Synthesis of Polysubstituted Ferrocenesulfoxides.

The purpose of the study is to design synthetic methodologies, especially directed deprotometalation using polar organometallic reagents, to access polysubstituted ferrocenesulfoxides. From enantiopure 2-substituted (SiMe3, PPh2) S-tert-butylferrocenesulfoxides, a third substituent was first introduced at the 5 position (SiMe3, I, D, C(OH)Ph2, Me, PPh2, CH2NMe2, F) and removal of the trimethylsilyl group then afforded 2-substituted ferrocenesulfoxides unreachable otherwise. Attempts to apply the "halogen dance" reaction to the ferrocenesulfoxide series led to unexpected results although rationalized in light of calculated pKa values. Further functionalizations were also possible. Thus, new enantiopure, planar chiral di- and trisubstituted ferrocenes have been obtained, in addition to several original 2-substituted, 2,3- and 2,5-disubstituted, 2,3,5-trisubstituted and even 2,3,4,5-tetrasubstituted ferrocenesulfoxides, also enantiopure.

Dehalogenative or Deprotonative? The Preparation Pathway to the Organometallic Monomer for Transition-Metal-Catalyzed Catalyst-Transfer-Type Polymerization of Thiophene Derivatives.

Due to a wide range of applications in electronic materials, polythiophenes attract considerable attention in organic and polymer syntheses as well as in materials science. For the purpose of developing the practical synthetic protocol, this review focuses on the deprotonative pathway in the preparation of thiophene organometallic monomer, which was shown to be effective employing 2-halo-3-substituted thiophene as a monomer precursor. The thus metallated thiophene monomer was shown to undergo polymerization by nickel(II) complex catalysis, with which highly regioregular head-to-tail (HT)-type polythiophenes were obtained with controlled molecular weight and molecular weight distribution. Several polythiophene derivatives with modified thiophene-ring and side-chain structures were shown to be designed in order to achieve the designed functionality as materials.

Deprotometalation-iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues.

1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N-arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base. From 2-phenyl-1,2,3-triazoles, and in particular from 2-(4-trifluoromethoxy)phenyl-1,2,3-triazole, reactions at the 4 position of the triazolyl, but also ortho to the triazolyl on the phenyl group, were observed. The results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method. 4-Iodo-2-phenyl-1,2,3-triazole and 4-iodo-2-(2-iodophenyl)-1,2,3-triazole were next involved in Suzuki coupling reactions to furnish the corresponding 4-arylated and 4,2'-diarylated derivatives. When evaluated for biological activities, the latter (which are resveratrol analogues) showed moderate antibacterial activity and promising antiproliferative effect against MDA-MB-231 cell line.

Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells.

Benzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium-zinc combination prepared from ZnCl2·TMEDA (TMEDA=N,N,N',N'-tetramethylethylenediamine, 1equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3equiv). Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81%, 82%, 67% and 42% yields, respectively. These yields are higher (10% more) than those obtained using ZnCl2·TMEDA (0.5equiv) and LiTMP (1.5equiv), except in the case of benzoxazole (10% less). The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. Using benzotriazole also led to N-arylation products, but in lower 34%, 39%, 36% and 6% yields, respectively. A further study with this azole evidenced the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields. Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10(-5)M.