchangeable), 3.70 (s, 3H). Anal. Calcd for C19H18O7
(358.35): C, 63.68; H, 5.06. Found: C, 63.82; H, 5.03.
1-[2-Hyd r oxy-4-(tosyloxy)p h en yl]-3-m eth yl-2-bu ten -1-
on e (8f). A mixture of 1-(2,4-dihydroxyphenyl)-3-methyl-2-
propen-1-one (8e)27 (956 mg, 5.00 mmol), p-toluenesulfonyl
chloride (1.35 g, 7.08 mmol), powdered anh K2CO3 (800 mg,
5.79 mmol), and absolute acetone (50 mL) was stirred at room
temperature for 18 h, poured into water (500 mL), extracted
with CH2Cl2 (3 × 150 mL), and dried. After concentration
under reduced pressure the obtained residue was submitted
to silica gel chromatography (eluent: hexane-acetone ) 2:1,
v/v) to give 391 mg (23%) of tosylate 8f as pale yellow crystals,
mp 109-111 °C (hexane-absolute EtOH). IR 3060, 3040,
2932, 1640, 1578, 1504, 1494, 1446, 1366, 1308, 1294, 1228,
tr a n s-3,7,3′,4′-Tet r a h yd r oxyfla va n on e or (()-F u st in
(tr a n s-2j). A sample of 545 mg (2.00 mmol) of 2′,4′,3,4-
tetrahydroxychalcone (1j) was treated with DMD (20 mL) in
acetone solution. Fresh batches of dioxirane were added
repeatedly until complete consumption of the starting chal-
cone, and the reaction mixture was concentrated (bath tem-
perature ) 25 °C) and submitted to silica gel chromatography
(toluene-absolute methanol ) 5:1, v/v) to give 291 mg (50%)
of dihydroflavonol 2j; mp 210-220 °C dec (lit.41 mp 211 °C),
brownish powder. IR 3412 br, 3260 br, 1676, 1610, 1522, 1464,
1
1192, 1176, 1122, 1092, 976, 868, 850, 834, 812, 728 cm-1. H
NMR (Me2CO-d6) δ 13.00 (s, 1H, D2O exchangeable), 8.02 (dd,
J ) 9.3, 1.0 Hz, 1H), 7.80 (d, J ) 8.0 Hz, 2H), 7.50 (d, J ) 8.0
Hz, 2H), 6.99 (m, 1H), 6.63 (dd, J ) 9.3, 2.4 Hz, 1H), 6.61 (d,
J ) 1.0 Hz, 1H), 2.47 (s, 3H), 2.22 (d, J ) 2.3 Hz, 3H), 2.06 (d,
3H, overlaps with the solvent signal). Anal. Calcd for
C18H18O5S (346.41): C, 62.41; H, 5.24; S, 9.26. Found: C,
62.19; H, 5.27; S, 9.38.
Gen er a l P r oced u r e for th e Oxid a tion of 1-(2-Hyd r oxy-
p h en yl)-2-p r op en -1-on es 8 by Dim eth yld ioxir a n e. To a
solution of enone 8 (2.00-2.50 mmol) in CH2Cl2 (10 mL) was
added DMD (20 mL) as acetone solution (0.08-0.10 M) and
allowed to stand at 0-5 °C. Addition of DMD was repeated
in 12 h intervals, and the reaction was monitored by TLC
(hexane-acetone ) 4:1, v/v). The solvent was removed in
vacuo (bath temperature ) 25 °C), and the residue was
submitted to silica gel chromatography. Further experimental
details are given in Table 3.
3-Hyd r oxych r om a n on e (10a ) a n d 2-(h yd r oxym eth yl)-
3-cou m a r a n on e (11a ), cf. Ta ble 3, en tr y 2, were obtained
from 8a (370 mg, 2.50 mmol) according to the above general
procedure with 8:1 (v/v) toluene-ethyl acetate mixture as
eluent.
