Controlling the Selectivity of C–H Activation in Pyridinium Triazolylidene Iridium Complexes: Mechanistic Details and Influence of Remote Substituents

Abstract

Iridium complexes containing a triazolylidene ligand with an appended methylpyridinium site undergo either aromatic C(sp2)–H bond activation or exocyclic C(sp3)–H bond activation of the N-bound methyl group. The selectivity of these bond activations is controlled by the remote substituent R of the triazolylidene ligand. Iterative computational and synthetic experiments provide evidence for more facile C(sp2)–H bond activation for a variety of remote substituents with R = Me, CH2C6F5, CH2CH2C6H5. For triazolylidene ligands with a benzylic substituent, C(sp2)–H bond activation of this benzylic group is the lowest energy pathway and is competitive with aromatic pyridinium C–H bond activation. The generated cyclometalated species is metastable and undergoes, via an oxidative addition/reductive elimination sequence, a transcyclometalation with exclusive activation of the methyl C–H bond and thus leads to the C(sp3)–H bond activated product. An experimental determination of activation energies as well as isomer ratios of the intermediates validates the computed pathways. The application of a transcyclometalation procedure to activate more challenging C(sp3)–H bonds is unprecedented and constitutes an attractive concept for devising catalytic processes.

Generation of Oxazolidine‐2,4‐diones Bearing Sulfur‐Substituted Quaternary Carbon Atoms by Oxothiolation/Cyclization of Ynamides

“…A chlorine atom in the products can be used to introduce new groups for the synthesis of new bioactive products. For example, upon reaction with sodium azide, 2 a could easily afford the corresponding azido thiooxazolidine‐2,4‐dione 2 aI in 80 % yield . The copper‐catalyzed azide–alkyne cycloaddition reaction of 2 aI with phenylacetylene could produce the triazole derivative 2 aII in 77 % yield (Scheme ) .…”

“…Next, we explored the oxidative cyclization betweenv arious benzenesulfenyl chlorides 5 andy namide 1a ( Table 2, entries [12][13][14][15][16][17][18][19][20][21].N otably,d ifferent positions of the aryl ring did not affect the product yields, and various benzenesulfenyl chlorides with am ethyl group on the ortho, meta,a nd para positions of the aryl ring were converted into the corresponding products in 79-87 %y ields ( Table 2, entries [12][13][14][15]. The reaction was compatible with both the electron-donating (tBu and methoxy) and electron-withdrawing (trifluoromethyl) groups substituted on benzenesulfenyl chlorides 5f-5h (Table2,e ntries 16 and 17), but ab enzenesulfenyl chloride with as trong electron-withdrawingg roup afforded al ower yield ( Table 2, entry 18).…”

“…Meanwhile, the para effect was not obviousf or methyl, bromo, or chloro groups on the para positiono ft he N-aryl ring in the reaction (Table 4, entries [13][14][15]. Ynamides possessing benzyl, 2-naphthyl, and benzo[d][1,3]-dioxol-5-yl groups on theNatomc ould succeed in producing the desired oxazolidine-2,4-diones in 59-72 %y ields (Table 4, entries [16][17][18]. Ynamides with an N-butyl or N-isopropyl group were also good substrates for this reaction andp rovidedt he desired products 3as and 3at in moderate yields (Table 4, entries 19 and 20).…”

“…For example, upon reactionw ith sodium azide, 2a could easily afford the corresponding azido thiooxazolidine-2,4-dione 2aI in 80 %y ield. [16] The copper-catalyzed azide-alkynec ycloaddition reactiono f2aI with phenylacetylene could produce the triazole derivative 2aII in 77 %y ield (Scheme 4). [17] Unsatisfactorily,t he attempted ring-opening reaction of oxazolidine-2,4dione 3aa failed to provide the corresponding thioacrylamide 3aaI and gave 4-methylbenzenethiola nd the a-keto amide.…”

A leap forward in iridium–NHC catalysis: new horizons and mechanistic insights

“…For example, theoretical calculations support the fact that C-H bond activation may take place at room temperature through an Ir(V) intermediate when sufficiently strongly donating carbene ligands are employed. 179 Perhaps more importantly, high electron density at an Ir(III) centre may trigger σ-CAM reactions, where the Ir centre at the transition state formally takes on an oxidation state between III and V, which would be, overall, the equivalent of an oxidative addition followed by reductive elimination.…”