[1(N),3(E)]-BIFUNCTIONAL PHOSPHORODIAMIDITES AND THE DIASTEREOSELECTIVE PHOSPHONYLATION OF ALDEHYDES - CONTROLLING, ELUCIDATING AND RATIONALIZING THE STEREOCHEMICAL COURSE OF THE ASYMMETRIC ABRAMOV REACTION

The novel, chiral phosphorodiamidite [(1R,2S)-O,N-ephedrine]PN(SiMe(3) )(2) 2 has been prepared cleanly in both high chemical (83%) and epime ric(>98%) yields from the reaction of LiN(SiMe(3))(2) with [(1R,2S)-O, N-ephedrine]PCl 1. The configuration at phosphorus has been shown to b e S-p by a combination of NMR and derivatisation studies. Phosphorodia midite 2 phosophonylates aldehydes (RCHO) readily via the Abramov reac tion to afford alpha-siloxyimidophosphonate ester of the form [(1R,2S) -O,N-ephedrine]P(NSiMe(3))CHR(OSiMe(3)) (R = alkyl and substituted phe nyl) with diastereoselectivities up to 96% (for R = Bu(t)). In each ca se, NMR spectroscopy revels that both major and minor product esters h ave the S-p configuration supportive of the Abramov reaction proceedin g with retention of configuration at phosphorus and this is supported by X-ray diffraction studies on alpha-siloxyimidophosphonate esters wi th R = 2-naphthyl 9 and 2-Ph(2)PC(6)H(4) 11. Subsequently, an empirica l method of assigning configurations to both the phosphorus and alpha- carbon atoms is proposed on the basis of H-1 and P-31 NMR measurements . Experiments also suggest that the Abramov reaction (i) is the subjec t to kinetic control under the conditions reported here but can be rev ersed under more forcing thermal conditions or in the presence of trac e acid, (ii) involves intramolecular transfer of the triorganosilyl gr oup, (iii) involves significant [P-C] bond formation in the rate-deter mining step, (iv) probably does not proceed via pre-coordination of th e carbonyl oxygen atom to silicon (by Si-29{H-1} NMR) in contrast to m etallophosphite systems and (v) the configuration at the alpha-carbon stereocentre is controlled primarily by steric rather than distal elec tronic factors in systems where R=XC(6)H(4). Consequently, steric inte ractions in the rate-determining 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 (S-p,S-c) conf iguration, and 2 and 2-Ph(2)PC(6)H(4)CHO, for which the major product isomer 11 has the (S-p,R(c)) configuration