Kinetics of the reactions of flavylium ions with π-nucleophiles

Article abstract of DOI:10.1002/1099-0690(200112)2001:23<4451::aid-ejoc4451>3.0.co;2-f

The kinetics of the reactions of the flavylium ion 1a and the 4′-methoxyflavylium ion 1b with various π-nucleophiles and tributylstannane were investigated photometrically in dichloromethane. Electrophilicity parameters E(1a) = -3.46 and E(1b) = -4.96 were derived from the equation log k (20°C) = s(E + N); these allow the prediction of potential reaction partners of the flavylium ions 1a and 1b.

Full text of DOI:10.1002/1099-0690(200112)2001:23<4451::aid-ejoc4451>3.0.co;2-f

FULL PAPER
Kinetics of the Reactions of Flavylium Ions with π-Nucleophiles
Claudia Fichtner,[a] Grigoriy Remennikov,[a] and Herbert Mayr*[a]
Dedicated to Prof. Dieter Hoppe on the occasion of his 60th birthday
Keywords: Kinetics / Linear free-energy relationships / Carbocations / Electrophilic additions / Nucleophilic additions
The kinetics of the reactions of the flavylium ion 1a and the
4Ј-methoxyflavylium ion 1b with various π-nucleophiles and
E(1b) = −4.96 were derived from the equation log k (20 °C) =
s(E + N); these allow the prediction of potential reaction part-
tributylstannane were investigated photometrically in dichlo- ners of the flavylium ions 1a and 1b.
romethane. Electrophilicity parameters E(1a) = −3.46 and
Introduction
carbocations and related species and allow predictions of
the rates of reaction with potential nucleophilic reaction
partners.[7]
Flavylium ions 1 (ϭ 2-aryl-1-benzopyrylium ions), di-
versely substituted at the 3,3Ј,4Ј,5,5Ј and 7-positions by
OH, OMe, or glycosyloxy groups, form the nucleus of the
anthocyanin pigments responsible for a large number of
plant colors.[1]
log k (20 °C) ϭ s (E ϩ N)
(1)
where E ϭ electrophilicity parameter, N ϭ nucleophilicity
parameter and s ϭ nucleophile-dependent slope parameter
It was the goal of this work to determine the reactivity
parameter E of some flavylium ions and to use these para-
meters for defining the scope of potential nucleophilic reac-
tion partners. For this purpose, we have studied the kinetics
of the reactions of the parent and the 4Ј-methoxy-substi-
tuted flavylium ion with π-nucleophiles.
Some of them have been used as food colorants[2] and,
more recently, as laser dyes[3] and sensibilizers for electro-
photographic recordings.[4] Presently, their use as a basis for
optical memory systems is being investigated.[5]
As ambident electrophiles, flavylium ions may react with
nucleophiles at the 2- or 4-position to yield 2-aryl-2H- or
2-aryl-4H-1-benzopyrans, respectively. Like other 2-substi-
tuted 1-benzopyrylium ions, they generally prefer reaction
at the 4-position.[1] Detailed kinetic investigations of the hy-
dration of the parent and of 4Ј-substituted flavylium ions
indicated that even hard nucleophiles such as H2O or ϪOH
attack the 4-position somewhat faster than the 2-position.[6]
The latter reactions may be reversible, and the pH-depen-
dent equilibrium mixture consists of the 2-aryl-2H- and 2-
aryl-4H-1-benzopyrans and chalcones (or their anions),
arising from ring-opening of the 2-hydroxy-2-phenyl-2H-1-
benzopyran.[6]
Results
Synthesis of the Flavylium Salts
By modifying the procedure reported for the preparation
of 1a-ClO4,[8] the tetrafluoroborate and triflate salts of the
flavylium ions 1a and 1b were synthesized by refluxing the
salicylideneacetophenones 2a and 2b,[9] respectively, in
either tetrafluoroboric or triflic acid (Scheme 1). An alter-
native synthetic route for 1b-BF4 has been described by Ka-
tritzky.[10]
Kinetic investigations of the reactions of flavylium ions
with C-nucleophiles have not been reported. Recently, we
have shown that the electrophilicity parameters E defined
by Equation (1), provide a general ordering principle for
[a]
Department Chemie, Ludwig-Maximilians-Universität
München,
Butenandtstr. 5-13 (Haus F), 81377 München, Germany
Fax: (internat.) ϩ49-(0)89/2180-7717
E-mail: Herbert.Mayr@cup.uni-muenchen.de
Supporting information for this article is available on the
WWW under http://www.eurjoc.com or from the author.
