Modern Asymmetric Organocatalysts for 1,3-dipolar Cycloaddition Reaction- Review Article

Introduction

In the Year 2000, MacMillan and co-workers are discovering a new asymmetric organocatalyst iminium ion with chiral imidazolidinones. Using the concept LUMO lowering to strong reaction activity of α, β-unsaturated aldehyde/ketone which is the reaction with 1,3-dipole nitrones. 

Created by Chemarticle: Modern Asymmetric Organocatalysts for 1,3-dipolar Cycloaddition Reaction

A few years later 2006, published an article on the triflate salt (the treatment of diphenyl-s-proline with trimethylsilyl triflate), the catalyst addition, or 1,3-dipolar cycloaddition of nitrones to α, β-unsaturated aldehyde to the formation of isoxazolidines with high production yield and good diastereoselective and enantioselective product. 

In the case that decided the [3+2] cycloaddition reaction between nitrones and α, β-unsaturated aldehyde, we are just using the most commercially available and low-cost starting materials. Now we have to consider the commercially available Catalyst for cycloaddition of N-bezylidenebenzylamine N-oxide and crotonaldehyde. The list of asymmetric organocatalysts (in case use of a variety of amine catalysts) whole enter cycloaddition reaction of N-benzylidenebenzylamine N-oxide with (E)-aldehyde.

In case use the solvent CH₂Cl₂-IPA (85:15) at 4℃ temperatures. We can see the table of the amine catalysts – 1c catalysts are most sensitive under the whole condition. 

various types of asymmetric amine catalysts.

Professor David MacMillan use the catalysts – the catalysts 1e (that is known as second-generation MacMillan catalysts), in case solvent corresponded to fever toluene -optimized the reaction rate, Di-stereoselectivity, enantioselectivity products.

Added the new things to more advanced fractures organocatalyzed compared to MacMillan catalysts. That causes in 2006 San San Chow, Marta Nevalainen, and co-worker discovered a new organo-catalysts- which is similar to MacMillan organocatalysis. See in the table -1c the organo-catalysts new has more %ee value (96%, time taken 3 days, the presents of major and minor product 93:7) compared to other catalysts.

Advantage of modern Organocatalyst

Compound 1c catalysts have more advanced compared to 1e (MacMillan catalysts). The advances of 1c catalysts are easy to prepare from commercially available diphenyl-S-prolinol with a one-step reaction, on the other hand, the MacMillan catalysts 1e required multiple step’s reaction from phenylalanine methyl ester.

And remaining all catalysts (1a, 1b, 1d, and 1f molecular structure) are carried lower enantioselectivities in the [3+2] cycloaddition reaction.

Now we have to consider the cycloaddition reaction of α, β-unsaturated aldehyde, and nitrones. The scope of interaction between α, β-unmatured aldehyde, and various nitrones catalysts with 1c organo-catalysts.

(a) Cycloaddition reaction between alpha, beta-unsaturated aldehyde, and nitrones in presence of 1c catalyst. (b) Cycloaddition reaction between cyclopentene carboxaldehyde and nitrones in presence of 1c catalyst.  

In case [3+2] cycloaddition reaction, the N-alkyl group (that is Z=Bn, Me) is more affordable produced the produced, which is a more enantioselective character like 95% and 94 % respectively.

The exclusive enantioselective produced formation of the endo- structure (endo-(4s)-isoxazolidine), which is briefly involved in optically rotatable organocatalysis 1c.

Better help to formation of iminium ion, the using of 1c catalysts. It the difficulted to choose the potion of the catalysts to the formation of PM3- Structure (iminium ion). In the case of 1c catalysts, the phenyl groups are effectively shielded that why the Re-face of dipolarophile is corresponded to shield. That is why the cycloaddition proceeds in the Si- face of the nitrone.

Iminium ion formation from 1c catalyst and acrolein.

Summary:

Modern chiral pyrrolidine derivative, synthesized using one-step reaction to form organocatalyzed, and most important the starting materials are commercially available. Now, this organocatalysis is used to asymmetric (3+2) cycloaddition reaction. 

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