Functionalized and Degradable Polyphthalaldehyde Derivatives.

Polymers that depolymerize back to monomers can be repeatedly chemically recycled, thereby reducing their environmental impact. Polyphthalaldehyde is a metastable polymer that can rapidly and quantitatively depolymerize due to its low ceiling temperature. However, the effect of substitution on the physical and chemical properties of polyphthalaldehyde derivatives has not been systematically studied. Herein, we investigate the cationic polymerization of seven o-phthalaldehyde derivatives and demonstrate that judicious choice of substituent results in materials with a wide range of ceiling temperatures (<-60 to 106 °C) and decomposition temperatures (109-196 °C). We anticipate that these new polymers and their derivatives will enable researchers to access degradable materials with tunable thermal, physical, and chemical properties.

Ni-Catalyzed Carbon-Carbon Bond-Forming Reductive Amination.

This report describes a three-component, Ni-catalyzed reductive coupling that enables the convergent synthesis of tertiary benzhydryl amines, which are challenging to access by traditional reductive amination methodologies. The reaction makes use of iminium ions generated in situ from the condensation of secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo reaction with several distinct classes of organic electrophiles. The synthetic value of this process is demonstrated by a single-step synthesis of antimigraine drug flunarizine (Sibelium) and high yielding derivatization of paroxetine (Paxil) and metoprolol (Lopressor). Mechanistic investigations support a sequential oxidative addition mechanism rather than a pathway proceeding via α-amino radical formation. Accordingly, application of catalytic conditions to an intramolecular reductive coupling is demonstrated for the synthesis of endo- and exocyclic benzhydryl amines.

Rate-limiting step of the Rh-catalyzed carboacylation of alkenes: C-C bond activation or migratory insertion?

Rhodium-catalyzed intramolecular carboacylation of alkenes, achieved using quinolinyl ketones containing tethered alkenes, proceeds via the activation and functionalization of a carbon-carbon single bond. This transformation has been demonstrated using RhCl(PPh(3))(3) and [Rh(C(2)H(4))(2)Cl](2) catalysts. Mechanistic investigations of these systems, including determination of the rate law and kinetic isotope effects, were utilized to identify a change in mechanism with substrate. With each catalyst, the transformation occurs via rate-limiting carbon-carbon bond activation for species with minimal alkene substitution, but alkene insertion becomes rate-limiting for more sterically encumbered substrates. Hammett studies and analysis of a series of substituted analogues provide additional insight into the nature of these turnover-limiting elementary steps of catalysis and the relative energies of the carbon-carbon bond activation and alkene insertion steps.

Nickel-catalyzed enantioselective arylation of pyridine.

We report an enantioselective Ni-catalyzed cross coupling of arylzinc reagents with pyridiniumions formed in situ from pyridine and a chloroformate. This reaction provides enantioenriched 2-aryl-1,2-dihydropyridine products that can be elaborated to numerous piperidine derivatives with little or no loss in ee. This method is notable for its use of pyridine, a feedstock chemical, to build a versatile, chiral heterocycle in a single synthetic step.