Scheme 1
Eur. J. Org. Chem. 2001, 4451Ϫ4456
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
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4451

C. Fichtner, G. Remennikov, H. Mayr
FULL PAPER
Reactions of Flavylium Salts with Nucleophiles
evaporating the solvent. Subsequent attempts to purify the
crude sample of 10a by chromatography (silica gel, chloro-
form) again gave a mixture of 10a and 11a.[12,13,14]
As described in Scheme 2, the flavylium ions 1a and 1b
are attacked by the nucleophiles 3Ϫ6 in the 4-position,
analogous to the reactions with other nucleophiles.[1]
Kinetics
The rate constants of the reactions of the flavylium ions
1a and 1b with the nucleophiles 3Ϫ6 were determined by
monitoring the decay of the flavylium absorbances at λ ϭ
410 Ϯ 5 nm (1a) or 470 Ϯ 5 nm (1b) using the equipment
and the data evaluation procedures described previ-
ously.[15a] The reactions followed second-order kinetics, first
order with respect to flavylium ion and first order with re-
spect to nucleophile.
For unknown reasons, the reproducibility of the second-
order rate constants was unusually low with a standard de-
viation of a factor of 1.14. Rate constants obtained with
different counterions (tetrafluoroborate or triflate) agreed
within this range, indicating that the counterions come into
play after the rate-determining step. This observation is in
agreement with the reports that rate constants independent
of the counterions were observed for reactions of benzhy-
drylium salts with allylsilanes[15b] and silylated enol
ethers.[15c] For the reaction of 1b with 4, the slowest reaction
of this series, deviations from the second-order rate law
were observed after 20Ϫ30% of conversion, probably be-
cause of decomposition of 4 by acidic impurities. Second-
order kinetics over more than 85% of conversion were ob-
tained, however, when the reaction of 1b-OTf with 4 was
performed in the presence of 2,6-di-tert-butylpyridine.
Scheme 2
Table 1. Rate constants and activation parameters for the reactions
of the flavylium ions 1a and 1b with the nucleophiles 3Ϫ6 in
CH2Cl2
The reactions of the tetrafluoroborate salts of 1a and 1b
with tributylstannane 3 yielded the flavenes 7a (65%) and
7b (70%), respectively, which were identified by comparison
Reactants k (20 °C)/L molϪ1 sϪ1 ∆H‡/kJ molϪ1 ∆S‡/J molϪ1 KϪ1
1
of their H NMR spectra with those of the products ob-
tained from 1a-BF4 and 1b-BF4 and sodium borohy-
1a ϩ 4
5.12 Ϯ 0.50
72.6 Ϯ 10.5
29.62 Ϯ 1.71 Ϫ130.16 Ϯ 6.59
25.84 Ϯ 1.37 Ϫ121.01 Ϯ 6.10
dride[11a] or lithium aluminum hydride.[11b]
5
While the reaction of 1a-BF4 with (2-methylallyl)trime-
thylsilane 4 gave 8a in 90% yield, the yield of 8b from the
corresponding reaction of the 4-methoxy analogue 1b-BF4
was only 34% even after prolonged reaction times.
6
3
(5.69 Ϯ 0.50) ϫ 102 27.01 Ϯ 0.95 Ϫ99.90 Ϯ 4.27
(2.12 Ϯ 0.17) ϫ 103 27.80 Ϯ 0.96 Ϫ86.26 Ϯ 4.01
ϪϪ
1b ϩ 4
(2.56 Ϯ 0.41) ϫ 10Ϫ1 ϪϪ
5
6
3
1.80 Ϯ 0.02
19.1 Ϯ 1.61
27.94 Ϯ 1.55 Ϫ144.60 Ϯ 6.06
31.85 Ϯ 1.04 Ϫ111.62 Ϯ 4.26
A mixture of product 9 and 4H-flavene 7a was obtained
from the reaction of 1a-BF4 and 1-(trimethylsiloxy)cy-
clohexene (5) probably due to hydride transfer from 9 to 1a.
A mixture of 10a (12%, colorless) and 11a (47%, yellow)
was isolated from the reaction of 1a-OTf with 1-phenyl-1-
(trimethylsiloxy)ethene (6). The reaction of 1b-OTf with 6
proceeded analogously (Scheme 2). When 2.3 equivalents of
6 were added to solutions of 1a-OTf or 1b-BF4 in CD2Cl2,
observation of the reaction by 1H NMR spectroscopy
showed the exclusive formation of 10a and 10b, respectively.
Therefore, compounds 11a and 11b must have been pro-
duced by oxidation during the workup process. This inter-
pretation is supported by the finding that 10a was also ob-
served as the only product in the 1H NMR spectrum of the
residue obtained by combining 1a-BF4 with 6 in dichloro-
(2.47 Ϯ 0.10) ϫ 102 33.01 Ϯ 0.75 Ϫ86.37 Ϯ 2.97
Table 2. Determination of the electrophilicity parameters E of the
flavylium ions 1a and 1b
Nucleophile
N[a]
s[a]
E(1a) E(1b)
(2-Methylallyl)trimethylsilane (4)
1-(Trimethylsiloxy)cyclohexene (5)
1-Phenyl-1-(trimethylsiloxy)ethene (6) 6.22 0.96 Ϫ3.35 Ϫ4.89
4.41 0.96 Ϫ3.67 Ϫ5.03
5.21 1.00 Ϫ3.35 Ϫ4.95
E (average) ϭ Ϫ3.46 Ϫ4.96
[a]
From ref.[16]
The rate constants given in Table 1 and the N and s para-
methane, stirring at room temperature for four hours, and meters of the π-nucleophiles 4Ϫ6[16] listed in Table 2 can be
4452
Eur. J. Org. Chem. 2001, 4451Ϫ4456

Kinetics of the Reactions of Flavylium Ions with π-Nucleophiles
FULL PAPER
substituted into Equation (1) to give the E parameters for and 1b are comparable to the tropylium ion and acceptor-
the flavylium ions 1a and 1b. The two right-hand columns substituted diazonium ions.
