Hydrosulfonylation of Unactivated Alkenes and Alkynes by Halogen-Atom Transfer (XAT) Cleavage of S^VI–F Bond

A photochemical halogen-atom transfer (XAT) method for generating sulfonyl radicals from aryl sulfonyl fluorides has been developed. It allows the hydrosulfonylation of unactivated alkenes, which was challenging to achieve through our previous single-electron transfer route. This reaction has excellent functional group tolerance and substrate scope under mild conditions

Rhodium-Catalyzed Enantioselective N‑Allylation of Sulfoximines

The N-functionalization of free sulfoximines is an important approach to modifying their chemical and biological properties for downstream applications. Here, we report a rhodium-catalyzed N-allylation of free sulfoximines (NH) with allenes under mild conditions. The redox-neutral and base-free process enables chemo- and enantioselective γ-hydroamination of allenes and gem-difluoroallenes. Synthetic applications of sulfoximine products obtained thereof have been demonstrated

From Olefination to Alkylation: In-Situ Halogenation of Julia–Kocienski Intermediates Leading to Formal Nucleophilic Iodo- and Bromodifluoromethylation of Carbonyl Compounds

Iodo- and bromodifluoromethylated compounds are important synthetic intermediates and halogen-bond acceptors. However, direct introduction of −CF₂I and −CF₂Br groups through nucleophilic addition is particularly challenging because of the high tendency of decomposition of CF₂Br^– and CF₂I^– to difluorocarbene. In this work, we have developed a formal nucleophilic iodo- and bromodifluoromethylation for carbonyl compounds. The key strategy of the method is the halogenation of in situ-generated sulfinate intermediates from the Julia–Kocienski reaction to change the reaction pathway from the traditional olefination to alkylation. Interesting halogen−π interactions between the halocarbon and aromatic donors were observed in the crystal structures of the products. The method could also be extended to the introduction of other fluorinated groups, such as −CFClBr, −CFClI, −CFBr₂, and −CFMeI, which opens up new avenues for the synthesis of a wide range of useful fluorinated products

Protonated Arginine and Protonated Lysine: Hydration and Its Effect on the Stability of Salt-Bridge Structures

Using a mass spectrometer equipped with a drift cell, water binding energies of protonated arginine (ArgH+) and protonated lysine (LysH+) were determined in equilibrium experiments and supplementary calculations at the B3LYP/6-311++G** level of theory. The binding energy of the first water molecule was measured to be 10.3 and 10.9 kcal/mol for ArgH+ and LysH+, respectively. Water binding energies decrease with increasing degree of hydration reaching values of 6−7 kcal/mol for the fourth and fifth water molecule. Theory reproduces this trend of decreasing binding energies correctly and theoretical water binding energies agree with experiment quantitatively within 2 kcal/mol. Lowest-energy theoretical structures of ArgH+ and LysH+ are characterized by protonated side chains and neutral α-amino and carboxyl groups which form intramolecular hydrogen bonds to the ionic group (charge solvation or CS structures). The salt bridge (SB) structures with two cationic groups (side chain and α-amine) and one anionic group (carboxyl) are 13.1 and 9.3 kcal/mol higher in energy for ArgH+ and LysH+, respectively. Theory indicated that the first water molecule binds to the ionic group of the CS structures of ArgH+ and LysH+. With increasing degree of hydration intramolecular interactions are replaced one by one with water bridges with water inserted into the intramolecular hydrogen bonds. Whereas the global minima of ArgH+·(H2O)n and LysH+·(H2O)n, n CS structures, 7-fold hydrated CS and SB structures, ArgH+·(H2O)7 and LysH+·(H2O)7, are nearly isoenergetic (within <1 kcal/mol)

From Olefination to Alkylation: In-Situ Halogenation of Julia–Kocienski Intermediates Leading to Formal Nucleophilic Iodo- and Bromodifluoromethylation of Carbonyl Compounds

Iodo- and bromodifluoromethylated compounds are important synthetic intermediates and halogen-bond acceptors. However, direct introduction of −CF₂I and −CF₂Br groups through nucleophilic addition is particularly challenging because of the high tendency of decomposition of CF₂Br^– and CF₂I^– to difluorocarbene. In this work, we have developed a formal nucleophilic iodo- and bromodifluoromethylation for carbonyl compounds. The key strategy of the method is the halogenation of in situ-generated sulfinate intermediates from the Julia–Kocienski reaction to change the reaction pathway from the traditional olefination to alkylation. Interesting halogen−π interactions between the halocarbon and aromatic donors were observed in the crystal structures of the products. The method could also be extended to the introduction of other fluorinated groups, such as −CFClBr, −CFClI, −CFBr₂, and −CFMeI, which opens up new avenues for the synthesis of a wide range of useful fluorinated products

