Asymmetric Synthesis of Functionalized Tetrasubstituted α-Aminophosphonates through Enantioselective Aza-Henry Reaction of Phosphorylated Ketimines

Vicario, Javier; Ortiz, Pablo; Ezpeleta, Jose Marı́a; Palacios, Francisco

doi:10.1021/jo502233m

Cited by 43 publications

(28 citation statements)

References 64 publications

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“…Therefore, in view of the demonstrated ability of phosphoric acids to catalyze the nucleophilic addition of pyruvate-derived enamines 4 to imines 5 , we thought that this activation could be extended to the enamines derived from dialkyl acetylenedicarboxylates. Consequently, continuing with the interest of our research group in the synthesis of nitrogenated heterocycles [33,34,35,36] and amino-acid derivatives [37,38,39,40], we report here the use of phosphoric acids as catalysts in a three-component reaction of amines, benzaldehyde, and diethyl acetylenedicarboxylate to afford densely functionalized γ-lactam derivatives.…”

Section: Introductionmentioning

confidence: 99%

A Brønsted Acid-Catalyzed Multicomponent Reaction for the Synthesis of Highly Functionalized γ-Lactam Derivatives

et al. 2019

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Brønsted acids catalyze a multicomponent reaction of benzaldehyde with amines and diethyl acetylenedicarboxylate to afford highly functionalized γ-lactam derivatives. The reaction consists of a Mannich reaction of an enamine to an imine, both generated in situ, promoted by a phosphoric acid catalyst and a subsequent intramolecular cyclization. The hydrolysis of the cyclic enamine substrate can provide enol derivatives and, moreover, a second attack of the amine on the carboxylate can afford amide derivatives. An optimization of the reaction conditions is presented in order to obtain selectively cyclic enamines that can afford the enol species after selective hydrolysis.

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Section: Introductionmentioning

confidence: 99%

A Brønsted Acid-Catalyzed Multicomponent Reaction for the Synthesis of Highly Functionalized γ-Lactam Derivatives

et al. 2019

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“…Short after that, the enantioselective addition of nitromethane to ketimines 53 was successfully performed, using 10 mol% of thiourea‐cinchona alkaloid XVIII as catalyst, to obtain α‐aminophosphonates 57 with yields and enantioselectivities above 80% (Scheme ).…”

Section: Enantioselective Reactions With α‐Iminophosphonatesmentioning

confidence: 99%

α‐Iminophosphonates: Useful Intermediates for Enantioselective Synthesis of α‐Aminophosphonates

et al. 2020

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A wide range of methods for the enantioselective synthesis of α‐aminophosphonic acid derivatives have been developed over the years. Although the most used methodology is the Pudovik reaction, the use of α‐iminophosphonates for the synthesis of optically active α‐aminophosphonates has emerged during the last years. The existing methods for the synthesis of α‐phosphorylated imines and their enantioselective reactions for the synthesis of enantio‐enriched α‐aminophosphonates are summarized in this review.

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“…communicated on excellent results in Pd‐catalyzed asymmetric hydrogenation of α ‐tosylimino phosphonates . However, the latter precursors cannot be considered the best choice, because they are synthesized from the same racemic α ‐tosylamino phosphonates by N ‐chlorination/dehydrochlorination procedure …”

Section: Figurementioning

confidence: 99%

“…[6] However, the latter precursors cannot be considered the best choice, because they are synthesized from the same racemic a-tosylamino phosphonates by N-chlorination/dehydrochlorination procedure. [7] Readily accessible a-oxo phosphonates [8] are important reagents for the preparation of elaborate phosphonates. Unfortunately, they cannot be used for the synthesis of the corresponding a-imino phosphonates since the interaction of simple nucleophiles like ammonia and amines as well as water, alcohols and thiols with a-oxo phosphonates leads to CÀP bond cleavage.…”

