A highly enantio- and diastereoselective synthesis of indolo- and benzoquinolizidine compounds has been developed through the formal aza-Diels–Alder reaction of enones with cyclic imines. This transformation is catalyzed by a new bifunctional primary aminothiourea that achieves simultaneous activation of both the enone and imine reaction components.

We describe the rational design of a linked, bis-thiourea catalyst with enhanced activity relative to monomeric analogs in a representative enantioselective anion-abstraction reaction. Mechanistic insights guide development of this linking strategy to favor substrate activation though the intramolecular cooperation of two thiourea subunits while avoiding nonproductive aggregation. The resulting catalyst platform overcomes many of the practical limitations that have plagued hydrogen-bond donor catalysis and enables use of catalyst loadings as low as 0.05 mol %. Computational analyses of possible anion-binding modes provide detailed insight into the precise mechanism of anion-abstraction catalysis with this pseudo-dimeric thiourea.

A catalytic, enantioselective synthesis of (+)-reserpine is reported. The route features a highly diastereoselective, chiral catalyst-controlled formal aza-Diels–Alder reaction between a 6-methoxytryptamine-derived dihydro-β-carboline and an enantioenriched α-substituted enone to form a key tetracyclic intermediate. This approach addresses the challenge of setting the C3 stereogenic center by using catalyst control. Elaboration of the tetracycle to (+)-reserpine includes an intramolecular aldol cyclization and a highly diastereoselective hydrogenation of a sterically hindered enoate.

The asymmetric acylation of meso 2-substituted-1,3-propanediols using an amphoteric chiral dinuclear zinc catalyst is described. It is has been demonstrated that both 2-alkyl-and 2-aryl-1,3-propanediols can be desymmetrized in high yields and enantioselectivities using the same family of ligands. Given that both antipodes of the chiral catalyst are available, both enantiomers of the desymmetrized product can be obtained from the same starting material.The synthetic utility of the desymmetrized products has been demonstrated by the synthesis of several chiral building blocks with high enantiomeric purities.

Highly enantio- and diastereoselective transannular ketone-ene reactions are catalyzed by a new chromium(III) triflate tridentate Schiff-base complex. Electronically unactivated keto-olefins undergo hetero-ene reactions at ambient temperature to afford enantioenriched bicyclic alcohols, common structural motifs in natural products. The kinetic resolution of a configurationally stable planar-chiral cyclodecenone is also described.