Diels–Alder Reactions of 9‑Ferrocenyl- and 9,10-Diferrocenylanthracene: Steric Control of 9,10- versus 1,4-Cycloaddition

Cycloadditions of benzynes, <i>N</i>-methyl- or <i>N</i>-phenylmaleimide, dimethyl acetylenedicarboxylate, and benzoquinone to 9-ferrocenylanthracene (<b>1</b>) and 9,10-diferrocenylanthracene (<b>2</b>) are described. Benzyne and 3-fluorobenzyne add to <b>1</b> and <b>2</b> to form the corresponding 9-ferrocenyl- or 9,10-diferrocenyltriptycenes; in contrast, bulkier benzynes such as 3-trifluoromethylbenzyne preferentially add to <b>2</b> across C₁ and C₄ to form 6,11-diferrocenyl-5,12-etheno-5,12-dihydrotetracenes. The maleimides undergo Diels–Alder reactions with <b>1</b> to form the 9-ferrocenylbarrelenes <b>10</b> and <b>11</b>, but cycloaddition to <b>2</b> occurs not only across C₉ and C₁₀ to form the barrelene <b>13</b> but also across C₁ and C₄ to yield ethenoanthracenes as both endo and exo adducts, <b>14</b> and <b>15</b>, respectively. Likewise, DMAD forms 11,12-dicarbomethoxy-9-ferrocenylbarrelene (<b>16</b>) with <b>1</b> but reacts with <b>2</b> by addition across C₁ and C₄ to form <b>17</b>. Hydrolysis of <b>16</b> cleaves only the ester distant from the ferrocenyl group. Treatment of the Diels–Alder adduct <b>20</b> of 9-ferrocenylanthracene (<b>1</b>) and benzoquinone with base and RX (R = Me, Et, CH₂OMe, CH₂CO₂Me) yields the corresponding 1,4-dialkoxy-9-ferrocenyltriptycenes <b>22</b>–<b>25</b>. The factors influencing the regiochemistry of the cycloadditions are discussed, and several examples of each reaction type have been characterized by X-ray crystallography

High and Low Rotational Barriers in Metal Tricarbonyl Complexes of 2- and 3‑Indenyl Anthracenes and Triptycenes: Rational Design of Molecular Brakes

Syntheses and X-ray crystal structures are reported for a series of M­(CO)₃ derivatives (M = Cr, Re) of phenyl and also 2- and 3-indenyl anthracenes and triptycenes. In each case, the rotational barrier about the bond linking the two organic fragments was evaluated both experimentally by VT or 2D-EXSY NMR and by calculation at the DFT level. Attachment of the metal tripod to the indenyl moiety in an η⁶ fashion does not markedly change the barrier relative to that for the free ligand but lowers the symmetry so as to facilitate its direct measurement. Interestingly, an η⁶ → η⁵ haptotropic shift of the Cr­(CO)₃ moiety in 9-indenylanthracenes led to a somewhat lowered barrier, probably attributable to an increase in the ground state energy rather than to decreased steric interactions in the transition state. In contrast, in indenyltriptycenes η⁶ → η⁵ migration of the M­(CO)₃ unit along the indenyl skeleton and closer to a paddlewheel leads to a very significant increase in the rotational barrier. These effects can be rationalized in terms of angular steric strain and multiple interactions in the ground state and in the transition state. The results not only provide semiquantitative data on the steric effects of η⁶-phenyl and η⁶- or η⁵-indenyl M­(CO)₃ fragments but are also discussed with relevance to their role in organometallic molecular brakes

A New Series of Succinimido-ferrociphenols and Related Heterocyclic Species Induce Strong Antiproliferative Effects, Especially against Ovarian Cancer Cells Resistant to Cisplatin

Ferrociphenols are known to display anticancer properties by original mechanisms dependent on redox properties and generation of active metabolites such as quinone methides. Recent studies have highlighted the positive impact of oxidative stress on chemosensitivity and prognosis of ovarian cancer patients. Ovarian adenocarcinomas are shown to be an excellent model for defining the impact of selected ferrociphenols as new therapeutic drugs for such cancers. This work describes the syntheses and preliminary mechanistic research of unprecedented multitargeting heterocyclic ferrociphenols bearing either a succinimidyl or phthalimidyl group that show exceptional antiproliferative behavior against epithelial ovarian cancer cells resistant to cisplatin. Owing to the failure of the present pharmaceutical options, such as carboplatin a metallodrug based on Pt coordination chemistry, these species may help to overcome the problem of lethal resistance. Currently, ferrociphenolic entities generally operate via apoptotic and senescence pathways. We present here our first results in this new cyclic-imide series