Enantioselective Synthesis of Inherently Chiral Calix[4]arenes via Palladium-Catalyzed Asymmetric Intramolecular C–H Arylations

Abstract

We report herein an efficient approach for the enantioselective synthesis of inherently chiral calix[4]arenes via palladium-catalyzed asymmetric intramolecular C−H arylations. Using a chiral bifunctional phosphine-carboxylate ligand, the inherent chirality on macrocyclic scaffolds was induced successfully, from which a wide range of calix [4]arenes with fluorenone motifs were obtained with good yields and excellent enantioselectivities (up to >99% ee). The synthetic utility of this method was demonstrated by diverse transformations of the products, thus substantially expanding the chemical space of chiral calix[4]arenes. Further investigations of photophysical and chiroptical properties revealed that calix[4]arenes bearing two fluorenone moieties displayed remarkable g lum values (up to 0.019), highlighting the great potential of inherent chirality in the development of organic optoelectronic materials.

Chiral Calix[3]pyrrole Derivatives: Synthesis, Racemization Kinetics, and Ring Expansion to Calix[9]‐ and Calix[12]pyrrole Analogues

“…As observed for calix [1]furan [2]pyrrole, [14] the ring expansion reaction of 1 proceeded in a regioselective fashion, with no evidence of other positional isomers being seen by NMR spectroscopy. However, in contrast to calix [3]pyrrole and calix [1]furan [2]pyrrole, which in our hands give calix [6]pyrrole-type macrocycles exclusively upon ring expansion, calix [1]furan [1]pyrrole [1]thiophene (1) was found to support formation of the calix [9]-and calix [12]pyrrole analogues 6 and 7. It thus appears to act as a useful synthetic precursor that allows access to large calix[n]pyrrole-type macrocycles that have…”

“…In pioneering work, Wang and Tong synthesized chiral heteracalix[4]aromatics from achiral chains composed of four different aromatic rings with excellent enantioselectivity [8] . Very recently, Cai and co‐workers employed asymmetric functionalization to generate inherently chiral analogues of calix[4]arenes [9] . However, the design parameters [10] leading to inherently chiral macrocycles are not yet well‐established, in part because the energy barrier for ring inversion varies widely and in ways that are not always apparent.…”

“…[8] Very recently, Cai and coworkers employed asymmetric functionalization to generate inherently chiral analogues of calix [4]arenes. [9] However, the design parameters [10] leading to inherently chiral macrocycles are not yet well-established, in part because the energy barrier for ring inversion varies widely and in ways that are not always apparent. New, inherently chiral motifs could help narrow this knowledge gap.…”

“…Compound 1 also acts as a useful synthetic precursor. Specifically, it undergoes acidcatalyzed ring cleavage and expansion to furnish calix [6]-, calix [9]-and calix [12]pyrrole-type macrocycles. The largest of these species was characterized by single crystal X-ray diffraction analysis and seen to adopt an achiral windmilllike conformation in the solid state.…”

Dynamic and Persistent Cyclochirality in Hydrogen-Bonded Derivatives of Medium-Ring Triamines

“…Furthermore, a sharp downfield (δ Η = 8.45 ppm for 1d) singlet was observed for the three N− H protons, consistent with a hydrogen-bonded environment. Taken together, these initial observations suggested that 1 and 2 possess a cyclic hydrogen-bonding network that enforces folding into a chiral, C 3 -symmetrical, bowl-shaped conformation (Figure 2c), 28,29 which must enantiomerize only slowly on the NMR timescale to preserve the four nonequivalent TACN proton environments.…”