Symmetrical Catalysis and C-H Activation in Unsaturated Amides and Esters of Osmium: Applications in Pharmaceuticals Drug Synthesis

We report the selective activation and transformation of unsaturated amides and esters at multinuclear osmium carbonyl clusters and clarify how these symmetry-enabled, cooperative reactions inform pharmaceutical synthesis. Treatment of the activated triosmium complex Os3(CO)10(NCCH3)2 with N,N-dimethylacrylamide (DMA) or methylacrylate (MA) furnishes eight structurally characterized products spanning Os2, Os3, Os4, Os5, and Os6 nuclearities. Single-crystal X-ray diffraction, IR, NMR, and MS data establish (i) β-C–H activation of the alkene unit to give bridg- ing μ-alkenyl/μ-hydride motifs, (ii) substrate–substrate coupling on the cluster to form a chelated DMA–DMA dimer, and (iii) carbonylation/decarbonylation events that reorganize Os–Os connectivity. The key intermediate HOs3(CO)10(μ-acryloyl) maps a stepwise sequence in which two or more metal centers share bond-making/bond-breaking—an intrinsic “symmetrical catalysis" element arising from the defined Os–Os edges. Solvent governs pathway selection: noncoordinating, higher-boiling media (e.g., heptane) favor direct C–H activation and dimerization, whereas CH2Cl2 enables gentler transformations that preserve cluster integrity and access higher nuclearities. Although the ransformations are stoichiometric, they recapitulate catalytic elementary steps central to late-stage functionalization and feedstock upgrading—concerted C–H cleavage, migratory insertion of CO, and controlled C–C coupling—and thus offer design rules for bimetallic/cluster catalysts targeting drug-like motifs (enamides, dienamides, and 1,4-dicarbonyl frameworks). By linking structure, mechanism, and chemoselectivity across a family of symmetric Os clusters, this work provides a mechanistic platform for translating cooperative multimetal activation into future catalytic processes relevant to API synthesis and process intensification.