Previously unknown ring closing metathesis reactions of diynes are described which open an efficient and stereoselective entry into macrocyclic (Z)-alkenes if the resulting cycloalkyne products are subjected to Lindlar reduction. This new two-step strategy offers significant advantages in stereochemical terms over conventional RCM of dienes which usually leads to (E,Z)-mixtures when applied to the formation of large rings. The tungsten alkylidyne complex (tBuO)₃W⋮CCMe₃(1a) and analogues thereof as well as a structurally unknown species formed in situ from Mo(CO)₆ and p-chlorophenol effect the crucial alkyne metathesis reactions in a highly efficient manner, with the former catalyst being more tolerant toward structural variations of the substrates and polar functional groups. Applications to the stereoselective synthesis of the olfactory compounds ambrettolide 23 and yuzu lactone 24, the insect repellent azamacrolides epilachnene 31 and homoepilachnene 33, as well as to the fully functional building block 64 required for a total synthesis of the cytotoxic alkaloid nakadomarin A 51 highlight the relevance of this new concept for natural product chemistry. In the latter case, the diyne substrate 62 necessary for ring closing alkyne metathesis was obtained via a novel furan synthesis relying on a palladium-catalyzed opening of a vinyl epoxide followed by an oxidative cyclization of the heterocyclic ring

An optimized and large scale adaptable synthesis of the ruthenium phenylindenylidene complex 3 is described which employs commercially available diphenyl propargyl alcohol 5 as a stable and convenient carbene source. Previous ambiguities as to the actual structure of the complex have been ruled out by a full analysis of its NMR spectra. A series of applications to ring closing metathesis (RCM) reactions shows that complex 3 is as good as or even superior to the classical Grubbs carbene 1 in terms of yield, reaction rate, and tolerance towards polar functional groups. Complex 3 turns out to be the catalyst of choice for the synthesis of the enantiopure core segment 77 of the marine alkaloid nakadomarin A 60 comprising the ADE rings of this target. Together with a series of other examples, this particular application illustrates that catalyst 3 is particularly well suited for the cyclization of medium-sized rings by RCM. Other key steps en route to nakadomarin A are a highly selective intramolecular Michael addition setting the quaternary center at the juncture of the A and D rings and a Takai-Nozaki olefination of aldehyde 73 with CH2I2, Ti(OiPr)4 and activated zinc dust.

Automated parallel synthesis as tool to increase productivity in chemical synthesis is well-established. However, even more time-consuming than the synthesis process is the following purification of the resulting crude products. To enhance efficiency of the lead optimization process at Bayer CropScience, a high-throughput HPLC/MS-laboratory for the purification of up to 48 crude products per day in the range of 200-400 mg each in one injection per sample has been set up. The use of Covaris technology for HPLC sample preparation, automated aliquotation during fractionation, and a novel evaporation process by combination with freeze-drying are new key technologies applied successfully for the first time in this purification unit facilitating to achieve the targeted efficiency. The whole process is supported by a specially designed IT-landscape covering each step of the workflow. Both the technical instruments used within the laboratory and the workflow and IT platform are described in this article.

Jungchemiker der Regionalgruppe Mülheim/Ruhr besuchten Chemie‐Leistungskurse benachbarter Gymnasien — hoffentlich der Beginn eines intensiveren Kontakts zwischen interessierten Schülern und jungen Chemikern.