Synthesis of N-alkylated amino acids using fluorous-tagged hydroxylamines

TY - JOUR

T1 - Synthesis of N-alkylated amino acids using fluorous-tagged hydroxylamines

AU - Nielsen, Simon Dalsgaard

AU - Smith, Garrick P

AU - Begtrup, Mikael

AU - Kristensen, Jesper Langgaard

N1 - Keywords: amino acids, petasis reaction, N-O linker, fluorous synthesis

PY - 2011/7/22

Y1 - 2011/7/22

N2 - The development of a new fluorous-tagged ammonia-equivalent for the synthesis of N-alkylated amino acids is described. The required building blocks were readily accessed in high yield and purity using F-SPE purification technique. Coupling of the fluorous-tagged hydroxylamines with a selection of boronic acids and glyoxalic acid gave the desired N-alkylated amino acids. Subsequent removal of the fluorous tag via catalytic hydrogenation was investigated using a number of different catalysts and solvents. A more robust de-tagging procedure involves the transformation of the amino acid to the corresponding methyl ester followed by a Mo(CH3CN) 3(CO)3 mediated N-O bond cleavage.

AB - The development of a new fluorous-tagged ammonia-equivalent for the synthesis of N-alkylated amino acids is described. The required building blocks were readily accessed in high yield and purity using F-SPE purification technique. Coupling of the fluorous-tagged hydroxylamines with a selection of boronic acids and glyoxalic acid gave the desired N-alkylated amino acids. Subsequent removal of the fluorous tag via catalytic hydrogenation was investigated using a number of different catalysts and solvents. A more robust de-tagging procedure involves the transformation of the amino acid to the corresponding methyl ester followed by a Mo(CH3CN) 3(CO)3 mediated N-O bond cleavage.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.tet.2011.05.039

DO - 10.1016/j.tet.2011.05.039

M3 - Journal article

SN - 0040-4020

VL - 67

SP - 5261

EP - 5267

JO - Tetrahedron

JF - Tetrahedron

IS - 29

ER -