Propargylamines are important intermediates for the synthesis of polyfunctional amino derivatives and natural products and biologically active compounds. The classic method of synthesizing chiral propargylamines involves the asymmetric alkynylation of imines. Here, we report a significant advance in the catalytic asymmetric Mannich-type synthesis of propargylamines through catalytic asymmetric addition of carbon nucleophiles to C-alkynyl imines, culminating in a highly syn-selective catalytic asymmetric Mannich reaction of C-alkynyl imines that provide syn-configured propargylamines with two adjacent stereogenic centres and a transition metal-free organocatalytic asymmetric approach to β-alkynyl-β-amino acids with high efficiency and practicality, via a chiral Brønsted base-catalysed asymmetric Mannich-type reaction of in situ generated challenging N-Boc C-alkynyl imines from previously unreported C-alkynyl N-Boc-N,O-acetals, with α-substituted β-keto esters and less-acidic malonate (thio)esters as nucleophiles, respectively. A catalytic activation strategy is also disclosed, which may have broad implications for use in catalysis and synthesis.

The catalytic enantioselective and divergent total syntheses of Aspidosperma alkaloids (+)-10-oxocylindrocarpidine 7, (+)-cylindrocarpidine 1, (-)-N-acetylcylindrocarpinol 6, and (+)-aspidospermine 8 have been accomplished in 11 steps from a common precursor (15) on the basis of a highly concise route. The route features three metal-catalyzed reactions, including the key Pd-catalyzed decarboxylative asymmetric allylation of carbazolones developed in our laboratory. Our syntheses, using a combination of C-H activation, enantioselective catalysis, and collective synthesis, represent the first total synthesis of 10-oxocylindrocarpidine and the first asymmetric total synthesis of cylindrocarpidine and N-acetylcylindrocarpinol.

A novel catalytic enantioselective synthesis of functionalized 1,3-enynes has been developed featuring the design and synthesis of conjugated nitro dienynes as a useful new class of Michael acceptors. Moreover, a simple, yet flexible catalytic cascade approach to functionalized enantioenriched acyclic α,β-enones and cyclic dienones has also been developed.

The first method for the asymmetric synthesis of C3-monosubstituted chiral carbazolones, structural motifs common in medicinal chemistry, has been achieved using Pd-catalyzed decarboxylative protonation of carbazolones. This methodology has been applied to the first catalytic enantioselective formal synthesis of (-)-aspidofractinine with step economy and simplicity.