Asymmetric Organocatalytic Formal [2 + 2]-Cycloadditions via Bifunctional H-Bond Directing Dienamine Catalysis

A new concept in organocatalysis allowing for the construction
of cyclobutanes with four contiguous stereocenters with complete diastereo-
and enantiomeric control by a formal [2 + 2]-cycloaddition is presented.
The concept is based on simultaneous dual activation of α,β-unsaturated
aldehydes and nitroolefins by amino- and hydrogen-bonding catalysis,
respectively. A new bifunctional squaramide-based aminocatalyst has
been designed and synthesized in order to enable such an activation
strategy. The potential and scope of the reaction are demonstrated,
and computational studies which account for the stereochemical outcome
are presented.