of Table 2 show that the E parameters derived for 1a and 1b
The electron-donating effect of the p-methoxy group re-
from reactions with different nucleophiles are very similar, duces the electrophilicity of 1b relative to 1a by 1.5 logarith-
indicating the validity of Equation (1) for describing these mic units. This effect is slightly smaller than in the more
reactions.
electrophilic carboxonium and benzhydryl cations depicted
The potential of Equation (1) to describe the electrophilic in Table 3 because of the reduced electron demand of the
reactivities of 1a and 1b is further illustrated by the finding flavylium ions.
that the rate constants calculated for the hydride abstrac-
Table 3. The effect of p-methoxy substitution on the electrophilici-
tions from tributylstannane 3 (N ϭ 9.96, s ϭ 0.55)[16] with
ties of phenyl-substituted carbenium ions
1a (kcalc ϭ 3.76 ϫ 103 L molϪ1 Ϫ1) and 1b (kcalc ϭ 5.62
s
ϫ 102 L molϪ1 Ϫ1) deviated from the experimental values
s
(Table 1) only by factors of 1.8 and 2.3, respectively. For
the attack of H2O (N ϭ 5.80, s ϭ 0.80)[7a] at C-4 one calcu-
lates first-order rate constants of 74 sϪ1 (20 °C, 1a) and
4.70 sϪ1 (20 °C, 1b), which have to be compared with
McClelland’s experimental values of 8.10 sϪ1 (25 °C, 1a)[6]
and 0.91 sϪ1 (25 °C, 1b).[6] In view of the wide range of
reactivity and structural variety covered by Equation (1),
we consider deviations of less than one order of magnitude
between calculated and experimental rate constants as quite
satisfactory. The averaged E parameters given in Table 2,
can thus be considered to be a proper representation of the
electrophilicities of 1a and 1b.
[a]
From rate constants in ref.[17b] using the procedure described in
ref.[16] [b] From ref.[16] [c] This work.
We have previously discussed that electrophiles can be
expected to react with nucleophiles if E ϩ N Ͼ Ϫ5.[7] From
this rule of thumb, one can conclude that 1a should react
with nucleophiles of N Ͼ Ϫ1.5, while 1b should only be
attacked by stronger nucleophiles with N Ͼ 0.0.
Discussion
The cationic electrophiles characterized so far cover a re-
activity range of 19 orders of magnitude, from the highly
reactive tert-butyl cation (E ϭ 9)[17a] to the well-stabilized
bis-lilolidin-8-yl-carbenium ion (E ϭ Ϫ10.04).[16] The flavy-
lium ions 1a and 1b are positioned close to the center of
the present scale, although somewhat nearer to the low elec-
trophilicity end. Some electrophiles with similar reactivities
are depicted in Figure 1, showing that the flavylium ions 1a
In previous work, flavylium ions have only been com-
bined with strong nucleophiles, for example phenylmagne-
sium bromide[18a] or lithium phenylacetylide,[18b] to give 4-
substituted 4H-flavenes. Analogous reactions with carb-
anions generated in situ from 1,3-diketones, nitromethane,
cyanoacetates or malononitriles (N ϭ 17Ϫ22[19]) have been
reported by Kröhnke.[20] It has also been described that en-
amines generated in situ (N Ͼ 11[16]) could be trapped by
the flavylium salt 1a-ClO4.[21] The weakest nucleophiles so
far investigated were N,N-dialkylanilines[22,23] (N ϭ 5.6[24]),
which gave 4-aryl-4H-flavenes with 1a-ClO4, in agreement
with the kinetic analysis above. The reactions of 1a and 1b
described in Scheme 2 therefore include the weakest nucleo-
philes so far combined with flavylium ions, indicating that
the synthetic potential of these electrophiles has not been
fully exhausted.
Experimental Section
General: NMR: Varian Mercury 200, Bruker ARX 300, Varian
VRX 400S, and Varian INOVA-400. 1H NMR chemical shifts refer
to TMS (δH ϭ 0.00) and 13C NMR chemical shifts refer to the
solvent as internal standard ([D3]chloroform δ ϭ 77.0; [D3]aceto-
nitrile δ ϭ 1.3); IR: IR spectrophotometer 325 (PerkinϪElmer).
