Organocatalytic Cascade Reaction of Aliphatic Enals and Benzoylnitromethane: Synthesis of Enantioenriched Tetrasubstituted Cyclohexene Carbaldehyde

Fredy A David Rodriguez,James Guevara-Pulido,Mauricio Maldonado Villamil

doi:10.1155/2020/9248793

Fredy A David Rodriguez, James Guevara-Pulido + Show 1 more

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https://doi.org/10.1155/2020/9248793

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Abstract

A new example of the reactivity of enals with benzoylnitromethane was studied in a Michael-Michael-Aldol-Dehydration quadruple organocascade reaction. The reaction unexpectedly yielded a tetrasubstituted cyclohexene carbaldehyde with excellent enantiomeric excess when crotonaldehyde was used as the Michael-acceptor, whereas using (E)-Hex-2-enal as the Michael-acceptor formed a cyclic hemiacetal by steering the reaction into the intramolecular formation of the same intermediate via a Michael-Heterocyclization domino reaction.

Highlights

Organocascade reactions have played an important role in the efficient production of highly complex chemical structures [1, 23]
Organocatalysis and the influence of the pKa of benzoylnitromethane were evaluated in the reaction with crotonaldehyde and (E)-Hex-2-enal as starting reactants for the formation of Michael adducts and their subsequent intramolecular cyclization, promoting the formation of cycles with consecutive stereocenters, which can be used as building blocks for more complex molecules. e results showed that in addition to pKa, the length of the alkyl chain of the unsaturated aldehyde is decisive for the type of cyclic system that can be obtained. e reaction conditions of the process were studied and demonstrated that the reaction time is decisive in the formation of adducts
Crotonaldehyde and (E) Hex-2-enal were used as Michael-acceptor while (A) (R)—(+)—α, α-diphenyl-2pyrrolidinemethanol trimethylsilyl ether and (B) proline were used as catalysts, where the latter served as a bifunctional catalyst activating both enals and nitroketones

Summary

Introduction

Organocascade reactions have played an important role in the efficient production of highly complex chemical structures [1, 23]. An interesting example is the formation of Michael adducts and their subsequent intramolecular cyclization, promoting the formation of cycles with consecutive stereocenters, which can be used as Journal of Chemistry building blocks for more complex molecules In this way, the influence of the pKa [36,37,38,39,40] of (pronucleophiles) is decisive in obtaining the type of product. Organocatalysis and the influence of the pKa of benzoylnitromethane (pronucleophile) were evaluated in the reaction with crotonaldehyde and (E)-Hex-2-enal as starting reactants for the formation of Michael adducts and their subsequent intramolecular cyclization, promoting the formation of cycles with consecutive stereocenters, which can be used as building blocks for more complex molecules. Organocatalysis and the influence of the pKa of benzoylnitromethane (pronucleophile) were evaluated in the reaction with crotonaldehyde and (E)-Hex-2-enal as starting reactants for the formation of Michael adducts and their subsequent intramolecular cyclization, promoting the formation of cycles with consecutive stereocenters, which can be used as building blocks for more complex molecules. e results showed that in addition to pKa, the length of the alkyl chain of the unsaturated aldehyde is decisive for the type of cyclic system that can be obtained. e reaction conditions of the process were studied and demonstrated that the reaction time is decisive in the formation of adducts

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Conclusion