The direct β-activation of saturated aldehydes and ketones has long been an elusive transformation. We found that photoredox catalysis in combination with organocatalysis can lead to the transient generation of 5π-electron β-enaminyl radicals from ketones and aldehydes that rapidly couple with cyano-substituted aryl rings at the carbonyl β-position. This mode of activation is suitable for a broad range of carbonyl β-functionalization reactions and is amenable to enantioselective catalysis.

A new method for the direct functionalization of diamondoids has been developed using photoredox and H-atom transfer catalysis. This C-H alkylation reaction has excellent chemoselectivity for the strong 3º C-H bonds of adamantanes in polyfunctional molecules. In substrate competition reactions, a reversal in selectivity is observed for the new H-atom transfer catalyst reported here when compared to six known photochemical systems. Derivatization of a broad scope of diamondoids and adamantane-containing drugs highlights the versatility and functional group tolerance of this C-H functionalization strategy.

An efficient anionic bicyclization of tryptamine-derived Zincke aldehydes forms the basis for a three-step route to the tetracyclic ABCE core of many Strychnos, Aspidosperma, and Iboga alkaloids. This powerful reaction is showcased in a five-step synthesis of the Strychnos alkaloid norfluorocurarine from tryptamine and pyridine.

Strychnine is synthesized via a longest linear sequence of six steps from commercially available starting materials. Key steps include a base-mediated intramolecular Diels-Alder reaction of a tryptaminederived Zincke aldehyde, a Ru-catalyzed trans-hydrosilylation of 1,4-butynediol, and a tandem Brook rearrangement/intramolecular conjugate addition reaction that affords the Wieland-Gumlich aldehyde.Scheme 1 Retrosynthetic analysis of strychnine demonstrates the powerfully simplifying Zincke aldehyde cycloaddition disconnection (M ¼ metal or suitable metal precursor).

A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.