<p></p><p>Chiral molecules with their defined 3-D structures are of
paramount importance for the study of chemical biology and drug discovery.
Having rich structural diversity and unique stereoisomerism, chiral molecules
offer a large chemical space that can be explored for the design of new
therapeutic agents.<sup>1</sup> In practice, chiral architectures are usually prepared from
organometallic and organocatalytic processes where a transition metal or an
organocatalyst is tailor-made for a desired reaction. As a result, developing a
method that enables rapid assembly of chiral complex molecules under a metal-
and organocatalyst-free condition represents a daunting challenge. Here we
developed a straightforward one-pot procedure to create a chiral 3-D structure
from 2-D structures and an amino acid without any chiral catalyst. The center
of this research is the design of a <a>special chiral
spiroimidazolidinone cyclohexadienone intermediate</a>, a merger of a chiral
reactive substrate with multiple nucleophillic/electrophillic sites and a
transient organocatalyst. <a>This unique substrate-catalyst
(“sub-catalyst”) dual role of the intermediate was displayed in its
aza-Michael/Michael cascade reaction with an </a>α,β-unsaturated aldehyde under an iminium/enamine catalysis.
<a>The enhanced co-ordinational proximity of the chiral
substrate and catalyst</a> in the transition state resulted in a substantial
steric discrimination and an excellent overall diastereoselectivity. Aza-tricylic molecules with six contiguous
stereocenters were assembled from <i>N</i>-alkylated aminophenols, α,β-unsaturated aldehydes and chiral α-amino acids under a hidden
“sub-catalysis” where the strategically produced “sub-catalyst” does not
present in initial components of the reaction. The success of this methodology
will pave the way for many efficient preparations of chiral complex molecules.</p><br><p></p>
One-pot three-component synthesis of quinoxaline and phenazine ring systems using Fischer carbene complexes
