Generality-Driven Catalyst Development: A Universal Catalyst for Enantioselective Nitroalkene Reduction

Cracking
the selectivity–generality paradox is among the
most pressing challenges in asymmetric catalysis. This obstacle prevents
the immediate and successful translation of new methods to diverse
small molecules. This is particularly rate-limiting for therapeutic
development, where availability and structural diversity are often
critical components of successful campaigns. Here we describe the
union of generality-driven enantioselective catalysis and the preparation
of diverse peptidomimetics. A single new organocatalyst provides high
selectivity and substrate generality that is matched only by a combination
of metal and organocatalysts. Within organocatalysis, this discovery
breaks a 16-year monolithic paradigm, uncovering a powerful new scaffold
for enantioselective reduction with behavior that suggests the recognition
of a nitroethylene minimal catalaphile.