**2. Results and Discussion**

The synthetic route used to obtain 1,3-dithiolium flavonoids **5a**–**e** is described in Scheme 1 and follows the protocol used for the model compound **5a**. 2-Bromo-1-(2-hydroxy-3,5-diiodophenyl)ethan-1-one (**1**) [18] readily underwent nucleophilic substitution in the presence of the *N,N*-diethyldithiocarbamate anion, in acetone, yielding the desired phenacyl carbodithioate **2**. The incorporation of the *N,N*-diethyldithiocarbamic unit was confirmed by NMR spectral data. Thus, the 1H NMR spectrum indicated the presence of two triplets, at 1.30 ppm and 1.38 ppm, corresponding to the two methyl groups, and also two quartets, 3.83 ppm and 4.03 ppm, provided by the two methylene units directly bound to the nitrogen atom. The 13C NMR spectrum confirmed the presence of the two methyl groups (11.5 ppm and 12.6 ppm), the two nitrogen-bounded methylene groups (47.3 ppm and 50.5 ppm) and the thiocarbonyl carbon atom (192.8 ppm).

**Scheme 1.** The synthesis of tricyclic flavonoids **5a**–**e** from flavanones **4a**–**e**. The later have been obtained starting from phenacyl bromide **1** through dithiocarbamate **2** and aminals **3a**–**e**.

The reaction of 1-(2-hydroxy-3,5-diiodophenyl)-1-oxa-ethan-2-yl *N,N*-diethylaminocarbodithioate (**2**) with aminals **3** provided 3-substituted dithiocarbamic flavanones **4a**–**e** as a mixture of diastereoisomers (Scheme 1). Aminals **3** were synthesized according to the literature procedures [19,20]. Due to the low solubility of dithiocarbamate **2** in ethanol, an improved experimental procedure using a mixture of chloroform and methanol (1:1) as solvent was developed. Thus, the homogeneous reaction mixture was heated at reflux for 4 h. After cooling, pale yellow precipitates were formed that were filtered, dried and recrystallized from ethanol to provide 3-dithiocarbamic flavanones **4a**–**e**, as an inseparable mixture of diastereoisomers, in 68–80% yields. NMR spectra supported the benzopyran ring closure. Thus, besides the NMR pattern of *para*-substituted aromatic ring originating from aminal **3**, we observed the disappearance of the signal of the methylene group from dithiocarbamate **2** (4.86 ppm) and the presence of the characteristic pattern of vicinal hydrogen atoms at the C-2 and C-3 positions of the benzopyran ring for both diastereoisomers between 5.7 and 6 ppm. Because these two protons can be located either on the same side or on opposite sides of the plane of the molecule, two stereoisomers, *anti*-**4** and *syn*-**4**" can be obtained (Figure 1). The relative orientation of the two hydrogen atoms would, of course, be expected to have an influence on the magnitude of their coupling constants. The *anti* isomers always displayed a coupling constant between 6.2 and 7.3 Hz and the *syn* isomers around 4 Hz. The coupling constants and diastereoisomeric ratios of flavonoids **4a**–**e** are presented in Table 1. A 13C NMR analysis confirmed the presence of the C-2 carbon atom, found around 80.0 ppm, while the C-3 carbon atom could be found around 60.0 ppm.

*anti*

*syn*

**Figure 1.** Diastereoisomers of flavonoids **4a**–**e**.

**Table 1.** Coupling constants H-2–H-3 and diastereoisomers ratio of flavanones **4a**–**e**.


α-Ketodithiocarbamates are valuable precursors for 2-dialkylamino-1,3-dithiolium-2-yl cations [21–23]. Usually, the acid-catalysed cyclocondensation of these substrates is the method employed for the synthesis of the desired 1,3-dithiolium cations. This consisted in using a glacial acetic acid/sulfuric acid 3:1 (*v*/*v*) at 80 ◦C for 10 min [24]. Previously, we developed specific methods for the sensitive starting materials prone to decomposition under regular reaction conditions. In one such application, a mixture of phosphorus pentoxide–methanesulfonic acid 1:10 (*w*/*v*) was used for the synthesis of several 4-iodoaryl-1,3-dithiolium salts [25].

Despite our previous experience with the synthesis of tricyclic flavonoids of type **5** [13,14,17], attempts to close the 1,3-dithiolium ring on flavanones **4** led to a black intractable material. Even under mild reaction conditions described by us for iodinesubstituted phenacyl dithiocarbamates [25,26], the cyclization reactions failed for all new reported flavanones **4**. Consequently, we tuned the reaction conditions in terms of reducing the reaction temperature and the composition of the cyclization mixture. The best results for our substrates were obtained using a mixture of glacial acetic acid/sulfuric acid 1:1 (*v*/*v*) at 40 ◦C for 30 min, followed by a treatment with an aqueous solution of sodium

tetrafluoroborate. Thus, the tricyclic 1,3-dithiolium flavonoids **5** was obtained as white crystals in 80–88% yields.

The cyclization of dithiocarbamates **4** to tricyclic flavonoids **5** was accompanied by important spectral changes. Thus, IR spectroscopy showed the absence of the carbonyl absorption bands (1690–1700 cm<sup>−</sup>1) and the presence of new strong and broad absorption bands (ca. 1070 cm−1) from the tetrafluoroborate anion. In the 1H NMR spectra, the doublets corresponding to the C-3 hydrogens disappeared; at the same time, the signals of the C-2 hydrogens were shifted to ca. 6.9 ppm and became singlets. The 13C NMR spectra confirmed the absence of the carbonyl and thiocarbonyl atoms and showed a new signal at ca. 185 ppm corresponding to the 1,3-dithiol-2-ylium carbon atom.

## **3. Materials and Methods**
