Addition of a range of organolithium and Grignard reagents to (E)-O-(1-phenylbutyl)benzyloxyacetaldoxime 1 in the presence of boron trifluoride diethyl etherate is highly diastereoselective. The resulting hydroxylamines undergo N-O bond cleavage upon treatment with zinc-acetic acid or molybdenum hexacarbonyl to give, after N-protection, protected 1,2-aminoalcohols 3 in high enantiomeric purity. Debenzylation of 3a and 3d gave N-Boc (R)-alaninol and (S)-phenylalaninol respectively. The hydroxylamines 2 also serve as alpha-amino acid precursors, 2i being converted into N-formyl-(R)-alaninyl-(S)-(4-bromo)phenylalanine ester 7, the N-terminal dipeptide of a natural depsipeptide. The versatility of the 1,2-aminoalcohol derivatives was further illustrated by their conversion into 5-, 6- and 7-membered 2-hydroxymethyl nitrogen heterocycles 15-19 in high enantiomeric excess by a ring-closing metathesis reaction. Further reaction of the dihydropyrrole 15 gave the iminosugar 1,4-dideoxy-1,4-imino-D-ribitol.

Addition of organometallic reagents to O-(1-phenylbutyl)benzyloxyacetaldoxime in the presence of boron trifluoride diethyl etherate is highly diastereoselective; the resulting hydroxylamines are readily converted into protected 1,2-aminoalcohols and 2-hydroxymethyl nitrogen heterocycles, including the iminosugar 1,4-dideoxy-1,4-imino-D-ribitol, in high enantiomeric excess.

Amino alcoholsAmino alcohols P 0130 O-(1-Phenylbutyl)benzyloxyacetaldoxime, a Versatile Reagent for the Asymmetric Synthesis of Protected 1,2-Amino Alcohols and 2-Hydroxymethyl Nitrogen Heterocycles. -The addition reaction of organolithiums or Grignard compounds to the chiral aldoximes (I) proceeds with good diastereoselectivity. The resulting products (III) and (VII) can be readily converted to protected 1,2-amino alcohols and 2-oxymethyl nitrogen heterocycles such as (XII). -(COOPER, T. S.; LARIGO, A. S.; LAURENT, P.; MOODY*, C. J.; TAKLE, A. K.; Synlett 2002, 10, 1730-1732; Sch. Chem., Univ. Exeter, Exeter, Devon EX4 4QD, UK; Eng.) -Mais 05-069

Hydroxylamine derivatives P 0050 Chiral Oxime Ethers in Asymmetric Synthesis. Part 7. O-(1-Phenylbutyl)benzyloxyacetaldoxime, a Versatile Reagent for the Asymmetric Synthesis of Protected 1,2-Aminoalcohols, α-Amino Acid Derivatives, and 2-Hydroxymethyl Nitrogen Heterocycles Including Iminosugars. -The addition of a range of organolithium and Grignard reagents to chiral oxime ethers (I) affords the corresponding hydroxylamines (III) in high diastereomeric excess. The only exception is the addition of allylmagnesium bromide (42% d.e.). Compounds (III) are used as intermediates for the synthesis of a wide range of chiral nitrogen-containing compounds like protected 1,2-amino alcohols, α-amino acid derivatives and 2-hydroxymethyl nitrogen heterocycles including iminosugars. -(COOPER, T. S.; LARIGO, A. S.; LAURENT, P.; MOODY*, C. J.; TAKLE, A. K.; Org. Biomol. Chem. 3 (2005) 7, 1252-1262; Dep. Chem., Univ. Exeter, Exeter, Devon EX4 4QD, UK; Eng.) -Bartels 35-063