Malose J. Mphahlele

Molecular iodine-mediated cyclization of tethered heteroatom-containing alkenyl or alkynyl systems.

Molecular iodine has established itself as a readily available and easy-to-handle electrophilic and oxidizing reagent used in various organic transformations. In this review attention is focused on the use of molecular iodine in promoting cyclization (iodocyclization and cyclodehydroiodination) of tethered heteroatom-containing alkenyl or alkynyl systems.

Molecular Iodine—An Expedient Reagent for Oxidative Aromatization Reactions of α,β-Unsaturated Cyclic Compounds

Prompted by the scant attention paid by published literature reviews to the applications of molecular iodine in oxidative aromatization reactions, we decided to review methods developed to-date involving iodine as an oxidant to promote aromatization of α,β-unsaturated cyclic compounds.

Synthesis and Photophysical Property Studies of the 2,6,8-Triaryl-4-(phenylethynyl)quinazolines

The 2-aryl-6,8-dibromo-4-chloroquinazolines derived from the 2-aryl-6,8-dibromoquinazolin-4(3H)-ones were subjected to the Sonogashira cross-coupling with terminal acetylenes at room temperature to afford novel 2-aryl-6,8-dibromo-4-(alkynyl)quinazoline derivatives. Further transformation of the 2-aryl-6,8-dibromo-4-(phenylethynyl)quinazolines via Suzuki-Miyaura cross-coupling with arylboronic acids occurred without selectivity to afford the corresponding 2,6,8-triaryl-4-(phenylethynyl)quinazolines. The absorption and emission properties of these polysubstituted quinazolines were also determined.

Advances in Metal-Catalyzed Cross-Coupling Reactions of Halogenated Quinazolinones and Their Quinazoline Derivatives

Halogenated quinazolinones and quinazolines are versatile synthetic intermediates for the metal-catalyzed carbon–carbon bond formation reactions such as the Kumada, Stille, Negishi, Sonogashira, Suzuki-Miyaura and Heck cross-coupling reactions or carbon-heteroatom bond formation via the Buchwald-Hartwig cross-coupling to yield novel polysubstituted derivatives. This review presents an overview of the application of these methods on halogenated quinazolin-4-ones and their quinazolines to generate novel polysubstituted derivatives.

2-aryl-4-chloro-3-iodoquinolines as substrates for the synthesis of 2,3-diaryl-4-methoxyquinolines

Sequential functionalisation of 2-aryl-4-chloro-3-iodoquinolines via palladium–catalysed cross-coupling with phenylboronic acid followed by displacement of the 4-chloro atom from the resulting 2,3-diaryl-4-chloroquinolines with methoxide ion yielded 2,3-diaryl-4-methoxyquinolines. The latter were also prepared via Suzuki–Miyaura cross-coupling of 2-aryl-3-iodo-4-methoxyquinolines with phenylboronic acid. Demethylation of the methoxy compounds (BBr3) gave the 2,3-diaryl-4(1H)-quinolinones.

One-Pot Synthesis of 2,3,4-Triarylquinolines via Suzuki- Miyaura Cross-Coupling of 2-Aryl-4-chloro-3-iodoquinolines with Arylboronic Acids

Palladium–catalyzed Suzuki cross-coupling of 2-aryl-4-chloro-3-iodoquinolines with excess arylboronic acids (2.5 equiv.) in the presence of tricyclohexylphosphine afforded the 2,3,4-triarylquinolines in one-pot operation. The incipient 2,3-diaryl-4-chloroquinolines were also prepared and transformed to the primary 4-amino-2,3-diarylquinolines and 2,3-diarylquinolin-4(1H)-ones.

