Abstract The thermal 4π-electrocyclic ring-opening reaction of fused-cyclobutenes formally generates cis,trans-cycloalka-1,3-dienes, highly strained intermediates that are difficult to observe directly. Although these species have been implicated in various stereospecific transformations, their dynamic behavior has remained largely unexplored. Herein, we report kinetic analyses of the 4π-electrocyclic reaction and apparent racemization of a series of bicyclo[5.2.0]nonenes. The rates of ring-opening, ring-closing, and racemization were found to be strongly influenced by substituents and solvent polarity. Isolation and X-ray crystallographic characterization of a cis,trans-cyclonona-1,3-diene derivative provided direct structural evidence for the ring-opened intermediate. Kinetic analysis revealed that apparent racemization is closely coupled with electrocyclic ring-opening, providing a mechanistic basis for the rapid loss of stereochemical information observed in trapping reactions.
Abstract The direct addition of C–H bonds across allenes represents an attractive strategy for the construction of allylic frameworks, but controlling the selectivity remains a major challenge. In this Synpacts article, we summarize the development of an Ir(I) catalytic system featuring a perfluorinated bisphosphine ligand, dFppe, which directs the reaction toward branched allylic products with high chemo- and regioselectivity. The method is applicable to several classes of C–H partners, including N-substituted pyrrole carboxamides, furans, and β-unsubstituted acrylamides, and accommodates both mono- and 1,1-disubstituted allenes. As a result, densely substituted products bearing tertiary or all-carbon quaternary centers can be accessed efficiently. Preliminary asymmetric studies with chiral ligands show promising levels of enantioinduction with a pentafluoroaryl-containing bisphosphinite, while DFT calculations indicate that noncovalent interactions involving the fluorinated ligand play a key role in stabilizing the branched-selective reaction pathways.
Microwave irradiation often accelerates asymmetric catalytic reactions at the expense of stereoselectivity because the rate enhancement is primarily derived from thermal effects. Herein, we report an iridium-catalyzed asymmetric oxidative lactonization of meso-diols that exhibits significant rate enhancement without erosion of enantioselectivity. These observations are consistent with microwave-associated acceleration beyond conventional thermal effects. One possible explanation is facilitation of formation of a reactive substrate conformation during the initial oxidation step leading to the hydroxyaldehyde/lactol manifold. Mechanistic studies also revealed an unexpected catalytic asymmetric dehydrogenative pathway under degassed conditions.
An electrochemical P=N bond-forming reaction is demonstrated, which provides a practical and environmentally friendly method to access N-sulfonyl iminophosphoranes. This protocol exhibits broad substrate scope, good functional group tolerance, and good atom economy. Mechanistic studies, supported by cyclic voltammetry analysis, suggest that the reaction might begin with the anodic oxidation of trisubstituted phosphines.
Abstract Molecular conformational transitions are central to supramolecular self-assembly but remain difficult to elucidate in complex biological systems. Herein, we report a structurally well-defined small-molecule model, an iodinated furan-2,5-dicarboxanilide, that undergoes pronounced conformational switching upon assembly. In solution, it adopts a thermodynamically favored V-shaped conformation stabilized by two intramolecular N–H···O hydrogen bonds, as supported by DFT calculations and NOESY analysis. In contrast, single-crystal X-ray diffraction reveals an unexpected extended conformation in the solid state, in which all interaction sites are exposed. Hirshfeld surface analysis shows that H···I contacts (17.5%), rather than classical I···I halogen bonds (2.7%), dominate the intermolecular interactions and cooperate with N–H···O hydrogen bonds to drive dense three-dimensional packing. The total intermolecular interaction energy (58.7 kcal mol−1) outweighs the conformational energy penalty (8.37 kcal mol−1), demonstrating that crystal packing forces override intrinsic conformational preferences. This work provides a mechanistic paradigm for assembly-controlled conformational switching driven by weak but collective intermolecular interactions.
