ChusSpringsteen

A carbenoid species consists of a tetrasubstituted carbon atom bearing a leaving group X and a metal–carbon bond, from which extrusion of X triggers the elimination/transfer of the CR¹R² unit. This is the case of the largely known Simmons–Smith reaction (based on Zn) or the more recent gold-based carbenoid LAuCH₂Cl described by Echavarren and co-workers. In the context of metal-induced carbene transfer from a diazo compound, a clear distinction must be made between the transient carbenoid and metal–carbene intermediates. For more information see the Concept article by A. Caballero and P. J. Pérez on page 14389 ff.

Hydrocarbons are still the most important precursors of functionalized organic molecules, which has stirred interest in the discovery of new C−H bond functionalization methods. We describe herein a new step-economical approach that enables C−C bonds to be constructed at the terminal position of linear alkanes. First, we show that secondary alkyl bromides can undergo in situ conversion into alkyl zinc bromides and regioconvergent Negishi coupling with aryl or alkenyl triflates. The use of a suitable phosphine ligand favoring Pd migration enabled the selective formation of the linear cross-coupling product. Subsequently, mixtures of secondary alkyl bromides were prepared from linear alkanes by standard bromination, and regioconvergent cross-coupling then provided access to the corresponding linear arylation product in only two steps.

Remote control: Secondary alkyl bromides underwent regioconvergent Barbier–Negishi coupling with aryl triflates in the presence of a phosphine ligand favoring Pd migration to give linear products with good to high linear/branched selectivity (see scheme). This procedure was also applied to mixtures of secondary alkyl bromides, prepared from linear alkanes by standard bromination.

The successful application of dihydropyrido[1,2-a]indolone (DHPI) substrates in Pd-catalyzed asymmetric allylic alkylation chemistry facilitates rapid access to multiple alkaloid frameworks in an enantioselective fashion. Strategic bromination at the indole C3 position greatly improved the allylic alkylation chemistry and enabled a highly efficient Negishi cross-coupling downstream. The first catalytic enantioselective total synthesis of (−)-goniomitine, along with divergent formal syntheses of (+)-aspidospermidine and (−)-quebrachamine, are reported herein.

Magnum (DH)PI: Application of dihydropyrido[1,2-a]indolone (DHPI) substrates in Pd-catalyzed asymmetric allylic alkylation chemistry enables rapid access to multiple alkaloid frameworks in an enantioselective fashion. The first catalytic enantioselective total synthesis of (−)-goniomitine, along with divergent formal syntheses of (+)-aspidospermidine and (−)-quebrachamine are reported.