Grignard addition to aldonitrones. Stereochemical aspects and application to the synthesis of C-2-symmetric diamino alcohols and diamino diols

A new example of the stereoselective installation of the amino group at a s aturated carbon center via organometallic addition of chiral aldehydes to n itrones is illustrated by the synthesis of 1,3-diamino propanol 1 and 1,4-d iamino butandiol 2 units. Three diamino alcohol 1 stereotriads were obtaine d by stereoselective addition of alkylmagnesium halides (benzyl, cyclohexyl methyl, and metallyl) to the N-benzyl nitrones derived from beta-amino-alph a-hydroxy aldehydes followed by reduction of the resulting N-benzylhydroxyl amines. Three 1,4-dibenzyl substituted stereoisomers of type 2 with fixed S configuration at C2 and C3 were prepared by sequential and simultaneous am ination in two directions starting from L-threose nitrone and L-tartraldehy de bis-nitrone, respectively. The R,S,S,R isomer obtained by the former rou te was converted into a seven-membered ring cyclic urea (1,3-diazapin-2-one ), i.e., a compound that belongs to a class of nonpeptide HIV-1 protease in hibitors.