Non-C₂-Symmetric Chiral-at-Ruthenium Catalyst for Highly Efficient Enantioselective Intramolecular C(sp³)–H Amidation

Abstract

A new class of chiral ruthenium catalysts is introduced in which ruthenium is cyclometalated by two 7methyl-1,7-phenanthrolinium heterocycles, resulting in chelating pyridylidene remote N-heterocyclic carbene ligands (rNHCs). The overall chirality results from a stereogenic metal center featuring either a Λ or Δ absolute configuration. This work features the importance of the relative metal-centered stereochemistry. Only the non-C 2 -symmetric chiral-at-ruthenium complexes display unprecedented catalytic activity for the intramolecular C(sp 3 )−H amidation of 1,4,2-dioxazol-5-ones to provide chiral γ-lactams with up to 99:1 er and catalyst loadings down to 0.005 mol % (up to 11 200 TON), while the C 2 -symmetric diastereomer favors an undesired Curtiustype rearrangement. DFT calculations elucidate the origins of the superior C−H amidation reactivity displayed by the non-C 2 -symmetric catalysts compared to related C 2 -symmetric counterparts.

Intramolecular C(sp3)–H Bond Oxygenation by Transition‐Metal Acylnitrenoids

“…Finally, density functional theory (DFT) calculations were performed and provide additional support for the proposed radical mechanism with a 1,5-HAT from a triplet state of the ruthenium intermediate I being the favored pathway (I!II) (see Supporting Information for details on the calculations). [15][16][17] Evidence for the intermediate formation for the iminocarbonate IV, which we were not able to isolate, stems from a reaction shown in Figure 2 d. When we used substrate 1 c, in which the phenyl group is functionalized with a para-methoxy group, we obtained under ruthenium catalysis the carbamate 6 c instead of the cyclic carbonate. This product can be rationalized by a ring opening hydrolysis of the protonated intermediate iminocarbonate IV.…”

Intramolecular C(sp3)–H Bond Oxygenation by Transition‐Metal Acylnitrenoids

“…Finally,density functional theory (DFT) calculations were performed and provide additional support for the proposed radical mechanism with a1 ,5-HATf rom at riplet state of the ruthenium intermediate I being the favored pathway (I!II)( see Supporting Information for details on the calculations). [15][16][17] Evidence for the intermediate formation for the iminocarbonate IV,w hich we were not able to isolate,s tems from areaction shown in Figure 2d.Whenweused substrate 1c,in which the phenyl group is functionalized with a para-methoxy group,weobtained under ruthenium catalysis the carbamate 6c instead of the cyclic carbonate.T his product can be rationalized by ar ing opening hydrolysis of the protonated intermediate iminocarbonate IV. [14] In summary,t he control experiments provide strong support for the proposed radical pathway,w hich can explain the competing C À Oa nd C À N bond formations.…”

“…A trapping experiment of substrate ( E )‐ 1 b with 4‐methoxy‐TEMPO which afforded the TEMPO adduct 5 (11 %) provides a further indication for a radical pathway (Figure 2 c). Finally, density functional theory (DFT) calculations were performed and provide additional support for the proposed radical mechanism with a 1,5‐HAT from a triplet state of the ruthenium intermediate I being the favored pathway ( I → II ) (see Supporting Information for details on the calculations) [15–17] …”

Control of Dynamic sp3-C Stereochemistry

“…On the other hand, the cage adapts its configuration to minimize steric interactions with nearby fixed stereogenic elements and, in so doing, is able to transmit the stereochemical information across its rigid, tricyclic backbone. When interfaced with transition metal complexes, the dynamic cage conveys a stereochemical preference to the chiral-at-metal 41,42 centre. Controllable and adaptable sp -carbon stereochemistry of this kind can be exploited in enantioselective synthesis 7,9,10,28,38,47,48 and chiral functional materials.…”