Jump to main content
Jump to site search

Issue 21, 1994
Previous Article Next Article

[1N,3E]-bifunctional phosphorodiamidites and the diastereoselective phosphonylation of aldehydes. Controlling, elucidating and rationalising the stereochemical course of the asymmetric Abramov reaction

Abstract

The novel, chiral phosphorodiamidite [(1R,2S)-O,N-ephedrine]PN(SiMe3)22 has been prepared cleanly in both high chemical (83%) and epimeric (>98%) yields from the reaction of LiN(SiMe3)2 with [(1R,2S)-O,N-ephedrine]PCl 1. The configuration at phosphorus has been shown to be SP by a combination of NMR and derivatisation studies. Phosphorodiamidite 2 phosphonylates aldehydes (RCHO) readily via the Abramov reaction to afford α-siloxyimidophosphonate esters of the form [(1R,2S)-O,N-ephedrine]P(NSiMe3)CHR(OSiMe3)(R = alkyl and substituted phenyl) with diastereoselectivities up to 96%(for R = But). In each case, NMR spectroscopy reveals that both major and minor product esters have the Sp configuration supportive of the Abramov reaction proceeding with retention of configuration at phosphorus and this is supported by X-ray diffraction studies on α-siloxyimidophosphonate esters with R = 2-naphthyl 9 and 2-Ph2PC6H411. Subsequently, an empirical method of assigning configurations to both the phosphorus and α-carbon atoms is proposed on the basis of 1H and 31P NMR measurements. Experiments also suggest that the Abramov reaction (i) is subject to kinetic control under the conditions reported here but can be reversed under more forcing thermal conditions or in the presence of trace acid, (ii) involves intramolecular transfer of the triorganosilyl group, (iii) involves significant [P–C] bond formation in the rate-determining step, (iv) probably does not proceed via pre-coordination of the carbonyl oxygen atom to silicon (by 29Si{1H} NMR) in contrast to metallophosphite systems and (v) the configuration at the α-carbon stereocentre is controlled primarily by steric rather than distal electronic factors in systems where R = XC6H4. Consequently, steric interactions in the ratedetermining transition state may account for the reversal in face-selectivity in the reactions between compound 2 and 2-C10H7CHO, for which the major product isomer 9 has the (SP,SC) configuration, and 2 and 2-Ph2PC6H4CHO, for which the major product isomer 11 has the (SP,RC) configuration.

Back to tab navigation

Article type: Paper
DOI: 10.1039/P19940003183
J. Chem. Soc., Perkin Trans. 1, 1994, 3183-3200

  •   Request permissions

    [1N,3E]-bifunctional phosphorodiamidites and the diastereoselective phosphonylation of aldehydes. Controlling, elucidating and rationalising the stereochemical course of the asymmetric Abramov reaction

    V. Sum, C. A. Baird, T. P. Kee and M. Thornton-Pett, J. Chem. Soc., Perkin Trans. 1, 1994, 3183
    DOI: 10.1039/P19940003183

Search articles by author

Spotlight

Advertisements