Hydration of Protonated Aromatic Amino Acids: Phenylalanine, Tryptophan, and Tyrosine

The first steps of hydration of the protonated aromatic amino acids phenylalanine, tryptophan, and tyrosine were studied experimentally employing a mass spectrometer equipped with a drift cell to examine the sequential addition of individual water molecules in equilibrium experiments and theoretically by a combination of molecular mechanics and electronic structure calculations (B3LYP/6-311++G**) on the three amino acid systems including up to five water molecules. It is found that both the ammonium and carboxyl groups offer good water binding sites with binding energies of the order of 13 kcal/mol for the first water molecule. Subsequent water molecules bind less strongly, in the range of 7−11 kcal/mol for the second through fifth water molecules. The ammonium group is able to host up to three water molecules and the carboxyl group one water molecule before additional water molecules bind either to the amino acid side chain as in tyrosine or to already-bound water in a second solvation shell around the ammonium group. Reasons for the surprisingly high water affinity of the neutral carboxyl group, comparable to that of the charge-carrying ammonium group, are found to be high intrinsic hydrophilicity, favorable charge−dipole alignment, and  for the case of multiply hydrated species  favorable dipole−dipole interaction among water molecules and the lack of alternative fully exposed hydration sites

From Olefination to Alkylation: In-Situ Halogenation of Julia–Kocienski Intermediates Leading to Formal Nucleophilic Iodo- and Bromodifluoromethylation of Carbonyl Compounds

Iodo- and bromodifluoromethylated compounds are important synthetic intermediates and halogen-bond acceptors. However, direct introduction of −CF₂I and −CF₂Br groups through nucleophilic addition is particularly challenging because of the high tendency of decomposition of CF₂Br^– and CF₂I^– to difluorocarbene. In this work, we have developed a formal nucleophilic iodo- and bromodifluoromethylation for carbonyl compounds. The key strategy of the method is the halogenation of in situ-generated sulfinate intermediates from the Julia–Kocienski reaction to change the reaction pathway from the traditional olefination to alkylation. Interesting halogen−π interactions between the halocarbon and aromatic donors were observed in the crystal structures of the products. The method could also be extended to the introduction of other fluorinated groups, such as −CFClBr, −CFClI, −CFBr₂, and −CFMeI, which opens up new avenues for the synthesis of a wide range of useful fluorinated products

From Olefination to Alkylation: In-Situ Halogenation of Julia–Kocienski Intermediates Leading to Formal Nucleophilic Iodo- and Bromodifluoromethylation of Carbonyl Compounds

Iodo- and bromodifluoromethylated compounds are important synthetic intermediates and halogen-bond acceptors. However, direct introduction of −CF₂I and −CF₂Br groups through nucleophilic addition is particularly challenging because of the high tendency of decomposition of CF₂Br^– and CF₂I^– to difluorocarbene. In this work, we have developed a formal nucleophilic iodo- and bromodifluoromethylation for carbonyl compounds. The key strategy of the method is the halogenation of in situ-generated sulfinate intermediates from the Julia–Kocienski reaction to change the reaction pathway from the traditional olefination to alkylation. Interesting halogen−π interactions between the halocarbon and aromatic donors were observed in the crystal structures of the products. The method could also be extended to the introduction of other fluorinated groups, such as −CFClBr, −CFClI, −CFBr₂, and −CFMeI, which opens up new avenues for the synthesis of a wide range of useful fluorinated products

Synthesis of Sulfoximines by Copper-Catalyzed Oxidative Coupling of Sulfinamides and Aryl Boronic Acids

A novel copper-catalyzed cross-coupling reaction of sulfinamides and aryl boronic acids is developed. The reaction is highly chemoselective and stereospecific, which allows mild synthesis of optically pure sulfoximines with broad scope and functional group tolerance. The utility of this method is demonstrated by the asymmetric synthesis of pharmaceutical intermediates

Copper-Mediated Fluoroalkylation of Aryl Iodides Enables Facile Access to Diverse Fluorinated Compounds: The Important Role of the (2-Pyridyl)sulfonyl Group

The (2-pyridyl)sulfonyl group was found to be a multifunctional group in the preparation of structurally diverse fluorinated products. It not only facilitates the copper-mediated (or catalyzed) cross-coupling reaction between α-fluoro sulfone 4a and aryl iodides, but also enables further transformations of the coupling products 2