Design and Synthesis of Bridging Chiral p–t‐Butylcalix[4]arene Tetrahydroisoquinolines and Their Application in Henry Reaction as Chiral Organocatalysts

A pair of bridging chiral p‐t‐butylcalix[4]arenes (2a and 2b) (were) synthesized from 1 through homologous anionic ortho‐Fries rearrangement, and optically resolved with (1S)‐(+)‐10‐camphorsulfonyl chloride as chiral auxiliary. Bridging chiral p‐t‐butylcalix[4]arene tetrahydroisoquinolines (9a and 9b) as chiral organocatalysts for Henry reaction were designed and synthesized through the structural modification of 2a and 2b, respectively. Compared to the catalytic enantioselectivity of the unmodified tertiary amine (4b: ∼0% ee and 63% yield), those of the tetrahydroisoquinoline derivatives (9b: up to 13.4% ee and 96% yield) were distinctly enhanced. Although the increase magnitude of the catalytic ee is not remarkable, these catalytic results prove that the conformation inversion of calix[4]arene skeleton and the rotational freedom reduction of catalytic amine group indeed bring beneficial effects on the catalytic stereoselectivity. Bridging chiral calix[4]arene 2b was successfully prepared from 1, and structurally modified into tetrahydroisoquinoline derivative 9 b. The catalytic result of 9b in Henry reaction (up to 13.4% ee and 96% yield) prove that the conformation inversion of calix[4]arene skeleton and the rotational freedom reduction of catalytic amine group indeed bring beneficial effects on the catalytic stereoselectivity.