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Issue 22, 1993
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Synthetic, stereochemical and mechanistic studies on the asymmetric phosphonylation of aldehydes via 2-triorganosiloxy-1,3,2-oxazaphospholidines

Abstract

The chiral 2-triorganosiloxy-1,3,2-oxazaphospholidines {(1R,2S)-ephedrine}POSiR3(R3= Ph34, ButMe25, Et36) have been prepared via the reactions of {(1R,2S)-ephedrine}PCl 1 with R3SiOH in the presence of NEt3. Each of these organophosphorus(III) esters exists as an equilibrium mixture of two epimers with a diastereoselectivity (d.s,) that is dependent upon the nature of the silicon substituents; R3= Et3[86.0(2)%], ButMe2[87.9(2)%], Ph3[94.1 (2)%]. The epimers do not interconvert readily on the NMR time-scale but do so slowly on the chemical reactivity time-scale, attesting to the relatively high configurational stability at phosphorus. All three 2-triorganosiloxy-1,3,2-oxazaphospholidines undergo the Abramov reaction with benzaldehyde and pivalaldehyde at room temperature to afford the α-triorganosiloxy phosphonate esters {(1R,2S)-ephedrine}P([double bond, length half m-dash]O)CHR′(OSiR3)(R′= Ph 1012, But1315) in high yields and with good stereoselectivities. In the best cases, with R′= Ph, a single isomer accounts for 76%(R3= Ph3), 67%(R3= ButMe2) and 73%(R3= Et3) respectively of the product mixtures, whereas with R′= But, the corresponding values are 61, 86 and 84% respectively. Evidence is presented to support the conclusion that the major product isomers of structures 1015 result from reaction of the aldehydes with the major epimers of compounds 46 with retention of configuration at phosphorus. The absolute configurations at the phosphorus and α-carbon atoms for the major isomer of {(1R,2S)-ephedrine}P([double bond, length half m-dash]O)CHBut(OSiPh3) have been assigned as (SP, Sc) by solution NOE experiments, which support a mechanism involving retention of configuration. The relative rates and stereoselectivities of the reactions of compounds 46 with carbonyls are sensitive to the nature of the substituents on both the silicon atom and the aldehyde. Reactions of compounds 46 with ketones are much slower than those with the aldehydes above, as expected on both electronic and steric grounds.

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Article type: Paper
DOI: 10.1039/P19930002701
J. Chem. Soc., Perkin Trans. 1, 1993, 2701-2711

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    Synthetic, stereochemical and mechanistic studies on the asymmetric phosphonylation of aldehydes via 2-triorganosiloxy-1,3,2-oxazaphospholidines

    V. Sum and T. P. Kee, J. Chem. Soc., Perkin Trans. 1, 1993, 2701
    DOI: 10.1039/P19930002701

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