Planar‐ and Central‐Chiral N,O‐[2.2]Paracyclophane Ligands: Non‐Linear‐Like Effects and Activity

Abstract

The non-linear-like effect (NLLE), activity, temperature dependence, and kinetics of hydroxy-[2.2]paracyclophane ketimine ligands have been investigated with the 1,2-addition reaction of diethylzinc to cyclohexanecarbaldehyde. A linear correlation between the enantiomeric excess of AHPC ketimine ligands bearing a phenylethyl side group and the product was observed with 0.5 mol % of catalyst loading. On increasing the catalyst loading to 4 mol %, a precipitate of the inactive heterochiral species was formed and resulted in a positive nonlinear-like effect. The enantiomeric ratio was found to have linear temperature dependence.Keywords: asymmetric catalysis; catalytic activity; non-linear-like effect; paracyclophanes Asymmetric catalysis often displays a relationship between selectivity and reactivity. Intricate molecular mechanisms with a number of rate constants often lead to complex rate laws. The latter have not been elucidated in most cases although attempts have been made to unravel them.[1] Features such as non-linear effects, [2] autocatalysis, [3] reservoir effects, chiral poisoning, [4] and asymmetric activation [5] have been discovered in asymmetric catalytic reactions.[6] In particular, the strong non-linear effect associated with Noyoris DAIB ligand in the addition of diethylzinc to benzaldehyde has been thoroughly investigated.[7a]Since the initial reports of Reich and Cram, [8] the field of [2.2]paracyclophane chemistry has grown considerably.[9] The chemical behavior of [2.2]paracyclophanes is currently well understood allowing predictable modification of this relatively stable class of molecules. [10 -13] Within the last few years, various new paracyclophane ligands have been used for asymmetric catalysis. [14 -17] In particular, the asymmetric 1,2-addition reaction of zinc reagents [18] such as alkyl, [19 -21] alkenyl, [22] aryl [23] and alkynyl [24] zinc reagents with aldehydes or imines, [19,20,23] can be efficiently controlled by the application of hydroxy[2.2]paracyclophane ketimine ligands.[17]We recently reported the synthesis of the [2.2]paracyclophane-based ketimine ligands (R P ,S)-2, (S P ,S)-2, (R P ,S)-3, and (S P ,S)-3 and their application in asymmetric catalysis such as the addition of zinc reagents to aldehydes. [19] During these studies, we observed not only that these ligands are highly active, [21,25] but also that they display mismatched and matched cases. [19,22] In general, the [2.2]paracyclophane backbone determines the configuration of the product. However, it was possible to finetune the ligand system by adjusting the side groups.The successful applications of these [2.2]paracyclophane-based ligands led to further investigations of this system. In this manuscript, we disclose our findings which lead to a deeper understanding of this ligand class. We present studies of the non-linear-like effect (NLLE) [26] with the enantiomeric pairs 1 and 3, respectively. In addition, we investigated the activity of the diastereomers (R P ,S)-2 and (S P ,S)-2 and the diaste...

Synthesis and application of chiral β‐amino disulfides as ligands for the enantioselective addition of diethylzinc to aldehydes

“…At this point, it has to be mentioned that the described ligand systems display a high reactivity compared to most of the other ligand systems described in the literature. 73,74 In addition, we investigated the temperature effect on the enantiomeric excess of the product in the same (1,2)-addition reaction. We also observed that this process is sensible to this effect, in terms of yield and selectivity.…”

[2.2]Paracyclophane Derivatives: Synthesis and Application in Catalysis

“…44 Accordingly, an NLE was observed for (R P ,R)/(S P ,S)-50 and (R P ,R)/(S P ,S)-54 in the 1,2-addition of diethylzinc (53) to cyclohexyl aldehyde. 45 For the ligand 50 a positive correlation was observed, and was attributed to the precipitation of a less soluble heterodimer from solution. This was underpinned by the fact that a linear correlation was observed at lower catalyst concentrations.…”

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

“…[29] Use in Asymmetric Addition of Diethylzinc to Benzaldehyde Several [2.2]paracyclophane N,O ligands have been described in the literature. As well as those derived from FHPC, mentioned in the introduction, many similar ketimines and amines have been synthesized and used for the diorganozinc addition to aldehydes [30][31][32][33][34] and imines. [35] Of closest analogy to our compounds, are the pseudo-geminal dimethyl-/diphenylhydroxymethyl-oxazolinylA C H T U N G T R E N N U N G [2.2]paracyclophanes developed by Hou, which led to ees of up to 98 % when used as ligands in the addition of diethylzinc to benzaldehyde.…”