Solvent-free kinetic resolution of primary amines catalyzed by Candida antarctica lipase B: effect of immobilization and recycling stability

Highly enantioselective (E >200) N-acylation of nine racemic primary amines with isopropyl methoxyacetate in the presence of Candida antarctica lipase B (Novozym 435) has been reported to yield the unreacted (S)-amines (ee ⩾98%) and produced the (R)-amides (ee ⩾95%) at 50% conversion under solvent-free conditions. One of the amines and the acyl donor have been used in an equimolar ratio at room temperature (23 °C). Under the reaction conditions, the reuse stability of Novozym 435 with 1-phenylethylamine (as a model compound) has been shown to be poor while somewhat improved stability has been observed with an in-house prepared sol–gel CAL-B catalyst.

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(R)-N-(1-(4-Fluorophenyl)ethyl)-2-methoxyacetamideC11H14FNO2Ee = 97%[α]D25=+84.7 (c 1, CHCl3)Source of chirality: enzymatic resolution by Candida antarctica lipase BAbsolute configuration: (R)

(R)-N-(1-(4-Chlorophenyl)ethyl)-2-methoxyacetamideC11H14ClNO2Ee = 98%[α]D25=+102 (c 1, CHCl3)Source of chirality: enzymatic resolution by Candida antarctica lipase BAbsolute configuration: (R)

(R)-2-Methoxy-N-(4-phenylbutan-2-yl)acetamideC13H19NO2Ee = 98%[α]D25=+34.1 (c 1, CHCl3)Source of chirality: enzymatic resolution by Candida antarctica lipase BAbsolute configuration: (R)

(R)-2-Methoxy-N-(1,2,3,4-tetrahydronaphthalen-1-yl)acetamideC13H17NO2Ee = 99%[α]D25=+75.7 (c 1, CHCl3)Source of chirality: enzymatic resolution by Candida antarctica lipase BAbsolute configuration: (R)