An asymmetric aza-Diels-Alder and O-Michael addition sequence has been developed to construct chiral hydropyrano[2,3-b]pyridine derivatives with good yields and excellent stereoselectivity, by starting with N-Ts-1-aza-1,3-butadienes and aliphatic aldehydes tethered to an α,β-unsaturated ketone motif. A tandem O-Michael addition reaction was completed via acid catalysis.

An asymmetric aza-Diels–Alder and cation–olefin cyclization sequence has been developed to construct cyclopenta[b]piperidine skeletons with moderate yields and excellent stereoselectivities, by employing 5-enals and N-Ts-1-aza-1,3-butadienes as the starting materials. A designed domino cation–olefin/Friedel–Crafts reaction verified that the cyclization of N-Ts iminium ion underwent a stepwise cationic process.

The synthetically useful functionalized 2-substituted piperidines containing a lateral ketone group have been strategically accessed via an organocatalytic enantioselective intramolecular aza-Michael addition of enone carbamates, in which a novel internal substrate combination of the enone moiety as Michael acceptor and the carbamate moiety as Michael donor was revealed in asymmetric bifunctional organocatalysis. This heteroatom conjugate addition, which was realized by using a catalytic chiral Cinchona-based primary-tertiary diamine and an achiral Brønsted acid, mostly proceeded in high yield and good to excellent stereocontrol (up to 99% ee). This reaction provides an alternative catalytic asymmetric method for installing the stereogenic nitrogen-containing carbon center in functionalized 2-substituted piperidines, leading to the development of a straightforward and expeditious synthesis of some naturally occurring bioactive 2-substituted piperidine alkaloids.

A direct, asymmetric allylic alkylation of indenes withMorita–Baylis–Hillman (MBH) carbonates has been developed based on a Lewis base assisted Brønsted base catalysis strategy. This process is promoted by a modified cinchona alkaloid hydroquinidine (anthraquinone-1,4-diyl) diether [(DHQD)₂AQN] and gives rise to multifunctional chiral indene derivatives with moderate to excellent enantioselectivities (53–95 % ee), albeit in low to modest yields (27–71 %).

A Lewis base assisted Brønsted base catalysis (LBABB) strategy is applied for direct asymmetric vinylogous alkylation of allylic sulfones with Morita–Baylis–Hillman (MBH) carbonates, in which a strong Brønsted base, tert-butoxy anion, generated in situ from a tertiary amine catalyst and MBH carbonate, is crucial in activating unstabilized nucleophiles. The γ-regioselective alkylation products were obtained with good to excellent enantiomeric excess values when catalyzed by a modified cinchona alkaloid.

A facile method for the asymmetric synthesis of pyrimidinone derivatives was developed via an organocatalytic tandem aza-Michael addition–hemiaminal formation–dehydroxylation reaction, using N,N′-dialkyloxyurea as dinitrogen source (up to 97% ee). The transformations of hemiaminal intermediates to pyrimidinones with more complex structures have been also investigated.

An efficient tandem reaction for the asymmetric synthesis of six-membered spirocyclic oxindoles has been successfully developed through a formal [2+2+2] annulation strategy. The amine-catalysed stereoselective Michael addition of aliphatic aldehydes to electron-deficient olefinic oxindole motifs gave chiral C3 components, which were further combined with diverse electrophiles (activated olefins or imines) to afford spirocyclic oxindoles with versatile molecular complexity (up to six contiguous stereogenic centres, high diastereo- and enantioselectivities).

An efficient procedure for the asymmetric allylic amination of Morita–Baylis–Hillman carbonates with cyclic imides catalysed by commercially available cinchona alkaloids is reported. It proves to be a facile protocol that affords α-methylene β-amino esters with good-to-excellent enantioselectivities (up to 94 % ee) and in high yields (up to 97 %). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)