H. Zhang, Q. Wang, L. Huang et al.
Tetrahedron Letters 72 (2021) 153070
Scheme 2. Synthesis of Wrightiadione.
yield, entry 3) and Sc(OTf)3 also gave unsatisfactory result (31.0%
yield, entry 4). Further regulating the reaction conditions were
achieved with FeCl3, which worked to yield 2a in moderate yield
(entry 5). To our delight, when FeCl3 reagent was increased to
0.5 equivalent, a dramatic improvement in the yield was achieved
(87.7% yield, entry 6). Then, considering the impact of water, FeCl3
(0.5 eq) was added separately after reaction time 8 h, the yield was
no obvious improved (entry 7). It should be noted that, increasing
equivalent of FeCl3, prolonging reaction time and increasing reac-
tion temperature did not improve the yield, but rather led to a
decreased yield (entry 8, 9 and 10). Finally, the optimal condition
was carried out in O-DCB with 2.4 eq. SeO2 and 0.5 eq. FeCl3 at
150 °C, after 12 h the desired transformation was successfully
demonstrated.
Fig. 1. Biologically active indanone derivatives.
With optimal conditions determined, our focus was directed
toward studying the substrates in the presence of 2.4 eq. SeO2
and 0.5 eq. FeCl3. The substituents on R1 and R2 were investigated
to see the substituent effect on the reactivity (Table 2). The tetra-
cyclic scaffold could be easily equipped with an additional sub-
stituent at R1 and R2 by this one-pot process. It was noticed that
even the present of aryl group bearing either electron-donating
or withdrawing group at R2, such as an alkyl (methyl and ethyl
group), methoxy (2f, 2j) and halogen (2e), the reactions were
well-tolerated and generated the respective heteroindanones in
moderate yields. The molecular structure of compound 2g was
independently confirmed by X-ray crystal structure analysis [18].
Evidently, the effect of the steric and electronic charactersof the
substituent R1 was not distinct on the course of the reaction (2h-
2u). In addition, amenable to this protocol, nitrogen-containing
derivatives were also investigated, and the expected products
(2v-2y) were obtained in moderate yields (Table 2).
Fig. 2. X-ray crystal structure of 2g.
Specially, Wrightiadione which is an indanone derivative
including a similar indanone fused heterocyclic structure, isolated
from the bark of Wrightia tomentosa medicinally in Thailand.
Based on the above studies, we envisioned that application of this
one-pot approach reaction to produce the natural product starting
from simple starting materials such as readily available 2-Methyl-
chromone. In the synthetic route, iodination with CAN and I2 was
occurred firstly. Then, the Suzuki-Miyaura coupling of the resulting
iodide with phenylboronic acid gave the desired compound in 90%
overall yield. Satisfactorily, the desired product was produced
smoothly via this one-pot procedure.
With these results, the reaction mechanism was shown in
Scheme 3. Formation of the generated aldehyde (a) was carried
out with the corresponding 2-methyl-thiochromones (1) following
Riley selenium dioxide oxidation. The selenous acid generated
from SeO2 and H2O, which was provided during Riley allylic
oxidation. Next, under acid condition, promoted by FeCl3 and
selenous, the tetracyclic core (b) was generated by intramolecular
Scheme 1. One-pot pathway to access indanone fused heterocyclic compounds.
acids in order to produce indanone fused heterocyclic compounds
(Table 1).
In the initial attempt, As shown in entry1, in the presence of 2.4
equiv SeO2 and 0.1 equiv BF3ꢀOEt2 in o-dichlorobenzene (O-DCB)
the reaction proceeded at 150 °C within 12 h to give desired inda-
none 2a as a sole product (34.7% yield, entry 1). AlCl3 showed sim-
ilar reactivity and gave similar result (41.0% yield, entry 2). Tin
tetrachloride (SnCl4) resulted in a much lower yield of 2a (17.2%
2
Zhang, Huan
