Conformational Preferences and Self-Template Macrocyclization of Squaramide-Based Foldable Modules

Abstract

Secondary squaramides have considerable potential as hydrogen bond donors and acceptors. In CHCl(3) both, anti- and syn-squaramide rotamers are observed by NMR. The energetic barrier for anti/syn mutual interconversion determined by complete band shape analysis is approximately 63 kJ mol(-1). As in proline derivatives, a low rotational barrier is crucial for the design of foldable modules. In this paper, folding based on the low rotational barrier of squaramides is driven by donor atoms (N or O) located in the gamma position of an alkyl chain of a secondary squaramide. We demonstrate that the resulting minimal module exists as a folded conformer through the formation of a nine-membered ring stabilized by intramolecular hydrogen bonding. Molecular mechanics calculations and NMR studies support the existence of these folded conformers. The intramolecularly hydrogen bonded conformers are clearly visible even in CHCl(3)-EtOH mixtures. Folding occurs even in pure ethanol. As an indirect test, we studied the effectiveness of macrocyclization reactions in pure ethanol that require an effective templating effect to take place. The high yields obtained support the dominant role of a folded conformer even in this solvent.

A New Macrocyclic Cryptand with Squaramide Moieties: An Overstructured CuII Complex That Selectively Binds Halides: Synthesis, Acid/Base‐ and Ligational Behavior, and Crystal Structures

“…[26] Under these conditions, cyclization and polymerization were avoided, obtaining 6 in high yield. Both compounds 4 and 6 can be used as building blocks for new molecular ligands of various topologies.…”

“…1,7-Dimethyl-1,4,7,10-tetra-azacyclododecane (1), [32] N-(p-toluenesulfonyl)aziridine (2), [36] and 3,4-diethoxy-3-cyclobutene-1,2-dione (5) [26] were prepared as described previously. All other chemicals were purchased at the highest quality commercially available.…”

Optimizing the Accuracy and Computational Cost in Theoretical Squaramide Catalysis: The Henry Reaction

“…In the KIE experiments, we observed inverse secondary KIE effects (Table 3), which is typical for reactions where the atom that performs the attack changes its hybridation from sp 2 to sp 3 (the C atom of MeNO2 in this reaction). [11] This suggests that the rate-limiting reaction step is the MeNO2 attack on the aldehyde (TS1).…”

Convergent Synthesis of Azabicycloalkenones using Squaric Acid as Platform

“…1:1 syn/anti-isomer mixtures at room temperature, due to the partial double bond character of the vinylogous amide C À N bonds. [10] With desired cyclobutenediones in hand, we explored the decarbonylative transformation of these substrates. Toward this aim, we decided to use rhodium complexes as catalyst precursors for following reasons: (1) rhodium complexes catalyze intramolecular PK reactions under a CO pressure of less than 1 atm, [11] (2) rhodium catalysts are able to utilize carbonyl compounds as CO sources, [3] and finally, (3) rhodium complexes have proved to be effective for the ring transformation of cyclobutanones via C À C bond cleavage.…”