Javier Vicario

Regioselective alkylation reactions of hydrazones derived from phosphine oxides and phosphonates. Synthesis of phosphorus substituted 1-amino-pyrrolones, pyridinones and pyrroles

Abstract Functionalized hydrazones derived from phosphine oxides or phosphonates were obtained from azaenolates of hydrazones and alkyl halides. The regioselectivity of alkylation of α-phosphorylated hydrazones can be controlled by phosphorus moiety. α-Alkylated compounds were used for the synthesis of heterocycles such as 1-aminopyrrol-2-ones, 1-amino-3,4-dihydropyridin-2-ones and 1-aminopyrroles containing phosphinyl or phosphoryl substituents.

Conjugate Addition of Amines to an α,β-Unsaturated Imine Derived from α-Aminophosphonate. Synthesis of γ-Amino-α-dehydroaminophosphonates

Aza-Michael reaction of ammonia, aliphatic, aromatic and optically active amines to an alpha,beta-unsaturated imine derived from alpha-aminophosphonate affords alpha-dehydroaminophosphonates with a gamma-stereogenic center bearing an amino group. Resulting gamma-amino alpha-dehydroaminophosphonates can be used for the preparation of phosphorylated pyrimidine derivatives.

Synthesis of Quinolinylphosphane Oxides and -phosphonates from N-Arylimines Derived from Phosphane Oxides and Phosphonates

Quinolinylphosphane oxides are obtained by thermal treatment of N-arylimines derived from phosphane oxides with dimethylformamide diethyl acetal (DMF-DEA). An intermediate N-aryl-1-azadiene was isolated and cyclization thereof leads to phosphorylated quinolines. In a similar manner, quinolinylphosphonates are obtained by reaction of N-arylimines derived from phosphonates with DMF-DEA. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2002)

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

Bifunctional Cinchona alkaloid thioureas efficiently catalyze asymmetric nucleophilic addition of nitromethane to ketimines derived from α-aminophosphonic acids to afford tetrasubstituted α-amino-β-nitro-phosphonates. Catalytic hydrogenation of (S)-α-amino-β-nitro-phosphonate 2d gives enantiopure (S)-α,β-diaminophosphonate 3.

Regioselective Alkylation Reactions of Enamines Derived from Phosphane Oxides − Synthesis of Phosphorus Substituted Enamino Esters, δ‐Amino‐phosphonates, Pyridone Derivatives and Pyrroles

α-Substituted (2-iminoalkyl)phosphane oxides were obtained from the azaenolates of imines or enamines and alkyl halides. The functionalized imines or enamines thus obtained were used for the synthesis of δ-amino esters, δ-amino phosphonates and heterocycles such as 3,4-dihydropyridin-2-ones, 2-pyridones and pyrroles containing a phosphinyl substituent.

α-Ketiminophosphonates: Synthesis and Applications

Abstract The synthesis of α-iminophosphonates derived from ketones has been achieved by aza-Wittig reaction of P-trimethylphosphazenes with acylphosphonates. These unstable compounds can be used for the synthesis of chiral α-aminophosphonate derivatives through addition of nucleophiles to the C-N iminic double bond. Moreover, if α,β-unsaturated imines are used, regioselective Michael addition to the conjugated bond yields α-dehydroamino-phosphonic acid derivatives functionalized at the γ-position.

Selective 1,2-vs 1,4-addition of n-arylphosphazenes to β,γ-unsaturated α-ketoesters. synthesis of quinolinecarboxylates

Selective conjugate reaction (1,4-addition) of N-arylphosphazenes derived from triphenylphosphine to α,β-unsaturated carbonyl compounds yielded 2-quinolinecarboxylates. However, when more reactive phosphazene species derived from trimethylphosphine were used, selective reaction with the carbonyl carbon (1,2-addition) occurred and N-aryl-1-azadienes were obtained. Thermal 6π-azaelectrocyclization of these 1-azadienes afforded 4-quinolinecarboxylates.

Brönsted-Acid-Catalyzed Asymmetric Three-Component Reaction of Amines, Aldehydes, and Pyruvate Derivatives. Enantioselective Synthesis of Highly Functionalized γ-Lactam Derivatives

Chiral phosphoric acids are efficient organocatalysts for the asymmetric three-component reaction of amines, aldehydes, and pyruvate derivatives. Simultaneous condensation of amines with both carbonylic compounds followed by a hydrogen bonding activated nucleophilic addition of enamines to imines affords densely functionalized enantioenriched 1,5-dihydro-2H-pyrrol-2-ones. These substrates can be used in subsequent diastereoselective transformations to afford enantiopure γ-lactam derivatives.

β-Hydroxyimino Phosphorus Derivatives. An Efficient Tool in Organic Synthesis

The purpose of this review article is to illustrate synthetic aspects of functionalized phosphorus derivatives containing an oximo moiety at the beta-position. First section will be focused on the synthesis of phosphine oxides, phosphonates or phosphonium salts containing an oxime group. The synthesis of these derivatives comprises the carbon-phosphorus single bond construction by reaction of haloximes with phosphorus derivatives, nucleophilic addition of phosphorus reagents to carbonyl compounds, or nucleophilic addition of phosphorus reagents to nitro olefins. This section will also concentrate on the most practical routes for the synthesis of the target com- pounds, through carbon-nitrogen double bond formation, which are as follows: condensation processes of carbonyl compounds and hy- droxylamine derivatives or addition of hydroxylamines to allenes or alkynes. The preparative use of beta-oximo phosphorus derivatives as synthetic intermediates will be discussed in a second section, comprising olefination reaction, oxidation of oximes to nitrile oxides by reaction at the C-N double bond of the oxime moiety, oxidation of these substrates to nitrosoalkenes, reduction to the corresponding hy- droxylamines and some reactions at the hydroxyl group of the hydroxyimino moiety.

Synthesis of novel antiproliferative hybrid bis-(3-indolyl)methane phosphonate derivatives

An efficient synthetic methodology for the preparation of phosphorus substituted bis-(3-indolyl)methane through a double nucleophilic addition of indole derivatives to an in situ generated α-iminophosphonate is reported. In addition, bis-(3-indolyl)methane substrates showed inxa0vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines A549 (carcinomic human alveolar basal epithelial cell) and SKOV03 (human ovarian carcinoma).