Cyclic Allene Approach to the Manzamine Alkaloid Keramaphidin B.

We report an approach to the core of the manzamine alkaloid keramaphidin B that relies on the strain-promoted cycloaddition of an azacyclic allene with a pyrone trapping partner. The cycloaddition is tolerant of nitrile and primary amide functional groups and can be complemented with a subsequent retro-Diels-Alder step. These efforts demonstrate that strained cyclic allenes can be used to build significant structural complexity and should encourage further studies of these fleeting intermediates.

Arene C-H borylation strategy enabled by a non-classical boron cluster-based electrophile.

Introducing a tri-coordinate boron-based functional group (e.g., boronic ester) into an unactivated C-H bond in the absence of directing groups is an ongoing challenge in synthetic chemistry. Despite previous developments in transition metal-catalyzed and -free approaches, C-H borylation of sterically hindered arenes remains a largely unsolved problem to date. Here, we report a synthetic strategy of a two-step, precious metal-free electrophilic C-H borylation of sterically hindered alkyl- and haloarenes to generate aryl boronic esters. The first step relies on electrophilic aromatic substitution (EAS) induced by cage-opening of Cs2[closo-B10H10], forming a 6-Ar-nido-B10H13 product containing a B-C bond, followed by a cage deconstruction of arylated decaboranes promoted by diols. The combination of these two steps allows for the preparation of aryl boronic esters that are hardly accessible by current direct C-H borylation approaches. This reaction does not require any precious metals, highly-engineered ligands, pre-functionalized boron reagents, or inert conditions. In addition, the unique properties of a non-classical boron cluster electrophile intermediate, B10H13+, afford a regioselectivity with unique steric and electronic control without the undesirable side reactions.

Sulfide Oxidation by 2,6-Bis[hydroxyl(methyl)amino]-4-morpholino-1,3,5-triazinatodioxomolybdenum(VI): Mechanistic Implications with DFT Calculations for a New Class of Molybdenum(VI) Complex.

Sulfide oxidation is accomplished by a new class of dioxomolybdenum(VI) catalyst (1) that uses the tridentate 2,6-bis[hydroxyl(methyl)amino]-4-morpholino-1,3,5-triazine ligand to form a five-coordinate molybdenum(VI) center. Resonance Raman spectra show that the dioxo groups on the Mo(VI) oxygens readily exchange with water in an acetonitrile media that allows 18O labeling of catalyst 1. The model oxidation reaction was the conversion of thioanisole (2) to the corresponding sulfoxide with 4% of 1 using an equimolar amount of H2O2 in MeCN-d3. Oxygen-18 labeling experiments with either 18O-labeled 1 or 18O-labeled H2O2 are consistent with a sulfide oxygenation pathway that uses a η1-Mo(OOH) hydroxoperoxyl species (3). The hypothesized intermediate 3 is initially formed in a proton transfer reaction between 1 and H2O2. Oxidation is hypothesized via nucleophilic attack of the sulfide on 3 that is supported from a Hammett linear free-energy relationship for para-derivatives of 2. A Hammett reactivity constant (ρ) of -1.2 ± 0.2 was obtained, which is consistent with other ρ values found in prior sulfide oxidation reactions by group 6 complexes. An Eyring plot of the 2 oxidation by 1 gives an Ea of 63.0 ± 5.2 kJ/mol, which is slightly higher than that of a similar oxidation of 2 by the molybdenum(VI) complex, oxodiperoxo (pyridine-2-carboxylato)molybdate(VI) bis(pyridine-2-carboxylic acid) monohydrate (5). Computational modeling with density functional theory (DFT) of the complete reaction profile gave enthalpy and entropy of activations (64 kJ/mol and -120 J/mol·K, respectively) within 1 standard deviation of the experimental values, further supporting the hypothesized mechanism.