Substrate engineering: Effects of different N-protecting groups in the CAL-B-catalysed asymmetric O-acylation of 1-hydroxymethyl-tetrahydro-β-carbolines

Rita Megyesi, Enikő Forró, Ferenc Fülöp

Index: 10.1016/j.tet.2018.04.012

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Abstract

In the frame of substrate engineering, the steric effect of different N-protecting groups on the enantioselectivity and reaction rate of CAL-B-catalysed (S)-selective O-acylation of N-protected 1-hydroxymethyl-tetrahydro-β-carbolines was investigated. Excellent enantioselectivities (E > 200) were observed when the acylation of N-Boc [(±)-1], N-Cbz [(±)-3], and N-Fmoc-protected [(±)-4] substrates was performed with the use of CAL-B and acetic anhydride in toluene at 60 °C. The resolution of N-acetyl-protected substrate (±)-2 showed excellent E (>200) after 30 min, but as the reaction progressed, E started decreasing after 2 days, because of N→O and O→N acyl migrations. Preparative resolutions of (±)-3 and (±)-4 resulted in unreacted amino alcohols (R)-3 and (R)-4 and esters (S)-7a and (S)-8a with good enantiomeric excesses (≥88%) and high yields (≥44%).