Synergistic Copper/Enamine Catalysis for the Regio-, Stereo-, and Enantioselective Intermolecular α-Addition of Aldehydes to Allenamides

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.1 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 N-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.

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Stereoselective organocatalytic oxidation of alcohols to enals: a homologation method to prepare polyenes

Chemical Communications ◽

10.1039/c5cc10093c ◽

2016 ◽

Vol 52 (17) ◽

pp. 3532-3535 ◽

Cited By ~ 10

Author(s):

Xiaobei Chen ◽

Yinan Zhang ◽

Huixin Wan ◽

Wei Wang ◽

Shilei Zhang

Keyword(s):

Oxidation Of Alcohols ◽

Enamine Catalysis ◽

Novel Method

A novel method for organocatalytic oxidation through oxidative enamine catalysis was developed with excellent compatibility for the direct syntheses of enals from simple saturated alcohols.

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