anti-Carbopalladations of C-C Triple Bonds: Mechanistic Investigations and Starting Point for Novel Domino Reactions

• Applicant: Professor Dr. Daniel B. Werz
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2014 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 264267138

This project aims to continue the studies regarding the Pd-catalyzedanti-functionalisation of C-C triple bonds. Previous investigations ledto a fast and efficient access to tetrasubstituted alkenes starting frominternal alkynes. Mechanistic investigations (by experimental andcomputational means) of the unusual anti-carbopalladation being thekey of the investigated domino processes revealed that the initialassumption of a Pd-allene complex as crucial intermediate is notvalid. DFT studies and respective experiments demonstrated thatafter the common syn-carbopalladation of the C-C triple bond anisomerization in the coordination sphere of the metal takes place.Prerequisite is the occurrence of a 14-valence electron complex beingfavored by monodentate and bulky phosphine ligands. With thismechanistic knowledge in hand several domino processes based onanti-carbopalladations have successfully been performed. Cascadesbeing terminated via Heck and Stille reactions, C-H activations or thenucleophilic attack of hydroxyl groups have been designed andrealized. The relevance of these reactions (also for natural productchemistry) was demonstrated by a formal total synthesis of Lysergol.These investigations based on anti-carbopalladation as key step ofcomplex cascades should be continued within the next funding period.Three work packages will be in the focus: (i) termination of thesequence by sp3-hybrized carbon entities, (ii) termination by oxygen,nitrogen and sulfur moieties and (iii) conduction of successfulsequences under an atmosphere of carbon monoxide. The first workpackage aims at the termination with aliphatic boronic acid esters. Inaddition, the work on terminating C-H activation will be extended fromaryl to cyclopropyl residues. The second work package will evaluatewhether also ketones in their enol form and carboxylates mightterminate the cascade. An attack of amines or amides to the key anticarbopalladationintermediate should pave the way to nitrogencontainingheterocycles with embedded enamine unit while sulfinatesshould lead to double bonds substituted with sulfone units. The thirdwork package focuses on the question whether the presence ofcarbon monoxide allows adding carbonylation steps to the cascade.The envisioned investigations will also comprise mechanisticexperiments such as crystallization and trapping of respectiveintermediates.

• DFG Programme: Research Grants