MS: Varian MAT 90 and MAT 95. Ϫ Melting points (uncorrected):
Reichert Thermovar. All reactions were performed under an atmos-
phere of dry nitrogen. Dichloromethane was freshly distilled from
CaH2 before use. THF and diethyl ether were dried over KOH and
Figure 1. Comparison of the electrophilicities of flavylium ions
with reagents of similar reactivity
Eur. J. Org. Chem. 2001, 4451Ϫ4456
4453

C. Fichtner, G. Remennikov, H. Mayr
FULL PAPER
Na/benzophenone, pentane was dried over KOH and Na. The allyl-
BF4 (522 mg, 1.35 mmol) in CH2Cl2 (10 mL). After 1 min the mix-
silane 4 was prepared as described in ref.,[15b] and 2a, 3, 5 and 6 ture was quenched with sat. aq. NaHCO3 (20 mL). The organic
are commercially available. The kinetic measurements and the data phase was then separated, and the aqueous phase was extracted
evaluation were carried out as described previously.[15a]
with CH2Cl2 (1 ϫ 10 mL). The combined organic layers were dried
(MgSO4) and the solvent was evaporated. The residue was purified
by column chromatography (silica gel, hexane/diethyl ether ϭ 8:1)
to yield 7b (225 mg, 70%). The 1H NMR spectrum was in agree-
ment with the data described in ref.[11b]
Flavylium Tetrafluoroborate (1a-BF4): Salicylideneacetophenone 2a
(1.20 g, 5.25 mmol) was suspended in dry diethyl ether (60 mL) un-
der a nitrogen atmosphere and the mixture was heated to reflux.
Upon addition of 10 equiv. HBF4·OEt2 the solid dissolved and the
solution turned red. The mixture was heated for 21 h and cooled
to ambient temperature to yield a precipitate which was collected
under N2, washed with dry diethyl ether and dried in vacuo.
Recrystallization yielded 1a-BF4 (1.01 g, 64%) as a yellow powder,
m.p. 100 °C (dec., from CH2Cl2/pentane). 1H NMR (CD3CN,
600 MHz): δ ϭ 7.78Ϫ7.84 (m, 2 H, 3Ј-H, 5Ј-H), 7.93Ϫ7.99 (m, 1
H, 4Ј-H), 8.01Ϫ8.06 (m, 1 H, 6-H), 8.37Ϫ8.40 (m, 3 H, 5-H, 7-H,
8-H), 8.55Ϫ8.59 (m, 2 H, 2Ј-H, 6Ј-H), 8.73 (d, J ϭ 9.0 Hz, 1 H, 3-
H), 9.50 (d, J ϭ 9.0 Hz, 1 H, 4-H). These data are identical to
4-(2-Methylallyl)-2-phenyl-4H-chromene (8a): A solution of (2-
methylallyl)trimethylsilane (4; 52 µL, 38 mg, 0.30 mmol) in 3 mL
CH2Cl2 was added to 1a-BF4 (80 mg, 0.28 mmol). After stirring
for 2 h at ambient temperature, the solvent was evaporated. The
residue was purified by column chromatography (silica gel, CHCl3)
1
to yield 8a (70 mg, 90%). H NMR (300 MHz, CDCl3): δ ϭ 1.80
2
3
4
(s, 3 H, 2Ј-CH3), 2.35 (ddd, J ϭ 13.5 Hz, J1AЈ,4 ϭ 9.3 Hz, J ϭ
2
3
0.8 Hz, 1 H, 1Ј-HA), 2.50 (dd, J ϭ 13.5 Hz, J1BЈ,4 ϭ 5.0 Hz, 1 H,
3
3
3
1Ј-HB), 3.75 (ddd, J4,1AЈ ϭ 9.3 Hz, J4,1BЈ ϭ J4,3 ഠ 4.7 Hz, 1 H,
4-H), 4.72, 4.87 (2 br. s, 2 ϫ 1 H, 3Ј-H2), 5.53 (d, J ϭ 4.7 Hz, 1 H,
3-H), 7.00Ϫ7.41 (m, 7 H, Ar), 7.67Ϫ7.70 (m, 2 H, Ar); 13C NMR
(75.5 MHz, CDCl3): δ ϭ 22.7 (q, 2Ј-CH3), 32.6 (d, C-4), 48.5 (t,
C-1Ј), 100.2 (d, C-3), 113.2 (t, C-3Ј), 116.5, 123.2 (2 d, Ar), 124.2
(s, Ar), 124.7, 127.4, 128.26, 128.30, 128.37 (5 d, Ar), 134.5, 142.4,
148.3, 151.7 (4 s, C-2Ј and Ar). Signal assignments are based on
those described in ref.[25] 13C NMR (CD3CN, 150 MHz): δ ϭ 118.5
;
(d, C-3), 119.9 (d, C-8), 125.3 (C-10), 129.2 (C-1Ј), 130.9 (d, C-3Ј),
131.0 (d, C-2Ј), 131.2 (d, C-6), 131.3 (d, C-5), 138.3 (d, C-4Ј), 140.8
(d, C-7), 157.2 (C-9), 158.5 (d, C-4), 176.4 (C-2). 13C NMR spectro-
scopic data are identical to those described in ref.[26]; IR (KBr):
ν˜ ϭ 1620 cmϪ1, 1590, 1549, 1523, 1456, 1342, 1124, 1084; MS (EI):
m/z (%) ϭ 207 (100) [Mϩ], 178 (24).
