Anion‐π Catalysis: Focus on Nonadjacent Stereocenters

Abstract

In Memory of Gilbert StorkAnion-p interactions have been recently introduced to catalysis with the idea to stabilize anionic intermediates on p-acidic surfaces. Realized examples include enolate, enamine and iminium chemistry, domino processes and DielsAlder reactions. Moving on from the formation of contiguous stereogenic centers on p-acidic surfaces, herein we report the first asymmetric anion-p catalysis of cascade reactions that afford nonadjacent stereocenters. Conjugate addition-protonation of achiral disubstituted enolate donors to 2-chloroacrylonitrile generates 1,3-nonadjacent stereocenters with moderate enantioselectivity and diastereoselectivity. The explored catalysts operate with complementary naphthalenediimide and fullerene surfaces with highly positive quadrupole moments and high polarizability, respectively, and proximal amine bases. We find that anion-p catalysts can increase the diastereoselectivity of the reaction beyond the maximal 1:4.0 dr with conventional catalysts to maximal 5.3:1 dr on the large fullerene surfaces. The enantioselectivity of anion-p catalysts, best on the confined naphthalenediimide surfaces with strong quadrupole moment, exceed the performance of conventional catalysts except for comparable results with a new, most compact, surprisingly powerful bifunctional control catalyst. Simultaneously increased rates and stereoselectivities compared to control catalysts without p-acidic surface support that contributions of anion-p interactions to the catalytic cascade process are significant.

Mechanosensitive Oligodithienothiophenes: Transmembrane Anion Transport Along Chalcogen‐Bonding Cascades

“…The complementary π slides composed of three π ‐acidic naphthalenediimides caused the expected inversion from cation to anion selectivity ( Figure ,c ) . The promise of anion‐ π interactions in synthetic transport systems has since been validated in many variations, also with very small systems, and extended to catalysis …”

Synergistic Anion–(π)n–π Catalysis on π-Stacked Foldamers

“…Using electric fields, we have demonstrated the importance of polarizability in anion−π catalysis . In a complementary approach, large and highly polarizable fullerene surfaces supported by induced aromatic dipoles rather than inverted quadrupole moments have been found to provide access to anion−π interactions of highest functional relevance . Toward polarizing the π-acidic surfaces by charge delocalization over systems as large as possible, we here introduce synergistic anion–(π) n –π interactions in π-stacked foldamers.…”

Anion–π Catalysis Enabled by the Mechanical Bond**

“…A key limitation of the structures presented appears to be their basicity which, although enhanced by the mechanical bond, remains low enough that even in the case of relatively acidic substrate 7 , rotaxanes 4 a and 4 c are inactive in THF and reactions mediated by 4 b are slow at reduced temperatures in CDCl 3 . Indeed, attempts to apply these catalysts to other previously studied anion‐π catalysed reactions with less acidic substrates [9b, 11e, 32] revealed reaction rates that were impractically slow, requiring multiple weeks to observe even trace amounts of product (Supporting Information section S9). Future work will focus on overcoming this limitation by engineering more basic functional groups into the axle of suitable structures, as well as adding electron‐withdrawing groups to the NDI core to enhance π‐acidity, [8a] both while maintaining the π–π stacking interactions that deliver high polarizability and thus strong anion‐π interactions for catalysis.…”