10a : Yield: 5.1%; mp 56-57.5 °C (lit.24 mp 57-58 °C); Rf
) 0.24. 1H NMR δ 7.88 (dd, J ) 7.8, 1.7 Hz, 1H), 7.53 (ddd,
1H), 7.07 (t, 1H), 6.91 (d, J ) 8.3 Hz), 5.65 (ABX m, 2H), 4.15
(ABX dd, 1H), 3.65 (s, 1H, D2O exchangeable).
1322, 1266 br, 1160, 1108, 1016, 992, 806 cm-1
.
1H NMR
(DMSO-d6) δ 10.60 (s, 1H, D2O exchangeable), 9.00, 8.96 (2 ×
s, 2H, D2O exchangeable), 7.92 (d, J ) 8.7 Hz, 1H), 6.89 (m,
1H), 6.75 (m, 2H), 6.53 (dd, J ) 8.7, 2,2 Hz, 1H), 6.30 (d, J )
2.2 Hz, 1H), 5.49 (d, J ) 5.5 Hz, 1H, D2O exchangeable), 4.97
(d, J ) 11.4 Hz, 1H), 4.41 (dd, J ) 11.4, 5.5 Hz, 1H).
tr a n s-3,7-Dih yd r oxy-3′,4′-(et h ylen ed ioxy)fla va n on e
(tr a n s-2k ). A mixture of 156 mg (0.435 mmol) trans-3′,4′-
(ethylenedioxy)-3-hydroxy-7-(methoxymethoxy)flavanone (trans-
2i), Amberlyst 15 (0.3 g) and methanol (10 mL) was stirred at
50 °C for 3.5 h. The resin was removed by filtration and
washed with hot methanol (3 × 10 mL), and the combined
filtrate was concentrated under reduced pressure. The residue
was crystallized from diisopropyl ether to afford 104 mg (76%)
brownish powder, mp 227-230 °C. IR 3446, 2938, 2878, 1676,
1654, 1612, 1510, 1466, 1436, 1384, 1310, 1260, 1156, 1106,
1064, 1008, 924, 890, 808 cm-1
.
1H NMR (DMSO-d6) δ 10.62
(br s, 1H, D2O exchangeable), 7.53 (d, J ) 9.1 Hz, 1H), 7.05
(d, J ) 1.4 Hz, 1H), 6.99 (dd, J ) 9.1, 1.4 Hz, 1H), 6.88 (d, J
) 9.1 Hz, 1H), 6.53 (dd, J ) 9.3, 2.4 Hz, 1H), 6.32 (d, J ) 2.4
Hz, 1H), 5.05 (d, J ) 11.6 Hz, 1H), 4.48 (d, J ) 11.6 Hz, 1H).
Anal. Calcd for C17H14O6 (314.30): C, 64.97; H, 4.49. Found:
C, 64.95; H, 4.43.
1-(2-Hyd r oxyp h en yl)-2-p r op en -1-on e (8a ). A mixture of
2′-hydroxyacetophenone (6.0 mL, 49.8 mmol), dimethylammo-
nium chloride (5.55 g, 68.0 mmol), paraformaldehyde (2.01 g),
2-propanol (10 mL), and concd hydrochloric acid (0.2 mL) was
refluxed for 1 h and was allowed to stand in the refrigerator
overnight. The colorless precipitate was collected by filtration,
washed with diethyl ether (4 × 30 mL), dissolved in water (750
mL), and steam-distilled. The distillate was extracted with
CH2Cl2 (3 × 150 mL), dried, and concentrated under reduced
pressure. Silica gel chromatography (eluent: toluene) of the
residue afforded 1.20 g (16%) of enone 8a as a yellow oil (lit.25
bp 67-68 °C/1-2 Torr). IR (neat) 3046 br, 1644, 1634, 1614,
1592, 1486, 1446, 1410, 1358, 1288, 1240, 1208, 1158, 1000,
11a : Yield: 53%; mp 95-98 °C (hexane-ethyl acetate); Rf
) 0.10. IR 3424, 2922, 1712, 1616, 1478, 1326, 1310, 1196,
1146, 1092, 1022, 758 cm-1
.
