Abstract
The discovery that a C2-symmetric bis(AMidine) [BAM] catalyst promotes an anti-selective addition of α-substituted α-nitro esters to imines is described, providing α-substituted α,β-diamino ester products with high diastereo- and enantioselectivity. When compared to the function of a BAM catalyst reported previously, the pair offer a rare example of diastereodivergence using a bifunctional Brønsted acid-base organocatalyst.
Highlights
The discovery that a C2-symmetric bis(AMidine) [BAM] catalyst promotes an anti-selective addition of asubstituted a-nitro esters to imines is described, providing a-substituted a,b-diamino ester products with high diastereo- and enantioselectivity
The enantioselective aza-Henry reaction[6] serves as a convergent approach to a,b-diamino acid derivatives, but its adaptation to a-alkyl-a-nitroester substrates (Scheme 1) is more rare, owing to the congestion provided by the additional substituent
We report the nding that a C2-symmetric ligand design, in combination with sterically hindered esters of a-nitro acids, can lead to highly anti-diastereoselective and enantioselective additions to N-Boc imine electrophiles
Summary
Methods to prepare enantioenriched a-amino acids are in demand, and there are few direct solutions to those bearing aalkyl substituents.[1] Fewer still are methods that deliver a,bdiamino acids bearing a-alkyl substituents.[2] These unnatural amino acids are desirable precursors to peptide sequences due to their effect on the conformation and activity of the peptide sequences into which they are incorporated.[3,4,5] The enantioselective aza-Henry (nitro-Mannich) reaction[6] serves as a convergent approach to a,b-diamino acid derivatives, but its adaptation to a-alkyl-a-nitroester substrates (Scheme 1) is more rare, owing to the congestion provided by the additional substituent Within this realm are the highly diastereoselective examples of the anti-selective reaction by Jorgensen,[7] Shibasaki,[8] Wu, and Huang-Dong.[10] In contrast, syn-selective reactions are the exception,[11] with reports by us[12] and Ooi.[13]. Scheme 1 Development of a diastereodivergent aza-Henry reaction of a-alkyl a,b-nitroesters: syn-selective (prior work) and anti-selective (this work) catalysts using a common bifunctional design
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