Divergent Stereoselectivity in Phosphothreonine (pThr)-Catalyzed Reductive Aminations of 3‑Amidocyclohexanones

Phosphothreonine (pThr)-embedded
peptide catalysts are found to
mediate the reductive amination of 3-amidocyclohexanones with divergent
selectivity. The choice of peptide sequence can be used to alter the
diastereoselectivity to favor either the cis-product
or trans-product, which are obtained in up to 93:7
er. NMR studies and DFT calculations are reported and indicate that
both pathways rely on secondary interactions between substrate and
catalyst to achieve selectivity. Furthermore, catalysts appear to
accomplish a parallel kinetic resolution of the substrates. The facility
for phosphopeptides to tune reactivity and access multiple products
in reductive aminations may translate to the diversification of complex
substrates, such as natural products, at numerous reactive sites.