1H NMR δ 7.59-7.68 (m, 2H),
7.06-7.19 (m, 2H), 4.68 (ABX dd, 1H), 4.10 (ABX m, 2H), 2.24
(s, 1H, D2O exchangeable). 13C NMR δ 184.2, 173.0, 138.1,
123.9, 121.8, 121.0, 113.3, 85.9, 61.5. Anal. Calcd for C9H8O3
(164.16): C, 65.85; H, 4.91. Found: C, 65.67; H, 4.79.
cis,t r a n s-3-H yd r oxy-7-m e t h oxy-2-m e t h ylch r om a n -
on e (10b) a n d er yth r o,th r eo-2-(1-h yd r oxyeth yl)-6-m eth -
oxy-3-cou m a r a n on e (11b), cf. Ta ble 3, en tr y 3, were
obtained from 8b26 (384 mg, 2.00 mmol) according to the above
general procedure with 4:1 (v/v) hexane-acetone mixture as
eluent.
976, 832, 752, 716 cm-1
.
1H NMR δ 12.53 (s, 1H, D2O
exchangeable), 7.80 (dd, J ) 8.0, 1.5 Hz, 1H), 7.55 (ddd, 1H),
7.50 (dd, J ) 16.9, 10.5 Hz, 1H), 6.87-7.03 (m, 2H), 6.56 (dd,
J ) 16.9, 1.6 Hz, 1H), 5.96 (dd, J ) 10.5, 1.6 Hz, 1H). Anal.
Calcd for C9H8O2 (148.16): C, 72.96; H, 5.44. Found: C, 73.11;
H, 5.19.
cis,tr a n s-10b: Yield: 4.9%; colorless crytals; mp 126-148
°C (lit.17a mp 152 °C for trans-10b diastereomer, but stereo-
chemistry based only on chemical properties); Rf ) 0.24. IR
3410, 2986, 2942, 2844, 1668, 1616, 1574, 1446, 1384, 1252,
1198, 1164, 1102, 1070, 996, 980, 840 cm-1 1H NMR: trans-
.
1-(2-Hydr oxyph en yl)-3-m eth yl-2-bu ten -1-on e (8c). Phen-
yl 3-methyl-2-butenoate (6.20 g, 35.18 mmol) was treated with
AlCl3 (6.51 g, 48.82 mmol) according to the literature proce-
dure.29 After workup and removal of the diethyl ether the
residue was submitted to column chromatography (eluent:
10b δ 4.12 (d, J ) 11.8 Hz, 1H), 3.84 (s, 3H), 1.64 (d, J ) 6.1
Hz, 3H); cis-10b δ 3.91 (d, J ) 3.7 Hz, 1H), 3.81 (s, 3H), 1.51
(d, J ) 5.2 Hz, 3H). Unassigned signals: δ 7.81 (d, J ) 8.8
Hz, 1H), 6.63 (dd, J ) 8.8, 2.4 Hz, 1H), 6.44 (d, J ) 2.4 Hz,
1H), 4.22 (m, 1H). The diastereomeric ratio trans-10b:cis-10b
) 85:15 was determined by 1H NMR analysis of the 7-MeO
and 2-Me signals. Anal. Calcd for C11H12O4 (208.22): C, 63.45;
H, 5.81. Found: C, 63.27; H, 5.90.
(41) Fourie, T. G.; Ferreira, D.; Roux, D. G. J . Chem. Soc., Perkin
Trans. 1 1977, 125.

1-(2-Hydroxyphenyl)-2-propen-1-one Epoxides
J . Org. Chem., Vol. 61, No. 16, 1996 5383
er yth r o,th r eo-11b: Yield: 37%; yellowish oil; Rf ) 0.12. IR
155.9, 146.1, 132.4, 130.2, 128.6, 128.4, 117.5, 115.5, 112.4,
84.5, 77.0, 26.9, 21.9, 17.5. Anal. Calcd for C18H18O6S
(362.40): C, 59.66; H, 5.01; S, 8.85. Found: C, 59.81; H, 4.83;
S, 8.80.
