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Biocatalytic Parallel Interconnected Dynamic Asymmetric Disproportionation of α‐Substituted Aldehydes: Atom‐Efficient Access to Enantiopure ( S )‐Profens and Profenols
Author(s) -
Tassano Erika,
Faber Kurt,
Hall Mélanie
Publication year - 2018
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201800541
Subject(s) - chemistry , enantiopure drug , disproportionation , catalysis , biocatalysis , yield (engineering) , combinatorial chemistry , substrate (aquarium) , cofactor , alcohol dehydrogenase , alcohol , enantioselective synthesis , organic chemistry , reaction mechanism , enzyme , oceanography , geology , materials science , metallurgy
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 ( S )‐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 rac ‐2‐phenylpropanal with 0.03 mol% of HLADH in the presence of ∼0.013 eq. of oxidized nicotinamide adenine dinucleotide (NAD + ), yielding 28.1 mM of ( S )‐2‐phenylpropanol in 96% ee and 26.5 mM of ( S )‐2‐phenylpropionic acid in 89% ee , in 73% overall conversion. Isolated yield of 62% was obtained on 100 mg‐scale, with intact enantiopurities.