Regioselectivity Change in the Organocatalytic Enantioselective (3+2) Cycloaddition with Nitrones through Cooperative Hydrogen-Bonding Catalysis/Iminium Activation.

The reaction of nitrones with enals through iminium activation can be modulated by using cooperative hydrogen-bonding catalysis to induce the participation of a nitrone ylide (C-N-C) instead of the classical C-N-O dipole. As a consequence, N-hydroxypyrrolidines are obtained, rather than the expected isoxazolidines. The reaction proceeds smoothly and high enantioselectivities are observed in all cases. By using the appropriate substrate, polysubstituted pyrrolidines incorporating quaternary stereocenters can be efficiently prepared.

Azomethine Ylides from Nitrones: Using Catalytic nBuLi for the Totally Stereoselective Synthesis of trans-2-Alkyl-3-oxazolines.

The cycloaddition of azomethine ylide N-oxides (nitrone ylides) with aldehydes provides 3-oxazolines in a completely stereoselective manner in the presence of a catalytic amount of n-butyllithium. The process involves an initial nucleophilic attack on the aldehyde, followed by intramolecular oxygen addition to the nitrone moiety and lithium-assisted elimination of water, regenerating the catalytic species. Various Li-based catalytic systems are possible and the in situ generated water is required for continuing the catalytic cycle. The best results are observed with 20 mol % of n-butyllithium, whereas the use of stoichiometric amounts inhibit the rate of catalysis. Experimental, spectroscopic, and computational mechanistic studies have provided evidence of lithium-ion catalysis and rationalized several competing catalytic pathways.