Showing papers by "Olivier Baudoin published in 2008"

Synthesis of Benzocyclobutenes by Palladium-Catalyzed C−H Activation of Methyl Groups: Method and Mechanistic Study

Abstract: An efficient catalytic system has been developed for the synthesis of benzocyclobutenes by C−H activation of methyl groups. The optimal conditions employed a combination of Pd(OAc)2 and PtBu3 as catalyst, K2CO3 as the base, and DMF as solvent. A variety of substituted BCB were obtained under these conditions with yields in the 44−92% range, including molecules that are hardly accessible by other methods. The reaction was found limited to substrates bearing a quaternary benzylic carbon, but benzocyclobutenes bearing a tertiary benzylic carbon could be obtained indirectly from diesters by decarboxylation. Reaction substrates bearing a small substituent para to bromine gave an unexpected regioisomer that likely arose from a 1,4-palladium migration process. The formation of this “abnormal” regioisomer could be suppressed by introducing a larger subsituent para to bromine. DFT(B3PW91) calculations on the reaction of 2-bromo-tert-butylbenzene with Pd(PtBu3) with different bases (acetate, bicarbonate, carbonate)...

Synthesis of anti-microtubule biaryls and preliminary evaluation as vascular-disrupting agents.

Abstract: A series of new dibenzoxepines were synthesized in a straightforward and efficient manner through diastereoselective biaryl Suzuki-Miyaura coupling and Br∅nsted-acid-mediated cyclodehydration as key steps. The vascular-disrupting potential of these molecules was evaluated with various in vitro assays: inhibition of microtubule assembly, antiproliferative activity against cancer cell lines and normal endothelial cells, modification of endothelial cell morphology, and disruption of endothelial cell cords. Two of these compounds showed promising activities in these assays, with profiles similar to that of the reference drug NAC and markedly different from that of colchicine. Altogether, these results show that dibenzoxepines represent promising new leads for the development of more selective vascular-disrupting agents.

Novel process for the preparation of functionalized benzocyclobutenes, and application to the synthesis of ivabradine and its salts of addition to a pharmaceutically acceptable acid

Abstract: Process for synthesizing compounds of formula (IV): ## STR1 ## in which R1, R2, R3 and R4 , identical or different, each represent a hydrogen atom, a linear or branched (C1-C6) alkyl group, a linear or branched (C1-C6) alkoxy group, a fluorine or chlorine atom, a protected amine group, a protected hydroxyl group, an alkoxycarbonyl group in which the alkoxy group is (C1-C6) linear or branched, a group CF3, or R1 = R4 = H and R2 and R3 form together with the carbon atoms which carry them a group 1 , 3-dioxolane, R5 represents a linear or branched, saturated or unsaturated (C1-C6) alkyl group, a linear or branched hydroxyalkyl (C1-C6) group whose hydroxyl function is protected, or a group CO2R7 in which R7 is a linear or branched (C1-C6) alkyl group, R6 represents a cyano group or a CO2R8 group in which R8 is a linear or branched (C1-C6) alkyl group. Application to the synthesis of ivabradine, its addition salts with a pharmaceutically acceptable acid and its hydrates.