1
1
1
13
Ϫ1
˜
H, H and H, C-COSY experiments; IR (KBr): ν ϭ 3070 cm
,
3037, 2968, 2928, 1646, 1584, 1487, 1456, 1449, 1235, 1114, 1045,
Flavylium Triflate (1a-OTf): This compound was synthesized as de-
scribed for 1a-BF4 from 2a (2.00 g, 8.91 mmol) and CF3SO3H
(2.6 mL, 30 mmol) in diethyl ether (50 mL): 2.03 g (64%) as a yel-
low powder, m.p. 121Ϫ123 °C (dec., from CH2Cl2/pentane). The
1H NMR spectrum agreed with that obtained for 1a-BF4;
C16H11F3O4S (356.32): calcd. C 53.93, H 3.11, S 8.99; found C
54.27, H 3.21, S 8.38.
757, 694; MS (EI): m/z (%) ϭ 262 (8) [Mϩ], 207 (100), 178 (26).
4Ј-Methoxyflavylium Tetrafluoroborate (1b-BF4):[10] A suspension
of 2b (0.87 g, 3.4 mmol) in dry THF (40 mL) was heated to reflux
under nitrogen atmosphere. Upon addition of 10 equiv. HBF4·OEt2
the solid dissolved and the solution turned red. The mixture was
heated for 18 h and cooled to ambient temperature to yield a pre-
cipitate which was collected under N2, washed with dry diethyl
ether and dried in vacuo. Recrystallization yielded 1b-BF4 (0.684 g,
62%) as an orange powder, m.p. 170 °C (dec., from CH2Cl2/pen-
tane). NMR spectroscopic data agreed with those published in
2-(4-Methoxyphenyl)-4-(2-methylallyl)-4H-chromene (8b): A solu-
tion of (2-methylallyl)trimethylsilane (4; 0.147 mL, 0.109 g,
0.848 mmol) in CH2Cl2 (5 mL) was added to 1b-BF4 (0.25 g,
0.80 mmol). After stirring for 2 h at ambient temperature, the sol-
vent was evaporated. The residue was purified by column chroma-
tography (silica gel, CHCl3) to yield 8b (80 mg, 34%). 1H NMR
(200 MHz, CDCl3): δ ϭ 1.81 (s, 3 H, 2Ј-CH3), 2.34 (ddd, 2J ϭ
13.0 Hz, J1AЈ,4 ϭ 9.3 Hz, J Ͻ 1 Hz, 1 H, 1Ј-HA), 2.50 (dd, J ϭ
13.2 Hz, 3J1BЈ,4 ϭ 5.0 Hz, 1 H, 1Ј-HB), 3.69Ϫ3.83 (m, 4 H, 4-H and
OMe), 4.72, 4.86 (2 br. s, 2 ϫ 1 H, 3Ј-H2), 5.41 (d, J ϭ 4.6 Hz, 1
H, 3-H), 6.73Ϫ7.20 (m, 6 H, Ar), 7.58Ϫ7.66 (m, 2 H, Ar).
refs.[10,26b]; IR (KBr): ν ϭ 1619 cmϪ1, 1604, 1589, 1536, 1503, 1456,
˜
1352, 1277, 1184, 1084; MS (EI): m/z (%) ϭ 237 (100) [Mϩ], 222
(7), 194 (17), 165 (9).
3
4
2
4Ј-Methoxyflavylium Triflate (1b-OTf):This compound was synthe-
sized as described for 1b-BF4 from 2b (2.00 g, 7.87 mmol) and
CF3SO3H (2.0 mL, 23 mmol) in THF (40 mL): 2.04 g (67%). Or-
ange powder, m.p. 218Ϫ219 °C (dec., from CH2Cl2/pentane). The
1H NMR spectrum agreed with that obtained from 1a-BF4;
C17H13F3O5S (386.35): calcd. C 52.85, H 3.39, S 8.30; found C
52.55, H 3.41, S 8.04.
