Rhodium‐Catalyzed Alkene Difunctionalization with Nitrenes

Abstract

The Rh(II) -catalyzed oxyamination and diamination of alkenes generate 1,2-amino alcohols and 1,2-diamines, respectively, in good to excellent yields and with complete regiocontrol. In the case of diamination, the intramolecular reaction provides an efficient method for the preparation of pyrrolidines, and the intermolecular reaction produces vicinal amines with orthogonal protecting groups. These alkene difunctionalizations proceed by aziridination followed by nucleophilic ring opening induced by an Rh-bound nitrene generated in situ, details of which were uncovered by both experimental and theoretical studies. In particular, DFT calculations show that the nitrogen atom of the putative [Rh]2 =NR metallanitrene intermediate is electrophilic and support an aziridine activation pathway by N⋅⋅⋅N=[Rh]2 bond formation, in addition to the N⋅⋅⋅[Rh]2 =NR coordination mode.

Synthesis of β‐Alkoxy Amines from Alkenes, Sulfonyl Azides, and Alcohols though Copper‐Catalyzed Three‐Component Tandem Reactions via Regioselective Ring‐Opening of Aziridine Intermediates

“…It reported the ring-opening reaction of that aziridine needed harsh reaction conditions. [11,15] Indeed, under the optimized reaction conditions, the target aziridine 11 was isolated in 57% yield, demonstrating aziridine was the real intermediate. Finally, a radical probe experiment was performed by submitting of TEMPO (1.0 equiv) into the optimized reaction conditions (Scheme 7, D).…”

Transition‐Metal‐Catalyzed Three‐Component Difunctionalizations of Alkenes

“…In 2014, the terminal alkenes were also oxyaminated under similar reaction conditions . Mechanistic studies showed that this catalytic cycle involved a key rhodium‐bound nitrene intermediate, which played a dual role by allowing the expected alkene aziridination and then acting as a Lewis acid to activate the aziridine towards the attack of nucleophiles …”

“…[89] Mechanistic studies showedt hat this catalytic cycle involved ak ey rhodium-bound nitrene intermediate, which played ad ual role by allowing the expected alkene aziridinationa nd then acting as aL ewis acid to activate the aziridine towards the attack of nucleophiles. [90] This three-componentd ifunctionalization of alkenes could also be mediated by,f or example, Fe, [91] Ag, [92] Co, [93] Mn, [94] and so on. [95] Various functionalized alkanes were readily synthesized by those methods.…”

Late‐stage Rh(II)‐catalyzed Nitrene Transfer for the Synthesis of Guaianolide Analogs with Enhanced Antiproliferative Activity

“…The inspection of NMR spectroscopic data clearly showed that compound 3 results from the aziridine ring-opening by pivaloic acid released from the iodine (III) oxidant, as previously reported by one of us. [21] The aziridine opening at C- 13 The amination reaction of 11,13-Dihydroachalensolide under these conditions afforded the sole compound 4 with 5 % yield. Analysis of the NMR spectra showed the disappearance of one methine from the substrate and the presence of a quaternary carbon at δ 70.1 assigned to the C-1 position.…”

“…The inspection of NMR spectroscopic data clearly showed that compound 3 results from the aziridine ring-opening by pivaloic acid released from the iodine (III) oxidant, as previously reported by one of us. [21] The aziridine opening at C-13 was proposed based on the appearance of the signals corresponding to the pivaloyloxy group [δ H 1.24 (s, H 3 -3''), δ C 177.4 (C-1''), δ C 39.0 (C-2''), and δ C 27.2 (C-3'')] and the upfield shifts of the CH 2 -13 methylene signals from δ C 36.6, δ H 3.10, and δ H 2.99 for compound 2 to δ C 64.3, δ H 4.53, and δ H 4.39 for compound 3. The pattern of substitution at C-11 was confirmed through the correlation observed in the HMBC spectrum between H 2 -13 and C-12 (δ 172.7) and C-1'' (δ 177.4) (see Figure S11 Supporting Information).…”