Chiral Bis(Imidazolidine)Pyridine-Cu Complex-Catalyzed Enantioselective [3+2]-Cycloaddition of Azomethine Imines with Propiolates

Takayoshi Arai,Yuta Ogino

doi:10.3390/molecules17056170

Takayoshi Arai, Yuta Ogino

Open Access

https://doi.org/10.3390/molecules17056170

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Journal: Molecules (Basel, Switzerland)	Publication Date: May 24, 2012
Citations: 77	License type: CC BY 4.0

Affiliation: Chiba University

Abstract

[3+2] Cycloaddition of azomethine imines with electron-deficient terminal alkynes was smoothly catalyzed by a chiral bis(imidazolidine)pyridine-CuOAc complex to give bicyclic pyrazolo[1,2-a]pyrazolone derivatives with up to 74% ee.

Highlights

Functionalized complex molecules are key tools for promoting biochemical research and developing pharmaceuticals, because the network of chiralities, the positions of heteroatoms, and the direction of lone-pairs in the molecules correlate strictly with their biological activities
The unique pyrazolone heterocycles, five-membered-ring lactams containing N-N conjunction, are examples of highly functionalized complex molecules, which have been used for the development of fine chemicals and the pharmaceuticals (Figure 1) [1,2,3]
LY173013 and LY186826 are the Molecules 2012, 17 representative examples of antibacterial agents, which have been developed as the analogues of penicillin and cephalosporin antibiotics [10,11,12,13,14]

Summary

Introduction

Functionalized complex molecules are key tools for promoting biochemical research and developing pharmaceuticals, because the network of chiralities, the positions of heteroatoms, and the direction of lone-pairs in the molecules correlate strictly with their biological activities. For accessing the fascinating bicyclic pyrazolo[1,2-a]pyrazolone skeleton, the [3+2] cycloaddition of azomethine imines has apparent advantage for the straightforward construction of the core structure (Scheme 1) [15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. In 2010 we succeeded in the development of bis(imidazolidine)pyridine, abbreviated as PyBidine, for the catalytic asymmetric [3+2] cycloaddition of iminoesters with nitroalkene (Scheme 2) [37]. We envisioned that the new chiral PyBidine ligand would have wide potential to promote various asymmetric reactions, and the [3+2] cycloaddition using azomethine imines was set to study for constructing the fascinating bicyclic pyrazolo[1,2-a]pyrazolones in this report. Asymmetric [3+2] cycloaddition catalyzed by PyBidine-Cu(OTf) complex

Results and Discussion

General

General Procedure

Conclusions