2-(2-Phenyl-4H-chromen-4-yl)cyclohexanone (9): At ambient tem-
perature the silyl enol ether 5 (583 µL, 516 mg, 3.03 mmol) was
added to a solution of 1a-BF4 (818 mg, 2.78 mmol) in CH2Cl2
(15 mL). After stirring for 20 min the solvent was evaporated in
vacuo. The residue was purified and separated by column chroma-
tography (silica gel, CHCl3) to yield two fractions: 0.12 g of 7a
(21%) and 0.09 g of 9 (11%, as a mixture of diastereomeric products
in a ratio of 79:21, determined by 1H NMR spectroscopy). 1H
NMR (400 MHz, CD3CN): δ ϭ 1.48Ϫ1.67, 1.73Ϫ1.78 (2 m, 4 H
ϩ 1 H, 3Ј-H2, 4Ј-H2, 5Ј-H), 1.96Ϫ2.04 (m, 1 H, 5Ј-H), 2.35Ϫ2.41
(m, 2 H, 6Ј-H2), 2.73Ϫ2.78 (m, 1 H, 2Ј-H), 4.31 (dd, J ϭ 4.7,
3.1 Hz, 1 H, 4-H), 5.61 (d, J ϭ 4.8 Hz, 1 H, 3-H), 7.03Ϫ7.12 (m,
2 H, ArH), 7.19Ϫ7.26 (m, 2 H, ArH), 7.36Ϫ7.44 (m, 3 H, ArH),
7.69Ϫ7.74 (m, 2 H, ArH). Additional signals of the minor diaster-
2-Phenyl-4H-chromene (7a): At Ϫ40 °C tributylstannane 3 (0.58 g,
1.99 mmol) was added to a solution of 1a-BF4 (0.54 g, 1.84 mmol)
in CH2Cl2 (10 mL). After 2 min the mixture was quenched with
sat. aq. NaHCO3 (20 mL). The organic layer was separated and
dried (MgSO4). The solvent was evaporated in vacuo and the res-
idue was purified by column chromatography (alumina I, hexane/
diethyl ether ϭ 4:1) to yield 7a (0.25 g, 65%), m.p. 51Ϫ52 °C
(ref.:[27] 52Ϫ53 °C). The obtained 1H NMR spectrum was in agree-
ment with the data described in ref.[28]
2-(4Ј-Methoxyphenyl)-4H-chromene (7b): At Ϫ40 °C tributylstan-
nane 3 (0.40 mL, 0.44 g, 1.5 mmol) was added to a solution of 1b- eomer: δ ϭ 2.58Ϫ2.62 (m, 1 H, 2Ј-H), 4.18 (t, J ϭ 4.8 Hz, 1 H,
4454 Eur. J. Org. Chem. 2001, 4451Ϫ4456

Kinetics of the Reactions of Flavylium Ions with π-Nucleophiles
FULL PAPER
4-H), 5.66 (d, J ϭ 5.4 Hz, 1 H, 3-H); 13C NMR (100.6 MHz,
CD3CN): δ ϭ 24.73 (t, C-3Ј or C-4Ј), 27.20 (t, C-5Ј), 27.93 (t, C-
3Ј or C-4Ј), 33.59 (d, C-4), 41.96 (t, C-6Ј), 57.83 (d, C-2Ј), 98.41 (d,
C-3), 116.35 (d, Ar), 122.94 (s, Ar), 124.03, 124.66, 127.94, 128.22,
128.66, 128.76 (6 d, Ar), 134.31, 149.65, 152.75 (3 s, Ar), 211.01 (s,
CϭO). Additional signals of the minor diastereomer: δ ϭ 24.81 (t),
27.23 (t), 29.31 (t), 33.51 (d), 42.12 (t), 57.94 (d), 101.04 (d), 149.8
(s), 153.01 (s). Signal assignments are based on gDQCOSY and
gHSQC experiments; MS (EI, 70 eV), m/z (%) ϭ 305 (8), 304 (11)
[Mϩ], 211 (17), 208 (16), 207 (100), 185 (11).
Acknowledgments
Financial support of the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie is gratefully acknowledged.
[1]
C. Czerney, H. Hartmann, in Methoden Org. Chem. (Houben-
Weyl), 4th ed., Vol. VII/2Ea (Ed.: R. P. Kreher), Thieme Ver-
lag, Stuttgart, 1991, pp. 30Ϫ41.
[2] [2a]
G. A. Iacobucci, J. G. Sweeny, Tetrahedron 1983, 39,
3005Ϫ3038; [2b] O. Dangles, H. Elhajji, Helv. Chim. Acta 1994,
77, 1595Ϫ1610.
[3]
P. Czerney, G. Graness, E. Birckner, F. Vollmer, W. Rettig, J.
Photochem. Photobiol. A 1995, 89, 31Ϫ36.
[4] [4a]
S. Maruyama, T. Kubota, K. Kojima, H. Tamura, M. Ha-
[4b]
rada, Ger. Offen. 2,230,303, Chem. Abstr. 1973, 79, 414;
T.
Kubota, K. Kojima, M. Ohta, Ger. Offen. 2,249,448, Chem.
Abstr. 1974, 80, 406.
