Chiral oxime ethers in asymmetric synthesis. O-(1-Phenylbutyl)benzyloxyacetaldoxime, a versatile reagent for the asymmetric synthesis of protected 1,2-aminoalcohols, alpha-amino acid derivatives, and 2-hydroxymethyl nitrogen heterocycles including iminosugars.
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.
Cooper
Tracey S
TS
Department of Chemistry, University of Exeter, Stocker Road, Exeter, UK EX4 4QD.
Larigo
Alexander S
AS
Laurent
Pierre
P
Moody
Christopher J
CJ
Takle
Andrew K
AK
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D050111:Imino Sugars / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry*
D000596:Amino Acids; D000605:Amino Alcohols; D004987:Ethers; D006573:Heterocyclic Compounds, 1-Ring; D050111:Imino Sugars; D010091:Oximes