Modern dehydrogenative amination reactions

Nitrogen element is preponderant in Nature. Found in its simplest form as diatomic gas in the air, as well as in elaborated molecules such as the double helix of DNA, this element is indisputably essential for life. Indeed, nitrogen is omnipresent in all metabolic pathways. With the advent of green chemistry, researchers attempt to functionalize arenes without pre-functionalization of the later for the establishment of C-C bond formation. Why not C-N bond formation? We investigated new oxidative amination reactions by cross-dehydrogenative-coupling. Concerned by atom economy and green processes, our objectives were: 1) to obviate pre-activation or pre-oxidation of both C-H coupling partner and N-aminating agent. 2) to avoid the use of chelating directing group. We achieved C-N bond formation for some classes of amines. Thus, we will describe the reactivity of cyclic secondary amines: carbazole, in presence of catalytic amount of ruthenium (II) and copper (II) to build the challenging C-N bond between two carbazoles. The initial mechanistic experiments will be present and discuss. Then, we will describe more challenging hetero-coupling formation between diarylamines and carbazoles. The new ruthenium (II)/ copper (II) catalytic system allowed forming the ortho-N-carbazolation of diarylamines. This reaction performed under mild conditions (O2 as terminal oxidant) displays an unusual intramolecular N-H••N interaction in the novel class of compounds. Finally, we will present a surprising metal free C-N bond formation between the ubiquitous phenols and the phenothiazines. Initially conducted in the presence of transition metals (RuII/CuII), this reaction proved to be efficient with the only effect of cumene and O2. Those components suggest a mechanism initiated by a Hock process. An initial infra-red analysis might point out a strong intramolecular O-H••N interaction in the resulting products. These first elements of reactivity, developed within the laboratory for “modern dehydrogenative amination reactions”, will be presented and discussed

para-Selective C-H amidation of simple arenes with nitriles

A para-selective C-H amidation of simple arenes with nitriles has been developed. By increasing the amount of arenes, a further meta-selective C-H arylation of the produced amides occurred. Both steric and electronic effects are utilized to control the selectivity, resulting in only para-selective amidation products. The readily available nitriles as amidation reagents instead of amides makes the synthesis of N-arylamides more accessible

Catalytic Nitrene Transfer To Alkynes: A Novel and Versatile Route for the Synthesis of Sulfinamides and Isothiazoles

A novel transformation is reported for the reaction of terminal or internal alkynes with the nitrene precursor PhI=NTs (Ts=p-toluenesulfonyl) in the presence of catalytic amounts of Tp(Br3)Cu(NCMe) (Tp(Br3)=hydrotris(3,4,5-tribromo-pyrazolylborate). Two products containing an imine functionality have been isolated from the reaction mixtures, identified as sulfinamides and isothiazoles. The former correspond to the formal reduction of the sulfone group into sulfoxide, whereas the latter involves the insertion of an alkyne carbon atom into the aromatic ring of the N-tosyl moiety.Support for this work was provided by the MINECO (CTQ2014-52769-C3-R-1, CTQ2014-57761-R, Severo Ochoa Excellence Accreditation 2014-2018 SEV-2013-0319, Red Intecat CTQ2014-52974-REDC) and by a FPU fellowship (M.R.R.). We thank Prof. Antonio Echavarren for helpful comments and discussions

Modern dehydrogenative amination reactions

Nitrogen element is preponderant in Nature. Found in its simplest form as diatomic gas in the air, as well as in elaborated molecules such as the double helix of DNA, this element is indisputably essential for life. Indeed, nitrogen is omnipresent in all metabolic pathways. With the advent of green chemistry, researchers attempt to functionalize arenes without pre-functionalization of the later for the establishment of C-C bond formation. Why not C-N bond formation? We investigated new oxidative amination reactions by cross-dehydrogenative-coupling. Concerned by atom economy and green processes, our objectives were: 1) to obviate pre-activation or pre-oxidation of both C-H coupling partner and N-aminating agent. 2) to avoid the use of chelating directing group. We achieved C-N bond formation for some classes of amines. Thus, we will describe the reactivity of cyclic secondary amines: carbazole, in presence of catalytic amount of ruthenium (II) and copper (II) to build the challenging C-N bond between two carbazoles. The initial mechanistic experiments will be present and discuss. Then, we will describe more challenging hetero-coupling formation between diarylamines and carbazoles. The new ruthenium (II)/ copper (II) catalytic system allowed forming the ortho-N-carbazolation of diarylamines. This reaction performed under mild conditions (O2 as terminal oxidant) displays an unusual intramolecular N-H••N interaction in the novel class of compounds. Finally, we will present a surprising metal free C-N bond formation between the ubiquitous phenols and the phenothiazines. Initially conducted in the presence of transition metals (RuII/CuII), this reaction proved to be efficient with the only effect of cumene and O2. Those components suggest a mechanism initiated by a Hock process. An initial infra-red analysis might point out a strong intramolecular O-H••N interaction in the resulting products. These first elements of reactivity, developed within the laboratory for “modern dehydrogenative amination reactions”, will be presented and discussed

Toward Polynuclear Ru–Cu Catalytic Dehydrogenative C–N Bond Formation, on the Reactivity of Carbazoles

The cooperative action of Ru and Cu catalysts enables direct polynuclear C–H and N–H activation for the dehydrogenative N-carbazolation of carbazoles, selectively at the C1 position. Initial mechanistic experiments are presented and discussed