Planar Chiral PHANOLs as Double Hydrogen Bonding Donor Organocatalysts: Synthesis and Catalysis

Abstract

Abstract:4,12-Dihydroxy[2.2]paracyclophanediol (PHANOL; 1), and its para-substituted derivatives 2, 5 and 7, were found to catalyse Diels-Alder cycloadditions of a,b-unsaturated aldehydes or ketones with dienes and/or epoxide ring opening reactions with amines. The mode of catalysis by the PHANOLs is via double hydrogen bonding to the two sp 2 lone pairs of a carbonyl group or the two lone pairs of the epoxide. The order of activity of the PHANOLs for catalysis of the Diels-Alder reaction essentially correlates with the expected hydrogen-bond donor strength based on the degree of electron-withdrawing capability of the group(s) in the para position. In contrast, ortho-substituted PHANOLs 10, 11 and 14 were not active as catalysts due to steric interference with the double hydrogen bonding mode. 1 H NMR and IR spectral data for the various PHANOLs are discussed in support of the proposed double hydrogen bond mode.

Planar‐Chiral Thioureas as Hydrogen‐Bond Catalysts

“…[7] The activation of substrates by small organic molecules through covalent-or Brønsted acid interactions has been proved as a complementary approach to transition-metal catalysis. [8] Hydrogen-bond catalysis [9] has attracted considerable attention.…”

Beyond Simple Substitution Patterns – Symmetrically Tetrasubstituted [2.2]Paracyclophanes as 3D Functional Materials

“…The reactions to form 2 and 3 were elucidated by Cram and Reich . Compounds 70 , 74 , and 76 were elucidated by Braddock and co‐workers . Compound 72 was prepared by Gray and Boekelheide …”

“…In their synthesis of a hydrogen‐bonding chiral organocatalyst, Braddock and co‐workers found that the dinitration of 68 proceeds para selectively, as did the chorosulfination of diacetate 75 . The diacylation of diol 73 proceeded in the ortho position regioselectively . Gray and Boekelheide found the chloromethylation of diester 71 to proceed pseudo‐ gem regioselectively, when they elaborated on the synthesis of [2.2.2.2](1,2,4,5)cyclophane …”

Exploring the Potential of Diarylacetylenediols as Hydrogen Bonding Catalysts

“…12 A search for additional structural support for the interaction between phenolic diols and carbonyl groups uncovered an X-ray crystal structure reported by Saied, Simard, and Wuest of a diarylacetylenediol bound to a cyclohexanone by dual hydrogen bonds (Figure 1). 13 We recapitulated the essential features of this complex in silico using DFT calculations within Spartan'08 molecular modeling program.…”