(neat) 3440 br, 2976, 2936, 2844, 1710, 1694, 1614, 1504, 1454,
1446, 1340, 1258 br, 1150, 1102, 1016, 984, 946, 830 cm-1 13C
.
NMR δ 198.5, 198.0, 175.6, 168.5, 168.4, 125.3, 125.1, 114.8,
114.28, 111.9, 111.7, 96.1, 96.0, 88.6, 87.9, 67.8, 67.3, 55.8, 18.9,
18.0. 1H NMR: erythro-11b δ 7.54 (d, J ) 8.6 Hz, 1H), 6.64
(dd, J ) 8.6, 1.7 Hz, 1H), 6.57 (br s, 1H), 4.48 (overlapping
doublet, 1H), 4.13 (m, 1H), 3.88 (s, 3H), 3.26 (br s, 1H, D2O
exchangeable), 1.32 (d, J ) 6.3 Hz, 3H); threo-11b δ 7.52 (d, J
) 8.5 Hz, 1H), 6.63 (dd, J ) 8.5, 1.7 Hz, 1H), 6.57 (br s, 1H),
4.48 (overlapping doublet, 1H), 4.30 (m, 1H), 3.87 (s, 3H), 2.60
(br s, 1H, D2O exchangeable), 1.41 (d, J ) 6.5 Hz, 3H). erythro-
11b: threo-11b ) 3:2. The diastereomeric ratio was deter-
mined by 1H NMR analysis of the 6-MeO and 2′-H signals.
Anal. Calcd for C11H12O4 (208.22): C, 63.45; H, 5.81. Found:
C, 63.49; H, 5.54.
11e: Yield: 17%; yellowish oil; Rf ) 0.13. IR 3430, 2971,
2927, 1709, 1603, 1449, 1371, 1233, 1210, 1188, 1150, 990, 795
cm-1 1H NMR δ 7.76 (d, J ) 8.4 Hz, 2H), 7.57 (d, J ) 9.4 Hz,
.
1H), 7.36 (d, J ) 8.4 Hz, 2H), 6.91 (d, J ) 2.0 Hz, 1H), 6.70
(dd, J ) 9.4, 2.0 Hz, 1H), 4.41 (s, 1H), 3.60 (br s, 1H, D2O
exchangeable), 2.47 (s, 3H), 1.34, 1.25 (2 × s, 6H). Anal. Calcd
for C18H18O6S (362.40): C, 59.66; H, 5.01; S, 8.85. Found: C,
59.55; H, 5.19; S, 8.73.
Oxid a tion of 1-(2-Hyd r oxy-4-m eth oxyp h en yl)-3-m eth -
yl-2-p r op en -1-on e (8d ) by Alk a lin e Hyd r ogen P er oxid e,
cf. Ta ble 3, En tr y 6. A solution of enone 8d (465 mg, 2.25
mmol), 21% H2O2 (1.0 mL, ca. 6.18 mmol), and 2 N NaOH (1.0
mL, 4.0 mmol) in methanol (20 mL) was stirred at rt (ca. 20
°C) for 8 h. The reaction mixture was neutralized with acetic
acid, diluted with water (300 mL), extracted with CH2Cl2 (3
× 50 mL), dried and concentrated. Silica gel chromatography
(eluent: hexane-acetone ) 4:1, v/v) of the residue afforded
238 mg (48%) of 2,2-dimethyl-3-hydroxy-7-methoxychro-
manone (10d ) and 36.0 mg (7.2%) of 2-(1-hydroxy-1-methyl-
ethyl)-6-methoxy-3-coumaranone (11d ), mp 71-75 °C (hex-
ane), colorless crystals.
2,2-Dim eth yl-3-h yd r oxych r om a n on e (10c) a n d 2-(1-
h yd r oxy-1-m eth yleth yl)-3-cou m a r a n on e (11c), cf. Ta ble
3, en tr y 4, were obtained from 8c (360 mg, 2.04 mmol)
according to the above general procedure with 4:1 (v/v)
hexane-acetone mixture as eluent.
