Reversible Twisting of Primary Amides via Ground State N–C(O) Destabilization: Highly Twisted Rotationally Inverted Acyclic Amides

Since the seminal
studies by Pauling in 1930s, planarity has become
the defining characteristic of the amide bond. Planarity of amides
has central implications for the reactivity and chemical properties
of amides of relevance to a range of chemical disciplines. While the
vast majority of amides are planar, nonplanarity has a profound effect
on the properties of the amide bond, with the most common method to
restrict the amide bond relying on the incorporation of the amide
function into a rigid cyclic ring system. In a major departure from
this concept, here, we report the first class of acyclic twisted amides
that can be prepared, reversibly, from common primary amides in a
single, operationally trivial step. Di-tert-butoxycarbonylation
of the amide nitrogen atom yields twisted amides in which the amide
bond exhibits nearly perpendicular twist. Full structural characterization
of a range of electronically diverse compounds from this new class
of twisted amides is reported. Through reactivity studies we demonstrate
unusual properties of the amide bond, wherein selective cleavage of
the amide bond can be achieved by a judicious choice of the reaction
conditions. Through computational studies we evaluate structural and
energetic details pertaining to the amide bond deformation. The ability
to selectively twist common primary amides, in a reversible manner,
has important implications for the design and application of the amide
bond nonplanarity in structural chemistry, biochemistry and organic
synthesis.