Amidins and Imidates as Transient Directing Groups in C-H-activating Reactions

• Applicant: Professor Dr. Boris J. Nachtsheim
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 406058799

In this research project we want to develop a direct ortho-alkynylation of phenols and anilins under C-H-activating conditions. For this purpose, we want to establish amidines and imidates as novel transient directing groups (tdGs) for alkynylation reactions. By definition, tdGs are installed during the C-H-activating transformation for a better guidance of the transition metal to the desired C-H-bond and finally they are cleaved after a successful functionalization. To guarantee the reversibility of the tdG formation in this specific case, we want to introduce ortho-X-H-acidic aromatic nitriles as their precursors. In a first goal we want to synthesize a variety of such electron poor ortho-X-H-acidic nitriles und transform them into amidines and imidates by direct reaction with well-chosen anilines and phenols. We want to study this important reaction mechanistically, in particular its reversibility. Since amidines as well as imidates have not been described so far in C-H-activating alkynylations, a directed alkynylation under their guidance as “classical” directing group should be established. As electrophilic alkyne source alkynyl(aryl)benziodoxolones will be used. These reagents have been used in a variety of guided C-H-activating reactions since they show a remarkable high reactivity and at the same time they are bench stable and easy to handle. Besides the direct ortho-alkynylation, we want to develop domino-type processes to get an efficient access to a variety of highly substituted heterocycles. From the information that we gained from the initial mechanistic studies regarding the reversibility of the amidine and imidate formation and from the alkynylation reactions, we finally should be able to develop a process that only uses catalytic amounts of the ortho-C-H-acidic nitrile. Here the amidines and imidates are generated in situ as tdGs. In addition, we want to study the regio- and chemoselectivity of this transformation and we want to be able to rationally steer this selectivity.

• DFG Programme: Research Grants
• Major Instrumentation: In-situ FTIR-Spektrometer
• Instrumentation Group: 1830 Fourier-Transform-IR-Spektrometer