In vitro cytotoxicity of novel 2,5,7-tricarbo-substituted indoles derived from 2-amino-5-bromo-3-iodoacetophenone

A series of novel 2,5,7-tricarbo-substituted indoles were prepared via sequential Sonogashira and Suzuki-Miyaura cross-coupling of 2-amino-5-bromo-3-iodoacetophenone with terminal acetylenes and aryl/styrylboronic acids followed by palladium chloride-mediated heteroannulation of the incipient 5-aryl/styryl-substituted 2-amino-3-(arylalkynyl)acetophenones. These polycarbo-substituted indole derivatives were evaluated for potential in vitro antiproliferative activity against the human breast adenocarcinoma (MCF-7) and human cervical cancer (HeLa) cell lines. Compounds 6f, 6i, 6k, 6m and 6n were found to exhibit significant cytotoxicity and selectivity against the HeLa cells. Compounds 6i and 6m were chosen as representative examples to evaluate their pro-apoptotic efficacy against the HeLa cell line. The compounds induced apoptosis through cell membrane alteration and DNA fragmentation caspase-dependent pathways.

Synthesis and Photophysical Properties of Polycarbo-Substituted Quinazolines Derived from the 2-Aryl-4-chloro-6-iodoquinazolines

The reactivity of the 2-aryl-4-chloro-6-iodoquinazolines towards palladium catalyzed sequential (Sonogashira/Suzuki-Miyaura) and one-pot two-step cross-coupling (bis-Sonogashira, and successive Sonogashira/Stille) reactions to afford novel unsymmetrical polycarbo-substituted quinazolines has been evaluated. In contrast to the chloro-bromo substituted quinazolines in which selectivity has been previously found to generally favor substitution at the more activated C(4)-Cl bond over the weaker Csp2-Br bond, substitution in the case of the chloro-iodo derivatives favors cross-coupling through the intrinsically more reactive Csp2-I bond. The electronic absorption and emission properties of the prepared 2,3-diaryl-6-(phenylethynyl)quinazolines were studied in solvents of different polarity (dichloromethane, toluene, DMF, methanol) and CH2Cl2-TFA mixture using UV-Vis and emission spectroscopic techniques complemented with density functional theory method to establish the effect of substituents on intramolecular charge transfer properties.

Synthesis and Photophysical Properties of 2-Aryl-6,8-bis(arylethenyl)-4-methoxyquinolines

Iodine-methanol mediated oxidative-aromatization of 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones afforded the corresponding 2-aryl-6,8-dibromo-4-methoxy-quinolines in high yield and purity. The isomeric 1-(2-amino-3,5-dibromophenyl)-3-aryl-2-propen-1-ones reacted with iodine in methanol afford in a single pot operation the corresponding 2-aryl-6,8-dibromo-4-methoxyquinoline (major) and 2-aryl-6,8-dibromoquinolin-4(1H)-one (minor) products that were separated in sequence by column chromatography on silica gel. Suzuki-Miyaura cross-coupling of the 6,8-dibromo-4-methoxyquinoline derivatives with excess arylvinylboronic acids afforded the corresponding 2-aryl-6,8-bis(2-arylethenyl)-4-methoxyquinolines. The absorption and fluorescence properties of these compounds were also determined.

Novel Polycarbo-Substituted Imidazo[1,2-c]quinazolines: Synthesis and Cytotoxicity Study

Amination of the 2-aryl-6-bromo-4-chloro-8-iodoquinazolines with 2-aminoethanol followed by acid-promoted cyclodehydration of the incipient 2-((6,8-dihalo-2-phenylquinazolin-4-yl)amino)ethanols afforded the corresponding novel 5-aryl-9-bromo-7-iodo-2,3-dihydro-2H-imidazo[1,2-c]quinazolines. The latter were, in turn, subjected to sequential (Sonogashira and Suzuki-Miyaura) and one-pot two-step (Sonogashira/Stille) cross-coupling reactions to afford diversely functionalized polycarbo-substituted 2H-imidazo[1,2-c]quinazolines. The imidazoquinazolines were screened for in vitro cytotoxicity against human breast adenocarcinoma (MCF-7) cells and human cervical cancer (HeLa) cells.