Efficient and Scalable Kinetic Resolution of Racemic 4‐Formyl[2.2]paracyclophane via Asymmetric Transfer Hydrogenation

Herein we wish to report a new non‐enzymatic kinetic resolution of racemic 4‐formyl[2.2]paracyclophane based on Noyori asymmetric transfer hydrogenations (KR‐ATH). Our approach, which provides an efficient access to enantiopure (R_p)‐ and (S_p)‐4‐formyl[2.2]paracyclophane (>99% ee, 39% and 41% isolated yields, respectively), is operationally simple and can be run on the gram‐scale thus confirming the practical applicability of this method.

     

Efficient Modular Synthesis of Isomeric Mono‐ and Bispyridyl[2.2]paracyclophanes by Palladium‐Catalyzed Cross‐ Coupling Reactions

Pyridyl‐substituted [2.2]paracyclophanes build a multifunctional structural motif that is useful in material chemistry, catalysis and for luminescent structures. Nonetheless, there is still a lack of general methods for the synthesis of these structures tolerating easily accessible bromides as well as different isomeric pyridyl groups. Hence the coupling of functionalized [2.2]paracyclophanes with various substituted and functionalized pyridyl derivatives was achieved using Stille, Suzuki and Kumada coupling conditions. Hereby the Stille coupling of a [2.2]paracyclophane is presented as a versatile reaction for the formation of heteromeric [2.2]paracyclophane‐containing biaryl structures.

     

Development of Chiral Phosphoric Acids based on Ferrocene‐Bridged Paracyclophane Frameworks

This work deals with the development of a new family of planar chiral phosphoric acids based on a ferrocenophane/paracyclophane scaffold. The synthetic approach has been improved by taking advantage of a chiral phosphorylating agent to access enantiomerically enriched acids via diastereomers separation. These phosphoric acids have been used as catalysts for the enantioselective H‐transfer reduction of α‐substituted quinolines with Hantzsch esters. Optimization of both the catalyst and the Hantzsch reductant allowed ee values in the range 82–92% to be attained starting from α‐arylquinolines.

     

Second‐Generation N,O‐[2.2]Paracyclophane Ketimine Ligands for the Alkenylzinc Addition to Aliphatic and Aromatic Aldehydes: Scope and Limitations

Second generation N,O‐[2.2]paracyclophane ketimine ligands were investigated for their ability to catalyze the 1,2‐addition of alkenylzinc reagents to aliphatic and aromatic aldehydes with special focus on functionalized substrates. For aliphatic aldehydes, which have always been challenging in this field, remarkably high enantiomeric excesses could be determined (50–95 % ee). However, alkenylzinc reagents bearing heteroatoms proved to be demanding substrates for this system.     

High-Pressure Diels-Alder Reaction: Preparation of [2.2]Paracyclophane Derivatives

High-pressure Diels-Alder cycloaddition reactions of 5-ethenyl[2.2]indeno-paracyclophane (1) with 1,4-benzoquinone (2), N-phenylmaleimide (3), and 2-inden-1-one (4) have been studied. Attempts to convert the cycloadducts into the corresponding aromatic helicenophanes failed. All new compounds were characterized by extensive nuclear magnetic resonance (NMR) investigations.     

Palladium‐Catalyzed C?H Bond Acetoxylation: An Approach to ortho‐Substituted Hydroxy[2.2]paracyclophane Derivatives

The palladium‐catalyzed direct C H bond acetoxylation of [2.2]paracyclophanes has been investigated. Various mono‐ and disubstituted [2.2]paracyclophanes were subjected to typical Sanford acetoxylation conditions. Oxime ethers, an oxime acetate, a pyridine, and a pyrazole with [2.2]paracyclophane cores underwent direct ortho‐acetoxylation in good to excellent yields using 1–5 mol% of palladium(II) acetate in combination with iodobenzene diacetate as oxidant. The reactions could be performed on a multigram scale, and the ortho‐acetoxylated [2.2]paracyclophanes were suitable for further functionalizations affording a hydroxy[2.2]paracyclophane derivative and a planar chiral benzoxazole.     

The Synthesis of Pseudo‐Geminal,Pseudo‐Ortho and Ortho Hydroxy‐oxazolinyl[2.2]paracyclophanes for Use as Ligands in Asymmetric Catalysis

Synthetic routes to pseudo‐geminal, pseudo‐ortho and ortho hydroxy‐oxazolinyl[2.2]paracyclophanes (and the diastereoisomers of each) for use as N,O ligands in asymmetric catalysis have been devised. The substitution pattern was found to have a strong effect on the rate and enantioselectivity of the formed catalyst in the addition of diethylzinc to benzaldehyde.     

Second‐Generation Paracyclophane Imine Ligands for the Dialkylzinc Addition to Aldehydes. Optimization of the Branched Side Chain leads to Improvement for Aliphatic Aldehydes

Two novel diastereomeric [2.2]paracyclophane ketimine ligands (S_P,S)‐ 2 and (R_P,S)‐ 2 , which unite a planar chiral element and a central chiral element, were used towards the enantioselective diethylzinc addition onto aliphatic aldehydes. These improved second‐generation ligands, which are stable in air and water and are easy to obtain, showed significant improvements with respect to the ligands that were previously used.