Chemoenzymatic Synthesis of Chiral 1-Benzyl-5-(hydroxymethyl)- 2-piperidone Enabled by Lipase AK-Mediated Desymmetrization of Prochiral 1,3-Diol and Its Diacetate

Abstract

The synthesis of (R)-1-benzyl-5-(hydroxymethyl)-2-piperidone (1) from key synthon monoacetate (R)-3 has been accomplished conveniently in 6 steps with 93 % ee and in 44 % overall yield. The key step involved lipase AK-mediated desymmetrization of diol 4 to produce monoacetate (R)-3 in 93 % ee and 93 % yield. Additionally, lipase AK-mediated desymmetrization of diacetate 5 readily provided access to monoacetate (S)-3 in 93 % ee and 54 % yield