Highly Enantioselective Catalytic Addition of Grignard Reagents to N‐Heterocyclic Acceptors

General methods to prepare chiral N‐heterocyclic molecular scaffolds are greatly sought after because of their significance in medicinal chemistry. Described here is the first general catalytic methodology to access a wide variety of chiral 2‐ and 4‐substituted tetrahydro‐quinolones, dihydro‐4‐pyridones, and piperidones with excellent yields and enantioselectivities, utilizing a single catalyst system.     

A Local‐Desymmetrization‐Based Divergent Synthesis of Quinine and Quinidine

Herein we report a novel synthetic entry to the legendary quinuclidine natural products quinine and quinidine. The developed strategy is based on the use of a symmetrical and nonstereogenic precursor to access quinine and quinidine through a “local‐desymmetrization” approach, in stark contrast conceptually to the preparation of stereodefined disubstituted piperidines (or their acyclic precursors) as featured in all past syntheses. The developed strategy also provided quinine and quinidine derivatives that could not be readily obtained through previous total syntheses or by modification of the naturally occurring substances.     

Total Synthesis of (−)‐Cephalotaxine and (−)‐Homoharringtonine via Furan Oxidation–Transannular Mannich Cyclization

Homoharringtonine and its congener cephalotaxine were synthesized. Oxidative ring‐opening of a furan unveils an amine‐tethered dicarbonyl, which undergoes spontaneous transannular Mannich cyclization. The cascade builds the full cephalotaxine substructure in a single operation in 60 % yield. A Noyori reduction enabled synthesis of the title compounds with excellent enantioselectivity (k_rel=278).     

Total Synthesis of Lycoricidine and Narciclasine by Chemical Dearomatization of Bromobenzene

The total synthesis of lycoricidine and narciclasine is enabled by an arenophile‐mediated dearomative dihydroxylation of bromobenzene. Subsequent transpositive Suzuki coupling and cycloreversion deliver a key biaryl dihydrodiol intermediate, which is rapidly converted into lycoricidine through site‐selective syn ‐1,4‐hydroxyamination and deprotection. The total synthesis of narciclasine is accomplished by the late‐stage, amide‐directed C−H hydroxylation of a lycoricidine intermediate. Moreover, the general applicability of this strategy to access dihydroxylated biphenyls is demonstrated with several examples.     

Synthesis of Atisine,Ajaconine, Denudatine,and Hetidine Diterpenoid Alkaloids by a Bioinspired Approach

A unified approach to four different (atisine, ajaconine, denudatine, and hetidine) diterpenoid alkaloid skeletons was developed and applied to the total synthesis of the natural products dihydroajaconine ( 2 , atisine type) and gymnandine ( 4 , denudatine type). The synthesis features a biogenetically inspired strategy that relies on C−H oxidation, aza‐pinacol coupling, and aza‐Prins cyclization as key steps.