Crystal structure of rac-4-Iodo-5 methoxy[2.2]metacylophane; a rare example of a halogenated metacyclophane with planar chirality

A racemic mixture of planar chiral 4-iodo-5-methoxy[2.2]metacylophane (2) was synthesized by the low-temperature directed ortho aryl metalation of 5-methoxy[2.2]metacyclophane (1) and subsequent in situ reaction with iodine. The crystal structure was determined by the single-crystal X-ray diffraction method at 100 K. The compound crystallized in an orthorhombic system and was characterized as: Pca21, a = 13.5690(2), b = 14.2212(2), c = 7.5004(1)Å, Z = 4, V = 1447.33(4)Å3. The crystal structure was solved by direct methods and refined by full-matrix least-squares on F2 to final values of R1 = 0.0281 and wR2 = 0.0733 for all 3021 independent reflection

Chiral auxiliary-mediated synthesis of planar chiral [2.2]metacyclophanes

The synthesis of planar chiral [2.2]metacyclophanes has been readily accomplished in a single synthetic step via the directed ortho metalation of a pro-chiral substituted metacyclophane. The use of (−)-menthyl chloroformate as a chiral auxiliary allows the introduction of the useful carbonyl functional group into the aryl ring, giving access to carboxy-substituted diastereomeric mixture of planar chiral [2.2]metacyclophanes. The separation of diastereoisomers has been easily accomplished by semipreparative HPLC, allowing the structural analysis of a single diastereoisomer by X-ray crystallography and NMR spectroscopy. The structural features of the planar chiral metacyclophanes and their high inversion barriers, determined at 473 K, encourage future investigations as chiral catalysts and ligands. This synthetic route complements our previously reported enantioselective synthesis avoiding the restrictive use of (−)-sparteine as the chiral inducer

Crystal structure of rac-4-Iodo-5 methoxy[2.2]metacylophane; a rare example of a halogenated metacyclophane with planar chirality

A racemic mixture of planar chiral 4-iodo-5-methoxy[2.2]metacylophane (2) was synthesized by the low-temperature directed ortho aryl metalation of 5-methoxy[2.2]metacyclophane (1) and subsequent in situ reaction with iodine. The crystal structure was determined by the single-crystal X-ray diffraction method at 100 K. The compound crystallized in an orthorhombic system and was characterized as: Pca21, a = 13.5690(2), b = 14.2212(2), c = 7.5004(1)Å, Z = 4, V = 1447.33(4)Å3. The crystal structure was solved by direct methods and refined by full-matrix least-squares on F2 to final values of R1 = 0.0281 and wR2 = 0.0733 for all 3021 independent reflection

Homo- and Hetero-oxidative Coupling of Benzyl Anions

The regioselective benzylic metalation of substituted toluenes using BuLi/KO-<i>t</i>-Bu/TMP­(H) (LiNK metalation conditions) with subsequent in situ oxidative C–C coupling has been developed for the facile generation of 1,2-diarylethanes. A range of oxidants can be used for the oxidative coupling step, with 1,2-dibromoethane proving optimal. Heterocouplings can be achieved starting from a mixture of two different toluenes with a bias toward cross coupling achievable by using a 2-fold excess of one toluene starting material. The utility of this approach is illustrated by the synthesis of several biologically active natural products. A distinct advantage is that the synthetic steps typically required to preactivate the coupling substrates are eliminated and no transition metal is required to facilitate the C–C bond formation

Light-Regulated NO Release as a Novel Strategy To Overcome Doxorubicin Multidrug Resistance

Nitric oxide (NO) release from a suitable NO photodonor (<b>NOP</b>) can be fine-tuned by visible light stimuli at doses that are not toxic to cells but that inhibit several efflux pumps; these are mainly responsible for the multidrug resistance of the anticancer agent doxorubicin (<b>DOX</b>). The strategy may thus increase <b>DOX</b> toxicity against resistant cancer cells. Moreover, a novel molecular hybrid covalently joining <b>DOX</b> and <b>NOP</b> showed similar increased toxicity toward resistant cancer cells and, in addition, lower cardiotoxicity than <b>DOX</b>. This opens new and underexplored approaches to overcoming the main therapeutic drawbacks of this chemotherapeutic based on light-controlled release of NO