Two breeds of cat: A palladium‐catalyzed Suzuki cross‐coupling and an enzymatic reduction with an alcohol dehydrogenase from Rhodococcus sp. together enable the efficient and highly enantioselective synthesis of chiral biaryl alcohols in a one‐pot process (see scheme).

Chiral 1,3-diols with two stereogenic centers are widely used as building blocks in the synthesis of pharmaceutically active compounds.[1] In addition, numerous natural products possess a chiral 1,3-diol subunit.[2] A further interesting application of chiral 1,3-diols is their transformation into chiral 1,3-bisphosphanes, which are often used very successfully as enantiomerically pure ligands in asymmetric catalysis.[3] Accordingly, there is a high demand for stereoselective synthetic processes to generate chiral 1,3-diols with two stereogenic centers (e.g., of the type 4; Scheme 1), which ideally should allow the synthesis of all stereoisomers in a diastereo-and enantiomerically pure form.[4] To date, efficient synthetic routes [2] are based, in particular, on the enantio-and diastereoselective reduction of 1,3-diketones by hydrogenation with metal catalysts [4a] and enzymes [4b] or chemoenzymatic processes by dynamic kinetic resolution.[4c] A limitation of these methods is often their applicability for only one or two of the four maximum possible stereoisomers. In contrast, methods which offer an approach to all four stereosiomers in an efficient and convenient way are rarely known. [2] In the following we report a modular chemoenzymatic process for the selective synthesis of all four stereoisomers of 1,3-diols 4 through a combination of asymmetric organocatalysis and biocatalysis. A key feature of this synthetic strategy is the sequential construction of the stereogenic centers. Thus, each stereogenic center can be constructed selectively by means of a catalyst which is specifically suitable for this purpose (Scheme 1). This modular synthetic strategy additionally offers the possibility for a two-step one-pot synthesis.Since organocatalytic syntheses [5,6] are already known for the initial aldol reaction, we first focused on the subsequent diastereoselective enzymatic reduction of b-hydroxy ketones 3 bearing one stereogenic center. Such a study is interesting both from the synthetic perspective of the target molecules 4 and the perspective of the reaction mechanism since chiral ketones are used as substrates. Thus, the effect of the internal stereogenic center of the substrate and the influence of the chiral catalyst (enzyme) on the formation of the second stereogenic center can be compared. Such studies based on the use of redox enzymes are rare, [7] in contrast to the numerous examples of enantioselective reductions of prochiral ketones.[8] A stereoselective reaction course is typically expected when chiral (for example, racemic) substrates are used in an enzymatic reaction, with preferential transformation of only one of the two enantiomers. With respect to a stereoselective construction of all stereoisomers of type 4, however, we were interested in a diastereoselective reaction course which can be directed exclusively (externally) by the enzyme catalyst. In addition to a highly selective formation of the second stereogenic center-depending only on the biocatalyst-both enantiomeric forms of the aldol pro...

No abstract

It doesn′t take much to oxidize cycloalkanes directly to the corresponding cyclic ketones: molecular oxygen as the oxidant, water as the solvent, the cofactor NADP+ (and a little 2‐propanol to reduce it), as well as two catalytic enzymes—a hydroxylating P450 monooxygenase and an alcohol dehydrogenase (see scheme).

No abstract