2020-01- DABCO‐promoted diaryl thioether formation by metal‐catalyzed coupling of sodium sulfinates and aryl iodides
Liu, Y.; Lam, L. Y.; Blanchard, N.; Ma, C. V. Adv. Synth. Catal. 2020, 362, 2326-2331.
A scalable catalytic synthesis method using commodity chemicals for constructing diaryl thioethers directly from sodium arylsulfinates and iodoarenes is reported in this study. In the presence of CuO or other copper salts such as Cu(OAc)2 as well as palladium catalysts, DABCO demonstrated to be essential to promote this transformation. Various iodoarenes and aryl sulfinates were examined and demonstrated the viability of this method. The mechanistic study showed that radical reactions occurred, while DABCO N‐oxide radical can be observed by mass spectrometry. A plausible catalytic mechanism involving DABCO is also discussed, suggesting synergistic reduction of sulfinate by Cu(II) and DABCO is the key step of this coupling reaction.
2020-02- Optimized Synthesis of 7-Azaindazole by a Diels–Alder Cascade and Associated Process Safety
Brach, N.; Le Fouler, V.; Bizet, V.; Lanz, M.; Gallou, F.; Bailly, C.; Hoehn, P.; Parmentier, M.; Blanchard, N. Org. Process. Res. Dev. 2020, 24, 776-786.
Although pyrimidines are not among the most reactive partners in intramolecular inverse-electron-demand [4πs + 2πs] reactions with alkynes, they can be activated under mild and practical conditions, leading to fused nitrogen-containing heterocycles. We report an optimized synthesis of a 5-iodo-7-azaindazole by a one-pot Diels–Alder cascade that starts from a pyrimidine substituted at the 2-position by an (alkynyl)hydrazone. The safety of the process and the environmental impact were thoroughly evaluated. Eventually, a selection of cross-coupling reactions were studied and found to allow the introduction of carbon- and nitrogen-based nucleophiles at the 5-position in good to excellent yields.
2020-03- Ligand-Controlled Regiodivergent Palladium-Catalyzed Hydrogermylation of Ynamides
Debrauwer, V.; Turlik, A.; Rummler, L.; Prescimone, A.; Blanchard, N.; Houk, K. N.; Bizet, V. J. Am. Chem. Soc. 2020, 142, 11153-11164.
Ynamides are fascinating small molecules with complementary reactivities under radical, ionic and metal-catalyzed conditions. We report herein synthetic and DFT investigations of palladium-catalyzed ligand-controlled regiodivergent hydrometallation reactions of ynamides. Germylated and stannylated enamides are obtained with excellent α,E- or β,E-selectivities and a broad functional group tolerance. Such a regiodivergent palladium-catalyzed process is unique in ynamide chemistry and allows the elaboration of metallated-enamides that are very useful building blocks for cross-coupling reactions or heterocyclic chemistry. DFT calculations fully support the experimental data and demonstrate the crucial roles of the trans-geometry of the [H-Pd(L)-Ge] complex, as well as of the steric requirements of the phosphine ligand. In addition, these calculations support the prevalence of a hydro-palladation pathway over a metal-palladation of the π system of the ynamide. Highlighted in: Actualités de l’INC CNRS, 9 octobre 2020 (link).
Burton, D. J.; Wang, Y.; Bizet, V.; Cahard, D. e-EROS Encyclopedia of Reagents for Organic Synthesis. Wiley,2020, DOI:10.1002/047084289X.rn00413.pub2.
Compounds featuring the SF5 motif are noted for their chemical properties that include high chemical and thermal stability, hydrolytic stability, high lipophilicity and hydrophobicity, low polarizability, high density, low boiling point, and low surface tension. Prior to 2002, the production of pentafluorosulfanyl compounds with the aid of SF5Cl relied on the use of excessive temperatures, high-pressure autoclaves, photochemical procedures, and hazardous reactants, leading to targeted molecules in low or variable yields. Furthermore, due to the nature of the processes involved, significant generation of toxic side products was observed. The use of triethylborane (Et3B) as a catalytic initiator for the free radical chain addition of SF5Cl to alkenes and alkynes provided an improvement for the synthesis of SF5-containing structures.
Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU) disease, is unique amongst human pathogens in its capacity to produce a lipid toxin called mycolactone. While previous studies have demonstrated that bacterially-released mycolactone diffuses beyond infection foci, the spatiotemporal distribution of mycolactone remained largely unknown. Here, we used the zebrafish model to provide the first global kinetic analysis of mycolactone’s diffusion in vivo, and multicellular co-culture systems to address the critical question of the toxin’s access to the brain.
