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

Abstract

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. Keywords: alkenylzinc reagents; asymmetric catalysis; chiral allylic alcohols; N,O ligands; paracyclophanes Chiral allylic alcohols are important targets in organic synthesis, especially in natural product synthesis. As intermediates they can be used in further reactions such as allylic substitution, dihydroxylation, ene reaction, cyclopropanation, bromination, or epoxidation. However, the lack of a powerful ligand system impedes the use of the 1,2-addition of alkenylzinc reagents to aldehydes as a key step in natural product synthesis because highly functionalized substrates must be tolerated and high enantiomeric excesses must be achieved.[1] The rare examples in the literature show mostly the use of divinylzinc and substrateinduced diastereoselectivity. [2] In the case of substrate toleration, the catalyzed alkenylzinc addition could be an appropriate method because of the relatively low reactivity of zinc diorganyls towards aldehydes and ketones in comparison to other organometal compounds.[3] However, investigations in this field are few. In contrast, alkyl transfer to aromatic aldehydes is one of the most studied enantioselective catalytic reactions, yet there are only a few examples with high enantiomeric excesses for aliphatic aldehydes.[4] The alkenylzinc transfer is even less investigated; however, interest in this reaction has increased throughout the last years. [5][6][7][8][9][10][11][12] One method elaborated by Oppolzer and Radinov produces mixed alkyl-alkenylzinc species in situ using a transmetalation protocol involving hydroboration of alkynes.[2]paracyclophane-based ligands produce results ranging from good to excellent for this type of reaction, whereas the scope is limited to aromatic aldehydes and fully branched aliphatic aldehydes.[11] Wipf et al. also reported the preparation of alkenylzinc reagents via transmetalation but using zirconium as metal. [9] A comprehensive survey of [2.2]paracyclophanebased ligands can be found in recent reviews.[13] The use of planar-chiral and central-chiral ligands based on paracyclophane systems has emerged en masse since the disclosures by Belokon, Rozenberg et al., [14,15] the Berkessel group, [16] and most notably the Hopf group.[17] Within the last years, various new paracyclophane ligands have been used for asymmetric catalysis. [18][19][20] In particular, the asymmetric 1,2-addition reaction of organozinc compounds such as alkyl-, [21] alkenyl-, [11] and alkynylzinc [22] reagents with aldehydes or imines, [21] respectively, can be efficiently controlled by the use of...

Stereoselective Synthesis of (2Z,4E)-2,4-Pentadien-1-ols via Sequential 1,4-Elimination Reaction and [1,2]-Wittig Rearrangement Starting from (E)-4-Alkoxy-2-butenyl Benzoates

“…After insoluble substance was filtered off through a bed of Celite, the solvent was evaporated. The residue was passed through a short silica gel column (hexane/AcOEt = 2/1) to afford the almost pure ( E )-2-buten-1-ol 5a (2.53 g). This material was used for the conversion to the corresponding benzoate 1a without further purification.…”

Selective synthesis of the 2-hydroxyferrocene-aldimine enantiomers—extended planar chiral analogues of the “flat” salicylaldimine ligand family

“…16 Principally, this could be achieved by forming p-arene metal complexes of, for example, the system 1. 17 We here want to present and discuss an alternative approach, namely the development of viable syntheses to the corresponding 2-hydroxyferrocene aldimines and their anions (2 -), the "ferrocene-saliminato" ligands.…”

Chiral Cooperativity and Solvent-Induced Tautomerism Effects in Electronic Circular Dichroism Spectra of [2.2]Paracyclophane Ketimines

“…The diastereomers of compound 2 were synthesized over five steps using the methods of ref . In previous studies, , we used X-ray analysis to correlate the absolute configuration of ligand 2 to the absolute configuration of the product of a catalytic reaction. All CD measurements were performed using a JASCO J-815-150S CD spectrometer.…”