Copper-catalyzed methylative difunctionalization of alkenes

Abstract

Trifluoromethylative difunctionalization and hydrofunctionalization of unactivated alkenes have been developed into powerful synthetic methodologies. On the other hand, methylative difunctionalization of olefins remains an unexplored research field. We report in this paper the Cu-catalyzed alkoxy methylation, azido methylation of alkenes using dicumyl peroxide (DCP), and di-tert-butyl peroxide (DTBP) as methyl sources. Using functionalized alkenes bearing a tethered nucleophile (alcohol, carboxylic acid, and sulfonamide), methylative cycloetherification, lactonization, and cycloamination processes are subsequently developed for the construction of important heterocycles such as 2,2-disubstituted tetrahydrofurans, tetrahydropyrans, γ-lactones, and pyrrolidines with concurrent generation of a quaternary carbon center. The results of control experiments suggest that the 1,2-alkoxy methylation of alkenes goes through a radical-cation crossover mechanism, whereas the 1,2-azido methylation proceeds via a radical addition and Cu-mediated azide transfer process.

Copper-catalyzed remote C(sp3)–H azidation and oxidative trifluoromethylation of benzohydrazides

“…Methoxylated product was not observed. This result together with the fact that isoindolinone 53–55 was not formed under our conditions are in accord with the Cu-mediated redox azido transfer mechanism 50,51 .…”

“…We focused on the use of stable and readily available TMSN 3 as an azide source and the benzohydrazides 3 41,42 as precursors of amidyl radicals. In line with our working hypothesis and knowing that peroxide is compatible with the Cu-catalyzed carboazidation process 50,51 , the reaction of 3a (R 2 = Me, R = R 1 = H) with TMSN 3 was investigated in the presence of copper salts and peroxides. After systematic screening of the copper sources [CuCl, CuBr, CuI, CuOTf·benzene, Cu(MeCN) 4 PF 6 , Cu(OAc) 2 , Cu(OTf) 2 , CuSO 4 , Cu(acac) 2 , Cu(ClO 4 ) 2 ], the peroxides ( t BuOOH, t BuOO t Bu, cumene hydroperoxide, PhCO 2 O t Bu, MeCO 2 O t Bu), and the solvents ( t BuOH, DCE, 1,4-dioxane, MeCN, CF 3 CH 2 OH), the optimum conditions found consisted of heating a t BuOH solution of 3a ( c 0.05 M) and TMSN 3 (2.0 equiv) at 50 °C in the presence of Cu(MeCN) 4 PF 6 (0.4 equiv) and MeCO 2 O t Bu (2.0 equiv, 50 wt.…”

Intermolecular radical carboamination of alkenes

“…Later, Cu catalyzed three-component radical azidomethylation of aryl alkenes was reported by the Zhu group (Scheme 30). 89 Di-tert-butyl peroxide first gets reduced by Cu(I) via SET to give a tert-butyloxyl radical 133, which undergoes fragmentation to generate a methyl radical 134 that adds to an alkene to give the C-radical 135. Cu(II)-mediated azide transfer provides the desired azidomethylation product 132 along with the starting Cu(I)-complex.…”

Topological magnon nodal lines and absence of magnon spin Nernst effect in layered collinear antiferromagnets

“…Moreover, recent theoretical work has predicted that the DM interaction can induce topological DNL magnons in the 3D collinear antiferromagnet Cu 3 TeO 6 [31]. However, the spin canting induced by the DM interaction was found to be very negligible, hence no evidence of DNL magnons was observed in recent inelastic neutron scattering experiments on Cu 3 TeO 6 [32,33]. Thus, 3D topological DNL magnonic phase has not yet been found in real magnetically ordered materials.…”

“…In addition, the antiferromagnetic material Cu 3 TeO 6 shows very complex structure. For instance, the bulk material has 12 sites in the unit cell and up to ninth nearest-neighbour interactions [32,33], which are very difficult to comprehend analytically. Therefore, we seek for a simpler 3D collinear antiferromagnetic system in which the 3D topological DNL magnonic phase predicted in the collinear antiferromagnet Cu 3 TeO 6 can be clearly manifested.…”