[5]
[5a] F. Pina, M. J. Melo, M. Maestri, P. Passaniti, N. Comaioni,
[5b]
V. Balzani, Eur. J. Org. Chem. 1999, 3199Ϫ3207;
F. Pina,
M. Maestri, V. Balzani, Chem. Commun. 1999, 107Ϫ114; [5c] F.
Pina, A. Roque, M. J. Melo, M. Maestri, L. Belladelli, V. Bal-
1-Phenyl-2-(2-phenyl-4H-chromen-4-yl)ethanone (10a) and 1-
Phenyl-2-(2-phenyl-4H-chromen-4-ylidene)ethanone (11a): A solution
of the silyl enol ether 6 (0.23 mL, 0.22 g, 1.1 mmol) in CH2Cl2
(10 mL) was added to 1a-BF4 (0.22 g, 0.78 mmol). After stirring
for 2 h the solvent was evaporated and the residue was purified and
separated by column chromatography (silica gel, CHCl3) to yield
10a (0.03 g, 12%) and 11a (0.12 g, 47%).
[5d]
zani, Chem. Eur. J. 1998, 4, 1184Ϫ1191;
F. Pina, M. H.
Melo, M. Maestri, R. Ballardini, V. Balzani, J. Am. Chem. Soc.
1997, 119, 5556Ϫ5561.
[6]
[7]
R. A. McClelland, S. Gedge, J. Am. Chem. Soc. 1980, 102,
5838Ϫ5848.
[7a] H. Mayr, M. Patz, Angew. Chem. 1994, 106, 990Ϫ1010; An-
[7b]
10a: 1H NMR (CDCl3, 400 MHz): δ ϭ 3.34 (JAB ϭ 17.2 Hz, JAX ϭ
4.7 Hz, 1 H, 1Ј-HA), 3.42 (JAB ϭ 17.2 Hz, JBX ϭ 8.8 Hz, 1 H, 1Ј-
HB), 4.35 (v. quint, J ϭ 4.7 Hz, 1 H, 4-H), 5.70 (d, J ϭ 4.9 Hz, 1
H, 3-H), 7.02Ϫ7.57 (m, 14 H, ArH); MS (EI): m/z (%) ϭ 326 (16)
[Mϩ], 325 (16), 324 (55), 274 (53), 207 (100), 105 (13), 77 (7).
11a: 1H NMR (CDCl3, 200 MHz): δ ϭ 7.15 (s, 1 H, 3-H),
7.28Ϫ7.62 (m, 10 H, ArH), 7.96Ϫ8.08 (m, 4 H, ArH), 8.95 (s, 1 H,
1Ј-H);[29] MS (EI): m/z (%) ϭ 324 (100) [Mϩ], 323 (44), 247 (70).
gew. Chem. Int. Ed. Engl. 1994, 33, 938Ϫ957;
H. Mayr, O.
Kuhn, M. F. Gotta, M. Patz, J. Phys. Org. Chem. 1998, 11,
642Ϫ654; [7c] H. Mayr, M. Patz, M. F. Gotta, A. R. Ofial, Pure
[7d]
Appl. Chem. 1998, 70, 1993Ϫ2000;
In this work we have
used the revised reactivity parameters from ref.[16]
[8]
`
R. J. W. LeFevre, J. Chem. Soc. 1929, 2771Ϫ2774.
[9] [9a]
For details of preparation, see: C. Fichtner, Dissertation,
[9b]
Ludwig-Maximilians-Universität München 2001;
See also:
E. Maccarone, G. Cuffari, A. Passerini, F. Raymo, J. Chem.
Res. (S) 1991, 240Ϫ241; J. Chem. Res. (M) 1991, 2401Ϫ2413.
A. R. Katritzky, P. Czerney, J. R. Levell, W. Du, Eur. J. Org.
Chem. 1998, 2623Ϫ2629.
[10]
2-(2-(4-Methoxyphenyl)-4H-chromen-4-yl)-1-phenylethanone (10b)
and 2-(2-(4-Methoxyphenyl)-4H-chromen-4-ylidene)-1-phenyletha-
none (11b):
[11] [11a]
G. A. Reynolds, J. A. VanAllan, J. Org. Chem. 1967, 32,
[11b]
3616Ϫ3618;
J. W. Clark-Lewis, M. I. Baig, Aust. J. Chem.
1971, 24, 2581Ϫ2592.
A. Cornelson, S. v. Konstanecki, Ber. Dtsch. Chem. Ges. 1896,
29, 240Ϫ244.
[12]
[13]
[14]
Method A: Within 10 min
a solution of 1b-BF4 (163 mg,
0.503 mmol) was added to a solution of the silyl enol ether 6
(305 mg, 1.59 mmol) in CH2Cl2 (5 mL). The mixture was stirred
for 22 h at ambient temperature, then the solvent was evaporated
and the residue was subjected to column chromatography (neutral
alumina I, hexane/diethyl ether ϭ 2:1) to yield 10b (30%) and 11b
(18%) in separate fractions which were still contaminated with ace-
tophenone.
J. A. VanAllan, G. A. Reynolds, T. H. Regan, J. Org. Chem.
1967, 32, 1897Ϫ1899.
D. W. Hill, J. Chem. Soc. 1934, 1255Ϫ1258.
[15] [15a]
H. Mayr, R. Schneider, C. Schade, J. Bartl, R. Bederke, J.
[15b]
Am. Chem. Soc. 1990, 112, 4446Ϫ4454;
Mayr, J. Am. Chem. Soc. 1991, 113, 4954Ϫ4961;
feindt, M. Patz, M. Müller, H. Mayr, J. Am. Chem. Soc. 1998,
120, 3629Ϫ3634.
