Chiral phosphinyl analogues of 2-C-arylmorpholinols: 2-aryl-3,5-diphenyl-[1,4,2]-oxazaphosphinanes

(2R,3R,5R)-2-Aryl-3,5-diphenyl-[1,4,2]-oxazaphosphinanes 6, analogues of C-arylmorpholinol 3, were prepared with diastereomeric excess higher than 94%, via a three step sequence: (i) diastereoselective addition–cyclization reaction from methyl hypophosphite and a chiral imine 10, (ii) pallado-catalyzed arylation, and then (iii) a selective inversion of configuration at the phosphorus center.

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(2S,3R,5R)-(−)-3,5-Diphenyl-2-hydrogeno-2-oxo-[1,4,2]-oxazaphosphinaneC15H16NO2P[α]D20=-19.0 (c 1.04, CHCl3)

(2S,3R,5R)-(+)-2,3,5-Triphenyl-2-oxo-[1,4,2]-oxazaphosphinaneC21H20NO2P[α]D20=+140.3 (c 0.52, CHCl3)

(2S,3R,5R)-(+)-2-p-Methoxyphenyl-3,5-diphenyl-2-oxo-[1,4,2]-oxazaphosphinaneC22H22NO3P[α]D20=+145.6 (c 0.51, CHCl3)

(2S,3R,5R)-(+)-2-p-Bromophenyl-3,5-diphenyl-2-oxo-[1,4,2]-oxazaphosphinaneC21H19BrNO2P[α]D20=+160.8 (c 0.51, CHCl3)

(2S,3R,5R)-(+)-2-m-Chlorophenyl-3,5-diphenyl-2-oxo-[1,4,2]-oxazaphosphinaneC21H19ClNO2P[α]D20=+152.7 (c 0.55, CHCl3)

(2S,3R,5R)-(+)-2-(3,5-Difluorophenyl)-3,5-diphenyl-2-oxo-[1,4,2]-oxazaphosphinaneC21H18F2NO2P[α]D20=+122.2 (c 0.54, CHCl3)

(2R,3R,5R)-(−)-2,3,5-Triphenyl-2-oxo-[1,4,2]-oxazaphosphinaneC21H20NO2P[α]D20=-91.7 (c 0.48, CHCl3)

(2R,3R,5R)-(−)-2-(3,5-Difluorophenyl)-3,5-diphenyl-2-oxo-[1,4,2]-oxazaphosphinaneC21H18F2NO2P[α]D20=-80.0 (c 0.50, acetone)