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. 2022 Aug 15;61(33):e202205516.
doi: 10.1002/anie.202205516. Epub 2022 Jun 9.

Zinc-Catalyzed Enantioselective [3+2] Cycloaddition of Azomethine Ylides Using Planar Chiral [2.2]Paracyclophane-Imidazoline N,O-ligands

Sundaravel Vivek Kumar  1 , Patrick J Guiry  1
Affiliations

Zinc-Catalyzed Enantioselective [3+2] Cycloaddition of Azomethine Ylides Using Planar Chiral [2.2]Paracyclophane-Imidazoline N,O-ligands

Sundaravel Vivek Kumar et al. Angew Chem Int Ed Engl. .

Abstract

We present a facile synthetic route toward a novel series of imidazolinyl-[2.2]paracyclophanol (UCD-Imphanol) ligands possessing central and planar chirality. Both sets of diastereomeric ligands were successfully purified by column chromatography. The preliminary application of this family of ligands showed excellent activities in the asymmetric Zn-catalyzed azomethine ylide cycloaddition. Enantioenriched pyrrolidines, in a substrate scope of 20 examples, were accessed in high levels of endo/exo ratios (up to >99/1) and enantioselectivities (up to >99 % ee) with excellent yields (up to 99 %) by using (S,S,SP )-UCD-Imphanol/(S,S,RP )-UCD-Imphanol, respectively.

Keywords: Asymmetric Catalysis; Cycloaddition; Cyclophanes; Planar Chiral; Zinc Catalysis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
[2.2]Paracyclophane‐derived ortho‐disubstituted ligands.
Scheme 1
Scheme 1
Synthesis and resolution of imidazolinyl‐[2.2]paracyclophanols (UCD‐Imphanols).
Scheme 2
Scheme 2
ZnII‐catalyzed asymmetric [3+2] azomethine ylide cycloaddition.
Scheme 3
Scheme 3
Substrate scope.[a–d] [a] Reaction conditions: 17 (0.225 mmol) 18 (0.15 mmol), Zn(OTf)2 (10 mol %), (S,S,S P)‐6  a/(S,S,R P)‐4  b (11.5 mol %), DABCO/DIPEA (10 mol %) in 1.0 mL of CH2Cl2, 28 h. [b] Isolated yield. [c] The endo/exo ratio was determined by 1H NMR spectroscopy of crude reaction mixture. [d] The ee was determined by chiral SFC analysis. [e] 1 mmol scale.
Scheme 4
Scheme 4
Synthetic transformations.
Scheme 5
Scheme 5
Proposed transition‐state model for ligands 6  a and 4  b.
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