David Voigtlaender
4 Papers
David Voigtlaender is an academic researcher. The author has contributed to research in topics: Enantioselective synthesis & Catalysis. The author has an hindex of 1, co-authored 4 publications.
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Papers
Efficient Enantioselective Synthesis of Optically Active Diols by Asymmetric Hydrogenation with Modular Chiral Metal Catalysts
TL;DR: A general, reductive, and highly enantioselective synthesis of aliphatic 1,2-diols has not been reported previously and particular attention was given to nonsymmetric ligands as these were considered more suitable for the enantioface differentiation of the alkyl hydroxy ketones, which are more challenging substrates.
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Efficient Enantioselective Synthesis of Optically Active Diols by Asymmetric Hydrogenation with Modular Chiral Metal Catalysts.
Abstract: The enantioselective hydrogenation of prochiral ketones is one of the most elegant and effective methods for the preparation of optically active secondary alcohols. With regard to the environment, asymmetric hydrogenations represent a highly efficient and atom-economical process. Multiple applications have been developed using chiral ruthenium complexes with atropisomeric ligands for the synthesis of optically active primary and secondary alcohols. The latter are important building blocks for the synthesis of natural products, pharmaceuticals and, agrochemicals. The development of a general and efficient enantioselective route to terminal, vicinal 1,2-diols still presents a great challenge. These compounds are important chiral building blocks for the synthesis of natural products such as macrodiolides, insect pheromones, b-lactone esterase inhibitors, d-lactones, and many other biologically active substances. 5] In the synthesis of the anti-HIV pharmaceutical Tenofovir and related pharmaceuticals the application of enantiomerically pure (R)-propane-1,2-diol is of critical importance. A further application of terminal optically active 1,2-diols is the resolution of atropisomeric compounds. The asymmetric dihydroxylation of terminal alkenes is the most common method for the preparation for this class of compounds. However, small sterically less demanding alkyl derivatives, such as propene, cannot be enantioselectively oxidized to the diol by asymmetric dihydroxylation, nor to the epoxide by asymmetric epoxidation. The difficulty in the highly enantioselective transformation of small alkyl derivatives arises from the similar steric demands of the two groups adjacent to the carbonyl functionality. The result is poor Re and Si face differentiation for the sterically less demanding alkyl derivatives; in contrast, the sterically more demanding aryl ketones can be readily differentiated (Figure 1). The hydrogenation of a-hydroxy ketones is one alternative for the generation of valuable optically active, terminal 1,2-diols. Good progress has been made in the hydrogenation of the sterically demanding a-hydroxy acetophenones using various ruthenium and iridium catalysts. Rhodium and ruthenium complexes were also successfully applied in asymmetric transfer hydrogenations. Further work concentrated on asymmetric enzymatic reductions. A general, reductive, and highly enantioselective synthesis of aliphatic 1,2-diols has not been reported previously. Therefore, we began our examination of the enantioselective synthesis of optically active diols with the application of a new class of modular diphosphane ligands 1. Particular attention was given to nonsymmetric ligands as these were considered more suitable for the enantioface differentiation of the alkyl hydroxy ketones, which are more challenging substrates. Ligands 1 can be prepared simply in two steps on a large scale and are based on a 2,5-disubstituted thiophene core structure, a chiral phospholane unit, 13] and a readily variable diarylphosphino group (Scheme 1).
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