Stereoselective Bioreduction of Telluro‐Acetophenones to Optically Active Hydroxy Tellurides

Abstract

Organotellurium compounds exhibit a broad range of useful applications in organic synthesis, materials science and medicinal chemistry fields. Despite their increasing applicability, the synthesis of enantiomerically pure organotellurium compounds remains nowadays scarcely reported in the literature. Herein, the chemical synthesis and biocatalyzed reductions of a set of telluro‐acetophenones using both (R) and (S)‐selective alcohol dehydrogenases (ADHs) is described for the first time, obtaining enantiomerically enriched hydroxy tellurides with excellent selectivities under very mild reaction conditions. On the one hand, enantiopure para‐substituted (S)‐hydroxy tellurides were obtained using the Ras‐ADH (77–95 % conversion) and ADH‐A (52–75 %), the ADH‐A leading to the enantiopure (S)‐hydroxy tellurides substituted at the meta‐position (69–75 %). On the other hand, the evo‐1.1.200 displayed high selectivity towards the preparation of optically alcohols with substitutions at the para‐position of the aromatic ring (60–68 % conversion and 92–97 % ee), while the Lb‐ADH led to the best results when reducing bulky ketones at the meta‐position (79–82% conversion and 88–99 % ee).

Alcohol Dehydrogenases as Catalysts in Organic Synthesis

“…This is also why "chemical" regeneration systems represent a viable alternative to enzymatic counterparts. The preferred stoichiometric electron acceptor is molecular oxygen because of the high thermodynamic driving force of O 2 reduction on the one hand and because of the favorable byproducts (H 2 O or H 2 O 2 , which is generally (Bandeira et al, 2020), [h] RsADH (from Rhodococcus sp.) (Rosen et al, 2006).…”

“…Ketones comprising one large and one small substituent at the carbonyl group are very common substrates for ADH-catalysed reductions. Especially methyl ketones are popular starting materials and a broad range of aliphatic (Sinha and Keinan, 1997), aromatic (Hamada et al, 2001;Stampfer et al, 2002;Hummel et al, 2003;Gonzalez-Martinez et al, 2019;Bandeira et al, 2020), and conjugated ketones (Schubert et al, 2001;Sgalla et al, 2007;Albarrán-Velo et al, 2020;González-Granda et al, 2021) have been reported. Figure 11 shows a representative selection of chiral alcohols obtained from the reduction of methyl ketones.…”