Highly Enantioselective Desymmetrization of Centrosymmetric pseudo - para -Diformyl[2.2]paracyclophane via Asymmetric Transfer Hydrogenation

Marie-Leonie Delcourt (1) , Simon Felder (1) , Erica Benedetti (1) , Laurent Micouin (1)

1 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques

Herein we describe the desymmetrization of a centrosymmetric pseudo-para-diformyl[2.2]paracyclophane based on Noyori asymmetric transfer hydrogenations (ATH). The reduction proceeds smoothly in the presence of commercially available ruthenium complexes to afford a monohydroxymethylated product in good yields and excellent enantioselectivities (up to 74% isolated yield and 99% ee). Our approach is operationally simple and can be run in gram-scale without any significant loss in the reaction efficiency. This desymmetrization strategy allows an easy access to an enantiopure compound bearing on each aromatic ring of the pCp core different reactive groups suitable for regioselective orthogonal postfunctionalization. T he compound [2.2]paracyclophane (pCp) and its derivatives constitute a well-known class of aromatic compounds characterized by an unusual three-dimensional framework and unique through-space interactions between their stacked aromatic subunits. 1 First discovered in the late 1940s, 2 these molecules find nowadays wide applications in material sciences for the development of through-space conjugated polymers 3 and optoelectronic devices. 4 Substituted paracyclophanes can show planar chirality due to their rigid structure which hinders the rotation of their two benzene rings. 5 This characteristic recently proved to be particularly useful for the application of pCps as chiral inductors in asymmetric catalysis and stereoselective synthesis. 1,6 Enantiopure paracyclophanes are also increasingly employed as building blocks for the development of circularly polarized light-emitting materials. 7 Over the years, optically active paracyclophanes have mostly been prepared by classical stoichiometric resolution methods and/or chromatographic separation on chiral stationary phases. 8 On the contrary, only few catalytic procedures for accessing enantioenriched pCps have been reported in the literature so far. 9 The development of new catalytic asymmetric processes allowing an efficient synthesis of planar-chiral paracyclophane derivatives is therefore highly desirable in order to expand the range of application of these molecules in different research areas. Recently, we were able to demonstrate that catalytic kinetic resolutions of racemic pCps could be employed to efficiently access valuable synthetic intermediates in their enantiopure form (Scheme 1a). 10 In order to overcome the limitation of 50% yield associated with the resolution strategy, 11 our efforts are currently directed toward the preparation of enantiopure pCp key intermediates through scalable desymmetrization reactions. The classical desymmetrization approaches involve asym-metric transformations capable of differentiating the enantio-topic functional groups of meso compounds with internal

Mots clés: [22]paracyclophanes; planar chirality; centrosymmetric compounds; desymmetrization; asymmetric transfer hydrogenation

Domaines: Chimie; Chimie organique; Catalyse

Marie-Leonie Delcourt, Simon Felder, Erica Benedetti, Laurent Micouin. Highly Enantioselective Desymmetrization of Centrosymmetric pseudo - para -Diformyl[2.2]paracyclophane via Asymmetric Transfer Hydrogenation. ACS Catalysis, 2018, 8 (7), pp.6612-6616. ⟨10.1021/acscatal.8b01872⟩. ⟨hal-02113395⟩