Dodecabromo‐ and Dodecaiodocentrohexaindane: T_d‐Symmetrical Key Building Blocks for Twelve‐Fold Cross‐Coupling Reactions and Six‐Fold Orthogonal Extension

Abstract

Centrohexaindane was converted into its T -symmetrical 2,3,6,7,10,11,14,15,20,21,26,27-dodecabromo and -dodecaiodo derivatives using N-bromo- and N-iodosuccinimide, respectively, in the presence of trifluoromethanesulfonic acid as a catalyst in single, highly efficient steps. Sonication or microwave irradiation was indispensable to enforce exhaustive halogenation of the twelve equivalent peripheral positions of this Cartesian polyaromatic hydrocarbon. Despite their extremely poor solubility in most organic solvents, the new dodecahalo derivatives were fully characterized, including single crystal X-ray structure analysis. Subsequent Pd -catalyzed twelve-fold C-C cross-coupling reactions furnished the corresponding dodecamethyl, dodeca(phenylethynyl) and dodecaphenyl derivatives in good to excellent yields. The latter hydrocarbon was also analyzed by X-ray diffraction.

A Perspective on Centrohexaindane Chemistry and a Deep‐Sleeping “Cartesian” Seed

“…Also remarkable is the fact that mass spectrometric characterization of both 53 and 54 required electrospray ionization in the negative-ion mode (ESI-(À )), generating the [M + Cl]molecular adduct ions, obviously reflecting the high electron or anion affinity of the highly halogenated and compact molecular species. [57] In spite of the critically low solubility of the dodecahalo compounds 53 and 54, 12-fold C-C cross coupling reactions were carried out with success. It was anticipated that, upon progressing substitution of the halogen functionalities, solubil- ing dodecaphenylcentrohexaindane 57 in good yield (63 %).…”

“…[52] Alteratively, post-functionalization of the parent hydrocarbon 5 was achieved using drastic halogenation conditions, which paved the way to the first congeners bearing twelve hydrocarbon substituents at the molecular periphery. [57] Scheme 7. Potential complementary accesses to the hypothetical octamethoxycentrohexaindane 49 that bears functional groups both at the molecular periphery and in each of the four [3.3.3]propellane cavities, along the fenestrane route.…”

“…Interestingly, when the less acidid TFA/DCE (1 : 9) mixture was employed with microwave irradiation at 80 °C for 15 h, the conversion stopped when an unseparabale 1 : 1 mixture of 53 and the corresponding undecabromo analog was formed, as clearly revealed by 1 H NMR spectroscopy. [57] The extremely low solubility of compound 53 required the use of pyridine-d 5 as a solvent for full Scheme 8. Synthesis of dodecamethoxycentrohexaindane 52 from triptindanetrione 50.…”

“…By pursuing the retrosynthetic approach displayed in Scheme 6 ( 47 ⇐ 43 ), twelve methoxy groups were introduced by assembling the suitable veratrole‐derived building blocks along the propellane route (R=OMe) [52] . Alteratively, post‐functionalization of the parent hydrocarbon 5 was achieved using drastic halogenation conditions, which paved the way to the first congeners bearing twelve hydrocarbon substituents at the molecular periphery [57] …”

“…Under these conditions, the desired dodecabromo derivative 53 was formed as the exclusive product and isolated in excellent yield (>90 %). Interestingly, when the less acidid TFA/DCE (1 : 9) mixture was employed with microwave irradiation at 80 °C for 15 h, the conversion stopped when an unseparabale 1 : 1 mixture of 53 and the corresponding undecabromo analog was formed, as clearly revealed by 1 H NMR spectroscopy [57] . The extremely low solubility of compound 53 required the use of pyridine‐d 5 as a solvent for full characterization by NMR spectroscopy.…”