Application of Polyamines and Amino Acid Derivatives Based on 2-Azabicycloalkane Backbone in Enantioselective Aldol Reaction.

Dominika Iwan,Elżbieta Wojaczyńska,Karolina Kamińska

doi:10.3390/molecules26175166

Dominika Iwan, Elżbieta Wojaczyńska + Show 1 more

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https://doi.org/10.3390/molecules26175166

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Abstract

Carbon–carbon bond forming reactions, such as aldol reaction and condensation, belong to extremely desired transformations as manifested by >25,000 entries in SciFinder. Their stereoselective variant requires the use of an appropriate catalyst with a strictly defined structure. Hence, chiral 2-azabicycloalkane-based catalysts were designed, synthesized and tested in a stereoselective aldol reaction between cyclic/acyclic ketone and p-nitrobenzaldehyde both in organic and aqueous media. Among catalysts containing a chiral bicyclic backbone, amide based on 2-azabicyclo[3.2.1]octane and pyrrolidine units showed the best catalytic activity and afforded aldol product in excellent chemical yields (up to 95%) and good diastereo- and enantioselectivity (dr 22:78, ee up to 63%).

Highlights

IntroductionIntroduction of Polyamines and AminoDating back to the 19th century, the aldol reaction and its many variants remain an important tool used in organic synthesis for carbon–carbon bond formation and building up molecular complexity and diversity [1,2]
Dating back to the 19th century, the aldol reaction and its many variants remain an important tool used in organic synthesis for carbon–carbon bond formation and building up molecular complexity and diversity [1,2]
Structure modular chiral catalysts based onobtained pounds on of a 2-azanorbornane system were by appropriate modifications of the enantiomerically pure aza-Diels-Alder cycloadduct 1 (Scheme 1)

Summary

Introduction

Introduction of Polyamines and AminoDating back to the 19th century, the aldol reaction and its many variants remain an important tool used in organic synthesis for carbon–carbon bond formation and building up molecular complexity and diversity [1,2]. The attractive possibility of creation of two stereocenters in a single step led to the development of stereoselective versions of this transformation [3,4]. To this end, numerous efficient catalysts have been introduced, including chiral metal complexes and organocatalysts. Numerous efficient catalysts have been introduced, including chiral metal complexes and organocatalysts Among the latter, proline and its derivatives are worth mentioning. 1970s by two research groups (>90% enantiomeric excess was noted) [5–7]. Since this amino acid has been recognized as a versatile organocatalyst in a wide range of asymmetric transformations [8]. In spite of the continuous progress in the field, the existing systems have their drawbacks (e.g., limited substrate scope, access to a particular stereoisomer of the product), and further research is necessary

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