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confidence: 99%

One‐Pot Two‐Step Synthesis of Optically Active α‐Amino Phosphonates by Palladium‐Catalyzed Hydrogenation/Hydrogenolysis of α‐Hydrazono Phosphonates

et al. 2016

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An efficient and convenient one-pot procedure for the stereoselective catalytic synthesis of ring-substituted [amino(phenyl)methyl]phosphonates has been developed. The enantioselective hydrogenation of easily available diisopropyl (Z)-[aryl(phenylhydrazono)methyl]phosphonates using palladium(II) acetate as a precatalyst, (R)-2,2'-bis (diphenylphosphino)-5,5'-dichloro-6,6'-dimethoxy-1,1'-biphenyl [(R)-Cl-MeO-BIPHEP] as a ligand, and (1S)-(+)-10-camphorsulfonic acid as an activator in a mixture of 2,2,2-trifluoroethanol and methylene chloride at ambient temperature results in the formation of corresponding [aryl(2-phenylhydrazino)methyl]phosphonates. The subsequent cleavage of the NÀN bond has been accomplished with molecular hydrogen after the addition of palladium on carbon and methanol into crude reaction mixture to afford the optically active [amino(aryl)methyl]phosphonates. The method is operationally simple and provides an appreciable enantioselectivity up to 98 % ee.Keywords: a-amino phosphonates; asymmetric catalysis; a-hydrazono phosphonates; hydrogenation; palladium a-Amino phosphonates, particularly nonracemic ones, have been a topic for decades due to a wide spectrum of their possible applications.[1] Nevertheless, the stereocontrolled formation of a-amino phosphonates remains a challenge in chemical synthesis. Among catalytic concepts for the enantioselective synthesis of a-amino phosphonates, two methodologies are leading, namely, asymmetric hydrophosphonylation of aldimines and ketimines and asymmetric reduction of a,b-dehydroaminophosphonates.[2] Several years ago we reported on the feasibility of Rh-catalyzed asymmetric hydrogenation of a-imino phosphonates as a straightforward access to optically active a-amino phosphonates containing the quaternary b-carbon atom.[3] Subsequently, this approach was extended on oxazaborolidine catalyzed reduction of (2,2,2-trifluoro-1-iminoethyl)phosphonates with catecholeborane.[4] Along with all apparent advantages, some pitfalls of this method should be mentioned. First, aimino phosphonates are actually an equilibrium mixture of Z/E-isomers, which may have an adverse effect on the overall stereoselectivity of the process. In addition, these starting substrates are slowly hydrolyzed on storage. Finally, the common synthesis of aimino phosphonates via the Michaelis-Arbuzov rearrangement requires the usage of labile imidoyl chlorides under harsh reaction conditions.[5] When the present paper was in preparation, Zhou et al. communicated on excellent results in Pd-catalyzed asymmetric hydrogenation of a-tosylimino phosphonates. [6] However, the latter precursors cannot be considered the best choice, because they are synthesized from the same racemic a-tosylamino phosphonates by N-chlorination/dehydrochlorination procedure. [7] Readily accessible a-oxo phosphonates [8] are important reagents for the preparation of elaborate phosphonates. Unfortunately, they cannot be used for the synthesis of the corresponding a-imino phosphonates since the interaction of si...

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Asymmetric Synthesis of Functionalized Tetrasubstituted α-Aminophosphonates through Enantioselective Aza-Henry Reaction of Phosphorylated Ketimines

Cited by 43 publications

References 64 publications

A Brønsted Acid-Catalyzed Multicomponent Reaction for the Synthesis of Highly Functionalized γ-Lactam Derivatives

A Brønsted Acid-Catalyzed Multicomponent Reaction for the Synthesis of Highly Functionalized γ-Lactam Derivatives

α‐Iminophosphonates: Useful Intermediates for Enantioselective Synthesis of α‐Aminophosphonates

One‐Pot Two‐Step Synthesis of Optically Active α‐Amino Phosphonates by Palladium‐Catalyzed Hydrogenation/Hydrogenolysis of α‐Hydrazono Phosphonates

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