10c: Yield: 47%; mp 49-51 °C (hexane); colorless crystals.
IR 3484, 2974, 2934, 2834, 1702, 1606, 1474, 1460, 1320, 1290,
1252, 1232, 1144, 1120, 1100, 1012, 924, 772, 764 cm-1
.
1H
NMR δ 7.81 (dd, J ) 7.8, 1.6 Hz, 1H), 7.50 (ddd, 1H), 6.92-
7.05 (m, 2H), 4.44 (s, 1H), 4.08 (br s, 1H, D2O exchangeable),
1.65, 1.22 (2 × s, 6H). 13C NMR δ 190.4, 159.7, 136.8, 126.6,
121.0, 118.7, 118.4, 83.4, 77.0, 26.8, 17.2. Anal. Calcd for
C11H12O3 (192.22): C, 68.73; H, 6.34. Found: C, 68.55; H, 6.39.
11c: Yield: 31%; yellowish oil. IR (neat) 3478, 2976, 2934,
1712, 1692, 1620, 1614, 1474, 1462, 1378, 1324, 1310, 1212,
1194, 1176, 1144, 1020, 984, 856, 756. 1H NMR δ 7.65 (d, J )
7.0 Hz, 1H), 7.63 (ddd, 1H), 7.05-7.17 (m, 2H), 4.37 (s, 1H),
2.88 (br s, 1H, D2O exchangeable), 1.35, 1.23 (2 × s, 6H). 13C
NMR δ 210.2, 172.8, 138.3, 124.2, 122.1, 121.7, 113.3, 89.1,
72.4, 25.6, 24.2. Anal. Calcd for C11H12O3 (192.22): C, 68.73;
H, 6.34. Found: C, 68.53; H, 6.21.
11d : IR 3462, 2980, 1692, 1614, 1500, 1446, 1370, 1272,
1246, 1188, 1150, 1108, 1016, 932, 828 cm-1 1H NMR δ 7.56
.
(d, J ) 8.6 Hz, 1H), 6.66 (dd, J ) 8.6, 2.0 Hz, 1H), 6.58 (d, J
) 2.0 Hz, 1H), 4.39 (s, 1H), 3.89 (s, 3H), 3.34 (s, 1H, D2O
exchangeable), 1.37, 1.25 (2 × s, 6H). Anal. Calcd for C12H14O4
(222.24): C, 64.85; H, 6.35. Found: C, 64.63; H, 6.41.
Oxid a tion of 1-(2-Hyd r oxy-4-m eth oxyp h en yl)-3-m eth -
yl-2-p r op en -1-on e (8d ) b y m -Ch lor op er b en zoic Acid
(m CP BA) cf. Ta ble 3, En tr y 7. A solution of enone 8d (465
mg, 2.25 mmol) and mCPBA (432 mg, 2.50 mmol) in CH2Cl2
(20 mL) was allowed to stand at 0 °C for 6 d, and a new portion
of mCPBA (432 mg, 2.50 mmol) was added, which was
repeated after 2 d. After 19 d, the precipitate was removed
by filtration and washed with CH2Cl2 (2 × 10 mL) and the
solvent evaporated under reduced pressure. The residue was
submitted to silica gel chromatography (eluent: toluene-ethyl
acetate ) 8:1, v/v) to give 55.0 mg of unreacted 8d , 146 mg
(33%) of 2,2-dimethyl-3-hydroxy-7-methoxychromanone (10d ),
43.0 mg (9.8%) of 1-(2,5-dihydroxy-4-methoxyphenyl)-3-methyl-
2-buten-1-one (12d ), and 120 mg (27%) of 2-(1-hydroxy-1-
methylethyl)-6-methoxy-3-coumaranone (11d ).
2,2-Dim eth yl-3-h yd r oxy-7-m eth oxych r om a n on e (10d )
an d 1-(2,5-dih ydr oxy-4-m eth oxyph en yl)-3-m eth yl-2-bu ten -
1-on e (12d ), cf. Ta ble 3, en tr y 5, were obtained from 8d 28
(465 mg, 2.25 mmol) according to the above general procedure
with 4:1 (v/v) hexane-acetone mixture as eluent.
