Gloria Rubiales

Synthetic Applications of Intramolecular Aza-Wittig Reaction for the Preparation of Heterocyclic Compounds

A review focused on recent advances in intramolecular aza-Wittig reaction of phosphazenes with several car- bonyl or analogous compounds is reported. Phosphazenes afford intramolecular aza-Wittig reaction with different groups within the molecule as aldehydes, ketones, esters, thioesters, amides, anhydrides and sulfimides. One of the most impor- tant applications of this reaction is the synthesis of a wide range of heterocyclic compounds, ranging from simple mono- cyclic compounds to complex polycyclic and macrocyclic systems.

A new and efficient synthesis of imidazo[1,5-a] pyridine derivatives by a tandem aza-Wittig / electrocyclic ring closure of N-vinylic phosphazenes

Abstract Imidazo[1,5-a]pyridines 1 are prepared by reaction of N -vinylic phosphazene 3 , obtained from phosphorus ylide 5 and 2-cyanopyridine 4 , with aldehydes. Formation of fused heterocycles 1 can be explained through aza-Wittig reaction of phosphazene 3 , followed by 1,5-electrocyclic ring closure of the resulting aldimines 2 . Phosphazene 3 undergoes pyrido annelation by reaction with Diethyl Ketomalonate to give isoquinoline derivative 9 .

Aza-Wittig reaction of N-vinylic phosphazenes with carbonyl compounds. Azadiene-mediated synthesis of dihydropyridines and pyridines

Abstract Aza-Wittig reaction of N -vinylic phosphazenes derived from diphenylmethylphosphine 4 with carbonyl compounds leads to the formation of 2-azadienes derived from β-aminoacids 5 . Dimerization of 2-azadienes 5c,d and reaction of compounds 5 with phosphazene 4 or enemine 6 affords substituted dihydropyridines 7 and 8 . Aza-Wittig reaction of phosphazenes 4 with α,β-unsaturated aldehydes gives 3-azatrienes 12 , which are easily converted into pyridines 13 .

Synthetic utility of azetidine-2,3-diones: a new approach to 3-hydroxyethylβ-lactams and α-aminoacid derivatives

Abstract Baeyer-Villiger oxidation of azetidine-2,3-diones provides a new route to α-aminoacid-N-carboxyanhydrides. Conversion of azetidine-2,3-diones into 3-acetyl-β-lactams is also described.

Synthesis of fluorinated β-aminophosphonates and γ-lactams.

The functionalized polyfluorophosphorylated 1-azadienes I have been prepared by a Wittig reaction of ethyl glyoxalate and perfluorophosphorylated conjugated phosphoranes, obtained by reaction of phosphazenes and fluorinated acetylenic phosphonates. Subsequent reduction of both carbon-carbon and carbon-nitrogen double bonds of these 1-azadienes I affords the fluorine-containing β-aminophosphonates II, with the syn β-aminophosphonate being obtained as the major diastereoisomer. Base-mediated cyclocondensation of a diastereomeric mixture of aminophosphonates II leads exclusively to a new type of functionalized trans-γ-lactams III in a diastereoselective way. A computational study has also been used to explain the observed diastereoselectivity of these reactions.

Cycloaddition Reactions of Neutral 2‐Azadienes with Enamines − Regiospecific Synthesis of Highly Substituted Dihydropyridines and Pyridines

The reaction between electronically neutral 2-azadienes and enamines affords isoquinolines, bicyclic pyridine derivatives, tetrasubstituted 1,2-dihydropyridines, and pyridines. Dimerization of heterodienes gives pentasubstituted 2,3-dihydropyridines and pyridines in a regioselective fashion.

Preparation and reactivity of electron-poor 2-azadienes. Diels-Alder reaction with trans-cyclooctene.

Abstract Di-, tri- and tetra- substituted 2-azadienes 3 with electron withdrawing groups have been obtained by Aza-Wittig reaction of N -vinylic phosphazenes with carbonyl compounds. The Diels-Alder reaction of 3 with trans -cyclooctene has also been explored.

Hetero-Diels-Alder reaction of phosphinyl and phosphonyl nitroso alkenes with conjugated dienes: an aza-Cope rearrangement.

Phosphorylated nitroso alkenes react with cyclic dienes such as cyclopentadiene or cyclohexadiene to afford hetero Diels-Alder-type cycloadducts where the nitroso alkene participates as dienophile component and the cyclic olefin acts as the 4π-electron (diene) system. Subsequent aza-Cope rearrangement affords highly functionalized 5,6-dihydro-4H-1,2-oxazines. Conversely, the reaction of TMS-substituted cyclopentadiene (dienophile) with nitroso alkenes as heterodienes leads directly to bicyclic 1,2-oxazines. Theoretical studies are in agreement with the experimental results and with the new aza-Cope rearrangement proposed.

Reaction of acetylenic esters and N-functionalized phosphazenes. 1,2- versus 1,4-addition of N-vinylic phosphazenes

Reaction of phosphazenes derived from aminophosphonates with acetylenic esters leads to conjugated phosphorus ylides. The formation of these stabilized ylides is explained through a [2 + 2] cycloaddition reaction of the P = N linkage of the phosphazene (1,2-addition) and the triple bond of the acetylenic ester followed by ring opening of the azaphosphete intermediate. However, in the case of N-vinylic phosphazenes, the phosphazenes derived from triphenyl- and trimethyl-phosphine react as enamines (1,4-addition) with diacetylenic esters, whereas in phosphazenes derived from trimethylphosphine a 1,2-addition of ethyl propiolate to the P = N linkage of the phosphazene is produced.

A β-lactam approach to ψ-amino-β-keto acid derivatives.

Abstract Formation of ψ-amino-β-keto acid derivatives by enolate acylation with N-carboxyanhydrides previously formed from α-keto β-lactams is described.