H. Mayr, T. Bug, M. F. Gotta, N. Hering, B. Irrgang, B. Janker,
B. Kempf, R. Loos, A. R. Ofial, G. Remennikov, H. Schimmel,
J. Am. Chem. Soc. 2001, 123, 9500Ϫ9512.
G. Hagen, H.
[15c]
J. Bur-
10b: 1H NMR (CDCl3, 200 MHz): δ ϭ 3.24Ϫ3.46 (m, 2 H, 1Ј-H2),
3.79 (s, 3 H, OMe), 4.31 (mc, 1 H, 4-H), 5.56 (d, J ϭ 4.9 Hz, 1 H,
3-H), 6.80Ϫ7.90 (m, 13 H, ArH); MS (EI): m/z (%) ϭ 356 (3) [Mϩ],
237 (100).
[16]
[17] [17a]
M. Roth, H. Mayr, Angew. Chem. 1995, 107, 2428Ϫ2430;
[17b]
Angew. Chem. Int. Ed. Engl. 1995, 34, 2250Ϫ2252;
H.
Method B: A solution of the nucleophile 6 (0.228 mL, 0.214 g,
1.11 mmol) in CH2Cl2 (10 mL) was added to neat 1b-BF4 (0.30 g,
0.93 mmol). After stirring for 2 h the solvent was evaporated and
the residue was purified by column chromatography (silica gel,
CHCl3) to yield 11b (0.12 g, 36%): m.p. 138Ϫ140 °C; 1H NMR
(CDCl3, 200 MHz): δ ϭ 3.86 (s, 3 H, OMe), 6.95Ϫ7.05 (m, 2 H,
ArH), 7.10 (s, 1 H, 3-H), 7.26Ϫ7.53, 7.93Ϫ8.05 (2 m, 6 H ϩ 5 H,
ArH), 8.89 (s, 1 H, 1Ј-H); MS (EI): m/z (%) ϭ 354 (100) [Mϩ], 353
(40), 277 (58); C24H18O3 (354.14): calcd. C 81.34, H 5.12; found C
81.43, H 5.06.
Mayr, G. Gorath, J. Am. Chem. Soc. 1995, 117, 7862Ϫ7868.
[18] [18a]
A. Löwenbein, E. Pongracz, E. A. Spiess, Ber. Dtsch.
Chem. Ges. 1924, 57, 1517Ϫ1525; [18b] A. V. Koblik, L. A. Mur-
ad’yan, E. S. Luk’yanov, Zh. Org. Khim. 1996, 32, 919Ϫ924;
Russ. J. Org. Chem. 1996, 32, 887Ϫ892.
[19]
[20]
[21]
R. Lucius, R. Loos, H. Mayr, Angew. Chem., in print.
´
F. Kröhnke, K. Dickore, Chem. Ber. 1959, 29, 46Ϫ62.
D. H. Wadsworth, M. R. Detty, B. J. Murray, C. H. Weidner,
N. F. Haley, J. Org. Chem. 1984, 49, 2676Ϫ2681.
L. Jurd, J. Heterocycl. Chem. 1981, 26, 2857Ϫ2862.
E. T. Ostensen, Acta Chem. Scand., Ser. B 1975, 29, 789Ϫ790.
[22]
[23]
Eur. J. Org. Chem. 2001, 4451Ϫ4456
4455

C. Fichtner, G. Remennikov, H. Mayr
FULL PAPER
[24]
[28]
[29]
M. F. Gotta, H. Mayr, J. Org. Chem. 1998, 63, 9769Ϫ9775.
M. M. Mishrikey, E. T. Østensen, Acta Chem. Scand., Ser. B
1976, 30, 329Ϫ335.
[25]
G. Cardillo, R. Cricchio, L. Morlini, Tetrahedron Lett. 1969,
907Ϫ908.
For analytical data of 11a, see also: L. A. Murad’yan, A. V.
Koblik, D. S. Yufit, Yu. T. Struchkov, V. G. ArsenЈev, S. M.
Luk’yanov, Zh. Org. Khim. 1996, 32, 925Ϫ933; Russ. J. Org.
Chem. 1996, 32, 893Ϫ901.
[26] [26a]
P. L. Desbene, J. C. Cherton, Tetrahedron 1984, 40,
[26b]
3567Ϫ3571;
M. Gruner, H. Hartmann, P. Czerney, J.
Prakt. Chem. 1990, 332, 461Ϫ469.
T. G. C. Bird, B. R. Brown, I. A. Stuart, A. W. R. Tyrrell, J.
Chem. Soc., Perkin Trans. 1 1983, 1831Ϫ1846.
[27]
Received June 13, 2001
[O01281]
4456
Eur. J. Org. Chem. 2001, 4451Ϫ4456