Ana María Ochoa de Retana

2H-Azirines as Synthetic Tools in Organic Chemistry

The versatility and the high synthetic potential including the asymmetric syntheses of 2H-azirines as valuable precursors for the preparation of a wide range of polyfunctional acyclic and cyclic compounds, is discussed.

PREPARATION, PROPERTIES AND SYNTHETIC APPLICATIONS OF 2H-AZIRINES A REVIEW

INTRODUCTION .............................................................................................................................. 221 I . STRUCTURAL PROPERTIES OF W-AZIRLNES .................................................................. 222 1 . Molecular Orbital Calculations and Geometry ..................................................................... 222 2 . Spectroscopic Properties .......................................................................................................... 223 a) Nuclear Magnetic Resonance Spectroscopy ......................................................................... 223

Aza-Wittig reaction of N-phosphorylalkyl phosphazenes with carbonyl compounds and phenylisocyanate. Synthesis of 4-amino-3-phosphoryl-2-azadienes and pyrazine-phosphonates

Abstract Simple and functionalized N -phosphorylalkyl imines and N -phosphorylalkyl- N ′-phenyl-carbodiimides are obtained by aza-Wittig reaction of phosphazenes derived from aminophosphonates with carbonyl compounds and phenyl isocyanate. The reaction with dimethylformamide diethyl acetal (DMF–DEA) of these functionalized imines leads to the synthesis of 4-amino-3-phosphoryl-2-azadienes. N -Phosphorylmethyl imine derived from benzaldehyde can be used for the preparation of substituted pyrrole-phosphonates, while acid treatment of 4-dimethylamino-3-diethylphosphoryl-1-phenyl-2-azadiene gives diethyl 5-diethylphosphorylpyrazin-2-ylphosphonate.

Asymmetric synthesis of 2H-aziridine phosphonates, and α- or β-aminophosphonates from enantiomerically enriched 2H-azirines

Abstract A simple and efficient method for asymmetric synthesis of 2 H -azirine-2-phosphonates 6 is described. The key step is a base-mediated Neber reaction of p -toluenesulfonyloximes 4 derived from phosphonates. Triethylamine 5 , alkaloids 7 and solid-phase bound achiral 8 or chiral amines 9 are used. Reduction of 2 H -azirines 6 with sodium borohydride in ethanol gives cis -aziridine-phosphonates 10 . Ring opening of aziridines 10 and 11 leads to the formation of enantiomerically enriched β- 12 and 14 and α-aminophosphonates 13 and 15 .

Synthesis of optically active oxazoles from phosphorylated 2H-azirines and N-protected amino acids or peptides

A simple synthesis of optically active phosphorylated oxazoles 8, 10, 11, and 12 containing amino acid residues from 2H-azirine-phosphine oxides 1 or -phosphonates 6 is described. Ring-opening reaction of 2H-azirines derived from phosphine oxides 1 and phosphonates 6 with N-protected amino acids 2 gives functionalized phosphorylated ketamides 3 and 7. Cyclization of ketamides 3 and 7 with triphenylphosphine and hexachloroethane in the presence of triethylamine leads to the formation of racemic and optically active phosphorylated oxazoles containing N-protected amino acid residues 8 and 10. Deprotection of these oxazoles gives aminoalkyl oxazoles 11 and 12. 2H-Azirines 1 and 6 also react with N-protected peptides 13 and give functionalized ketamides 14 and 15, ring closure of which leads to the formation of phosphorylated oxazoles containing peptide residues 16 and 17.

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.