초록
<P><B>Abstract</B></P><P>The biocatalytic asymmetric disproportionation of aldehydes catalyzed by horse liver alcohol dehydrogenase (HLADH) was assessed in detail on a series of racemic 2‐arylpropanals. Statistical optimization by means of design of experiments (DoE) allowed the identification of critical interdependencies between several reaction parameters and revealed a specific experimental window for reaching an ′optimal compromise′ in the reaction outcome. The biocatalytic system could be applied to a variety of 2‐arylpropanals and granted access in a redox‐neutral manner to enantioenriched (<I>S</I>)‐profens and profenols following a parallel interconnected dynamic asymmetric transformation (PIDAT). The reaction can be performed in aqueous buffer at ambient conditions, does not rely on a sacrificial co‐substrate, and requires only catalytic amounts of cofactor and a single enzyme. The high atom‐efficiency was exemplified by the conversion of 75 mM of <I>rac</I>‐2‐phenylpropanal with 0.03 mol% of HLADH in the presence of ∼0.013 eq. of oxidized nicotinamide adenine dinucleotide (NAD<SUP>+</SUP>), yielding 28.1 mM of (<I>S</I>)‐2‐phenylpropanol in 96% <I>ee</I> and 26.5 mM of (<I>S</I>)‐2‐phenylpropionic acid in 89% <I>ee</I>, in 73% overall conversion. Isolated yield of 62% was obtained on 100 mg‐scale, with intact enantiopurities.</P><P/>