Diastereodivergent synthesis of enantioenriched α,β-disubstituted-γ-butyrolactones via cooperative N-heterocyclic carbene/Ir catalysis

Transition-metal-catalyzed allylic substitution is one of the most powerful and frequently used methods in organic synthesis. In particular, palladium-catalyzed allylic functionalization has become a well-established strategy to construct carbon-carbon or carbon-heteroatom bonds, and its utility has been demonstrated in natural product synthesis, drug discovery and materials science. Several methods have been developed to generate -allylpalladium complexes through ionic mechanisms; however, these methods typically require either prefunctionalized starting materials or stoichiometric oxidants, which naturally limits their scope. Here we show a radical approach for the generation of -allylpalladium complexes by employing N-hydroxyphthalimide esters as bifunctional reagents in combination with 1,3-dienes. Using this strategy, we report the 1,4-aminoalkylation of dienes. The remarkable scope and functional group tolerance of this redox-neutral and mild protocol was demonstrated across > 60 examples. The utility of this strategy was further demonstrated in radical cascade reactions and in the late-stage modification of drugs and natural products.

Cyclization and annulation reactions initiated by ring-opening of small rings, especially cyclopropanes and cyclobutanes are now well-established in synthetic chemistry. Nevertheless, the potential of aminocyclopropanes and cyclobutanes, an important subclass for the synthesis of nitrogen-rich building blocks, has remained unexploited for a long time, despite important pioneering results. In the last decade, the situation has changed dramatically and new catalytic methods have emerged both for cyclization and annulation reactions. The purpose of this feature article is to present recent progress in this area, including our own work using donoracceptor substituted cyclopropanes and cyclobutanes.

A catalytic hydroamidation of alkynes with isocyanates using alkyl bromides as hydride sources has been developed. The method turns parasitic β-hydride elimination into a strategic advantage, rapidly affording acrylamides with excellent chemo- and regioselectivity.