10d : Yield: 26%; mp 112-113.5 °C (hexane) (lit.17a mp 110
°C); colorless crystals. IR 3472, 1672, 1614, 1576, 1444, 1268,
1246, 1204, 1098, 1028, 1010, 820, 798 cm-1 1H NMR δ 7.74
.
(d, J ) 8.8 Hz, 1H), 6.57 (dd, J ) 8.8, 2.2 Hz, 1H), 6.38 (d, J
) 2.2 Hz, 1H), 4.36 (s, 1H), 3.84 (s, 4H), 1.63, 1.22 (2 × s, 6H).
13C NMR δ 192.5, 166.9, 161.9, 128.35, 112.4, 109.8, 101.4,
83.6, 76.6, 55.6, 26.9, 17.4.
Ack n ow led gm en t. This work was supported by the
joint European Community (COST Project D2/0005/94).
Additionally, the work in Debrecen was financially
supported by the National Fund of Science and Research
(OTKA Grant No: T7459), the National Committee for
Technological Development (OMFB Grant No: 107), and
Alkaloida Chemical Co., Ltd. and the work in Wu¨rzburg
by the Deutsche Forschungsgemeinschaft (Schwerpunk-
programm “Peroxidchemie: Mechanistische und Pra¨-
pative Aspekts der Sauerstofftransfers”). The valuable
technical assistance by Mrs. E. M. Rima´n is highly
appreciated.
12d : Yield: 7.3%; mp 116-120 °C (hexane-ethyl acetate);
orange leaflets. IR 3364, 1632, 1576, 1512, 1498, 1450, 1398,
1254, 1208, 1180, 1156, 992, 878, 798 cm-1 1H NMR δ 13.09
.
(s, 1H, D2O exchangeable), 7.26 (s, 1H), 6.63 (t, J ) 1.3 Hz,
1H), 6.45 (s, 1H), 5.23 (s, 1H, D2O exchangeable), 3.92 (s, 3H),
2.18 (d, J ) 1.3 Hz, 3H), 2.01 (d, J ) 1.3 Hz, 3H). 13C NMR
δ 189.9, 159.7, 156.2, 153.2, 137.7, 120.3, 113.5, 113.4, 99.9,
56.1, 28.0, 21.1. Anal. Calcd for C12H14O4 (222.24): C, 64.85;
H, 6.35. Found: C, 65.08; H, 6.29.
2,2-Dim eth yl-3-h yd r oxy-7-(tosyloxy)ch r om a n on e (10e)
a n d 2-(1-h yd r oxy-1-m eth yleth yl)-6-(tosyloxy)-3-cou m a -
r a n on e (11e), cf. Ta ble 3, en tr y 8, were obtained from 8e
(270 mg, 0.78 mmol) according to the above general procedure
with 3:1 (v/v) hexane-acetone mixture as eluent.
Su p p or tin g In for m a tion Ava ila ble: Table with charac-
teristic coupling constants of erythro- and threo-4a (1 page).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any masthead
page for ordering information.
10e: Yield: 68%; mp 122-124.5 (hexane-ethyl acetate),
colorless crystals; Rf ) 0.18. IR 3356, 2972, 1692, 1610, 1440,
1378, 1254, 1442, 1192, 1172, 1088, 984, 866, 818, 810, 794,
728, 714 cm-1
.
1H NMR δ 7.75 (overlapping doublets, 3H),
7.34 (d, J ) 7.8 Hz, 2H), 6.70 (d, J ) 1.9 Hz, 1H), 6.62 (dd, J
) 7.5, 1.9 Hz, 1H), 4.39 (s, 1H), 3.72 (s, 1H, D2O exchangeable),
2.46 (s, 3H), 1.63, 1.19 (2 × s, 6H). 13C NMR δ 193.4, 160.9,
J O960163Z