Structural and stereogenic properties of spiro- and ansa-substituted 1,3-propanedioxy derivatives of a spermine-bridged cyclotriphosphazene

Abstract

Reaction of 1,3-propanediol with the achiral spermine-bridged cyclophosphazene 1 at various molar ratios in THF gives a number of spiro-and ansa-derivatives that exhibit different stereogenic properties, viz. racemic, meso or achiral forms. As expected, spiro forms are preferred (giving mono-, di-, tri- and tetra-substitution), although significant amounts of mono- and di-substituted ansa derivatives also occur. A number of new structures have been characterized by NMR spectroscopy and X-ray crystallography in this work; mono-spiro 2, di-mono-ansa 6 and di-spiro/mono-ansa 8. The mono-ansa compound 3 was observed in solution by NMR spectroscopy but no evidence was found for the monospiro/monoansa 5, a necessary precursor of compound 8. The tri-spiro derivative 7 has been isolated and characterized by P-31 NMR spectroscopy, whereas the structures of the di-monospiro 4 (meso) and tetra-spiro 9 have been characterized previously. The stereogenic properties of many of the products have been confirmed by X-ray crystallography and/or by P-31 NMR spectroscopy on addition of the chiral solvating agent, (S)-(+)-2,2,2-trifluoro-1-(9-anthryl)ethanol. Although the starting compound I is achiral, it is found that unsymmetrically-substituted derivatives with 1,3-propanediol give racemic mixtures for the mono-spiro 2 and tri-spiro 7 derivatives, whereas symmetrically-substituted derivatives such as di-mono-ansa 6 and di-spiro/mono-ansa 8 are meso. It is found that care must taken in interpreting the 'splitting' of P-31 NMR signals on addition of CSA in terms of 'chirality' of molecules, because some meso compounds give false positive results due to changes from A(2)X-like to A(2)B or ABX spin systems. (c) 2005 Elsevier Ltd. All rights reserved.