Enantioselective Catalysis Coupled with Stereodivergent Cyclization Strategies Enables Rapid Syntheses of (+)‐Limaspermidine and (+)‐Kopsihainanine A

Enantioselective Pd‐catalyzed allylic alkylations of dihydropyrido[1,2‐a ]indolone (DHPI) substrates were used to construct the C20‐quaternary stereocenters of multiple monoterpene indole alkaloids. Stereodivergent Pictet–Spengler and Bischler–Napieralski cyclization/reduction cascades furnish the cis‐ and trans ‐fused azadecalin subunits present in Aspidosperma and Kopsia alkaloids, respectively, en route to highly efficient syntheses of (+)‐limaspermidine and (+)‐kopsihainanine A.     

Control of Vicinal Stereocenters through Nickel-Catalyzed Alkyl–Alkyl Cross-Coupling

Vicinal stereocenters are found in many natural and unnatural compounds. Although metal-catalyzed cross-coupling reactions of unactivated alkyl electrophiles are emerging as a powerful tool in organic synthesis, there have been virtually no reports of processes that generate, much less control, vicinal stereocenters. In this investigation, we establish that a chiral nickel catalyst can mediate doubly stereoconvergent alkyl–alkyl cross-coupling, specifically, reactions of a racemic pyrrolidine-derived nucleophile with cyclic alkyl halides (as mixtures of stereoisomers) to produce vicinal stereocenters with very good stereoselectivity.     

Reductive Decarboxylative Alkynylation of N‐Hydroxyphthalimide Esters with Bromoalkynes

A new method for the synthesis of terminal and internal alkynes from the nickel‐catalyzed decarboxylative coupling of N‐hydroxyphthalimide esters and bromoalkynes is presented. This reductive cross‐electrophile coupling is the first to use a C(sp)−X electrophile, and appears to proceed via an alkynylnickel intermediate. The internal alkyne products are obtained in yields of 41–95 % without the need for a photocatalyst, light, or a strong oxidant. The reaction displays a broad scope of carboxylic acid and alkyne coupling partners, and can tolerate an array of functional groups, including carbamate NH, halogen, nitrile, olefin, ketone, and ester moieties. Mechanistic studies suggest that this process does not involve an alkynylmanganese reagent and instead proceeds through nickel‐mediated bond formation.