Atroposelective Synthesis of Isoriccardin C through a C−H Activated Heck Type Macrocyclization

Macrocyclization is typically the key step in syntheses of cyclophane‐type natural products. Considering compounds with axially chiral biaryl moieties, the control of atroposelectivity is essential for biological activity and is synthetically challenging. Herein we report on atroposelective macrocyclization involving an oxidative Heck type process and enabling the first atropo‐enantiopure synthesis of isoriccardin C. A chiral sulfinyl auxiliary in the ortho‐position of a biaryl axis (still flexible) was used to induce a C−H activated atropodiastereoselective oxidative Heck coupling (>98 % de). The traceless character of the sulfinyl auxiliary enables the introduction of a hydroxy group to give the target molecule with >98 % ee as well

[7,0]-metacyclophanes from biaryl coupling/macrocyclisation

The biaryl structural motif is a predominant feature in many pharmaceutically relevant and biologically active compounds. As a result, for over a century organic chemists have sought to develop new and more efficient aryl-aryl bond-forming methods (1). Cyclophanic natural products comprise an intriguing class of structurally diverse compounds. As inherent for all cyclic compounds regardless of their origin, macrocyclization is naturally the most decisive step, which defines the overall efficiency of the synthetic pathway. Especially in small cyclophanic molecules, this key step constitutes an even greater challenge. Due to the strain imparted by the macrocyclic system, free rotation of the benzene ring(s) is often restricted depending on both the constitution of the tether and the aromatic portions (2). Among cyclophanic natural products, the diarylheptanoids are a structurally sub-class with their scaffold consisting of two benzene rings tethered by an oxygenated aliphatic heptyl chain. In this work we reported different metal catalysed approaches to obtain the biaryl motif of myricanol, a natural [7,0]-metacyclophane with very important and recently discovered biological activities (3),(4),(5),(6). (Figure 1) Figure 1 The desired product 1could be obtained from the functionalized linear diarylheptanoid 2 by Suzuki domino process (macrocyclisation by linkage of aryl moieties) or could be synthesized from ring closing metathesis of product 3 which derived from a biaryl coupling of fragments 4 and 5. (1) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107 (1), 174–238. (2) Gulder, T.; Baran, P. S. Nat. Prod. Rep. 2012, 29 (8), 899-934. (3) Jones, J. R.; Lebar, M. D.; Jinwal, U. K.; Abisambra, J. F.; Koren, J.; Blair, L.; O’Leary, J. C.; Davey, Z.; Trotter, J.; Johnson, A. G.; Weeber, E.; Eckman, C. B.; Baker, B. J.; Dickey, C. A. J. Nat. Prod. 2011, 74 (1), 38–44. (4) Martin, M. D.; Calcul, L.; Smith, C.; Jinwal, U. K.; Fontaine, S. N.; Darling, A.; Seeley, K.; Wojtas, L.; Narayan, M.; Gestwicki, J. E.; Smith, G. R.; Reitz, A. B.; Baker, B. J.; Dickey, C. A. ACS Chem. Biol. 2015, 10 (4), 1099–1109. (5) Dai, G. H.; Meng, G. M.; Tong, Y. L.; Chen, X.; Ren, Z. M.; Wang, K.; Yang, F. Phytomedicine 2014, 21 (11), 1490–1496. (6) Dai, G.; Tong, Y.; Chen, X.; Ren, Z.; Ying, X.; Yang, F.; Chai, K. Int. J. Mol. Sci. 2015, 16 (2), 2717–2731

Joint ITC and DFT Study of the Affinity of Some Lewis Bases to HIFP in Solution

HFIP, i.e. 1,1,1,3,3,3-hexafluoropropan-2-ol, was found to be an exceptional medium,[1] either as solvent or co-solvent, that allows many reactions to occur.[2-5] However, the exact role and mode of action of HFIP in various chemical transformations still remains elusive. Despite many reports dealing with water/HFIP complexes, little has been published on other molecular complexes of HFIP as well as on thermochemistry of the formation of such complexes.[6] Within this study the affinity of a series of eight different Lewis bases (3 sulfoxides, 3 Nsp2 pyridine derivatives, 1 aromatic amine, 1 cyclic aliphatic ether) to HFIP (as Lewis acid) is investigated experimentally by Isothermal Titration Calorimetry (ITC) and theoretically using static DFT-D calculations. Measured ITC association enthalpy values ΔHaITC spanned -9.3 kcal/mol - -14 kcal/mol. Computations including a PCM implicit solvation model produced similar exothermicity of association of all studied systems - ΔHa values ranging -8.5 – -12.7 kcal/mol. In general, most of interaction energy is due to the hydrogen bonding and not due to formation of significantly strong halogen bonds. An additional set of calculations combining implicit and explicit solvation by chlorobenzene of the reactants, pointed out the relatively low interference of the solvent with the HFIPbase complexation, which main effect is to slightly enhance the Gibbs energy of the HFIP-Lewis base association. It is speculated that the interactions of bulk HFIP with Lewis bases therefore may significantly intervene in catalytic processes not only via the dynamic miscrostructuration of the medium but also more explicitly by affecting bonds’ polarization at the Lewis bases

Triazolo[1,5-a]pyridyl phosphines reflecting the influence of phosphorus lone pair orientation on spectroscopic properties

A series of new triazolopyridine-based phosphines has been prepared. These compounds revealed unexpected spectroscopic patterns. In particular, the NMR spectra are highly dependent on the relative conformational preference of the phosphine substituent at C7. Here, we report on their complete NMR analysis, X-ray structures and DFT calculations that confirm the particular arrangement of the phosphorus lone pair orbital related to the substituent pattern of the chosen phosphine. © 2011 The Royal Society of Chemistry.Peer Reviewe

Supplementary data for the article: Milovanović, M. R.; Dherbassy, Q.; Wencel‐Delord, J.; Colobert, F.; Zarić, S. D.; Đukić, J.-P. The Affinity of Some Lewis Bases for Hexafluoroisopropanol as a Reference Lewis Acid: An ITC/DFT Study. ChemPhysChem 2020, 21 (18), 2136–2142. https://doi.org/10.1002/cphc.202000560.

Supplementary material for: [https://doi.org/10.1002/cphc.202000560]Related to published version: [https://cherry.chem.bg.ac.rs/handle/123456789/4337]Related to accepted version: [https://cherry.chem.bg.ac.rs/handle/123456789/4339

El rechazo entre iguales: una visión general

III Jornadas Internacionales del Grupo GREIHablar de aceptación y rechazo entre iguales es un tema de gran relevancia en nuestro contexto social actual. Este hecho es consecuencia de la importancia que tiene la atracción interpersonal como índice de adaptación socioemocional, ya que la realidad evidencia que una buena aceptación en el grupo de compañeros y compañeras favorece una buena adaptación y bienestar socioemocional, mientras que niveles bajos de aceptación social son factores de riesgo y de problemática en el tema de interacción socialAcceptance and rejection between peers have become a relevant issue in our current social context. This is a consequence of the importance that interpersonal attraction is bestowed as a socio-emotional adaptation system. Indeed, as reality evidences, strong acceptance levels among peers foster not only better adaptation within the group but also better levels of socio-emotional well-being. However, low social acceptance levels stand as problematic risk factors regarding social interaction