Beilstein J. Org. Chem. 2020, 16, 2026–2031.
(
V2O5), PIFA, and PIDA, in addition to SnCl4, were consid- verted quantitatively to binaphthyl 16 in the presence of an
because of its implication in single-electron oxidation [24], and thylquinone 16 was synthesized through the oxidation of
tion state, should be able to facilitate single-electron transfer in methylation [25]. The cyclization of binaphthyl 16 was then
the presence of electron-rich arenes.
binaphthyls to form pentacyclic furan derivatives [8,18,22].
The dimerization of 1,2,4-trimethoxynaphthalene (17) in the However, the photolytic cyclization of binaphthyl 16 using a
presence of the metal oxidants CAN, V2O5, and CrO3, afforded 100 W bulb was attempted without success, due to degradation
binaphthyl 16 in 29, 34, and 19% yields, respectively (Table 1). of the starting material. This led to a different approach employ-
As anticipated, the reaction of naphthalene 17 with CAN under ing a reductive, base-mediated cyclization using alkaline
aqueous conditions resulted in preferential oxidative demethyla- aqueous sodium dithionite. Interestingly, the typical conditions
tion to give quinone 7, as opposed to oxidative dimerization. for reduction using dithionite proved too harsh for the substrate,
The elimination of water from the reaction posed a few chal- and like the photolysis of the binaphthyl 16, degradation
lenges since the solubility of CAN in organic solvents deter- occurred. However, the use of triethylamine instead of aqueous
mines the likelihood of nitration or oxidative dimerization [1]. It sodium hydroxide resulted in the isolation of balsaminone A (4)
was found that dry acetonitrile was more conducive to nitration, in 13% yield, an overall 7–8% yield over 3 steps, completing
contrast to CAN, both V2O5 and CrO3 required aqueous condi- Scheme 5.
tions to prevent complexation of the reagent and the starting
the most effective oxidant for dimerization (Table 1). However, With the synthesis of balsaminone A (4) accomplished, the
the hypervalent iodine reagents PIFA and PIDA gave better direct biomimetic synthesis of ellagic acid (5) was targeted.
in 48% yield over four steps by Alam et al. [23], starting
from methyl gallate (15), it was anticipated that a more
Following the successful oxidative dimerization of 1,2,4- concise and efficient synthesis could be attained. Methyl
trimethoxynaphthalene 17 to biaryl 18, the biaryl was con- gallate (15), which may be obtained commercially or from the
Table 1: Reagents and products in the oxidative dimerization of 1,2,4-trimethoxynaphthalene (17).
16 (%)
18 (%)
7 (%)
CANa
29b
34
19
15
–
55c
–
67b
–
V2O5a,b
CrO3a,b
–
62
–
FeCl3·SiO2a,c
FeCl3·6H2Oa,c
SnCl4d
43
8
–
22
21
12
13
48d
59
63
–
–
PIDA, BF3·OEt2e,f
PIFA, BF3·OEt2e,f
IBX, BF3·OEt2e,f
–
–
45
aReaction of naphthalene 17 (0.5 mmol) with oxidant (1.65 mmol) at rt. bAddition of oxidant in H2O (1 mL, dropwise) to substrate in CH3CN or CH3OH
1 mL). cAddition of oxidant (neat) in thirds, to substrate dissolved in CH3CN. dReaction was carried out in CH2Cl2 at 100 °C in a sealed tube.
eReaction of naphthalene 17 (0.5 mmol) with oxidant (0.65 mmol). fReaction carried out under N2.
(
2029