Rhodium‐Catalyzed Regioselective N²‐Alkylation of Benzotriazoles with Diazo Compounds/Enynones via a Nonclassical Pathway

Abstract

A novel rhodium-catalyzed highly selective N -alkylation of benzotriazoles with diazo compounds/enynones is achieved, providing N -alkylated benzotriazoles in good to excellent yields and with excellent N selectivities. Importantly, different to traditional carbene insertion into X-H (X=N, O etc) bonds, DFT calculations disclose that this selective N -alkylation probably proceeds through a formal 1,3- rather than 1,2-H shift to give the final products.

Blue Light‐Promoted N−H Insertion of Carbazoles, Pyrazoles and 1,2,3‐Triazoles into Aryldiazoacetates

“…Previous metal catalyzed strategies have taken advantage of Cu(I) [12] and Pd(II) [13] -based enantioselective protocols for the NÀ H insertion of carbazoles (Scheme 1a), Au(I) catalysis for the simultaneous cycloisomerization of vinyl diazoacetates and formal NÀ H insertions of the corresponding pyrazoles (Scheme 1b); [14] and Rh(II) catalysis for the NÀ H insertion of benzotriazoles, (Scheme 1c). [15] Scheme 1. Previous metal-catalyzed reports of NÀ H insertion protocols of carbazoles, pyrazoles, and benzotriazoles into aryldiazoacetates.…”

Rhodium‐Catalyzed Regioselective N2‐Alkylation of Benzotriazoles with Diazo Compounds/Enynones via a Nonclassical Pathway

“…All the reactions proceeded smoothly to provide the corresponding N 2 -alkylated products (6i-6m)i ng ood yields and > 99:1 N 2 selectivities.T he structure of 6a was confirmed by singlecrystal X-ray diffraction. [10] In order to understand the mechanism of this highly selective N 2 -alkylation DFT calculations were performed. [14] Thepotential energy surface of the overall catalytic cycle and the critical steps are depicted in Figure S1 (Supporting Information) and Figure 2, respectively.A si sw ell-documented in the literature,t he formation of rhodium carbene (IM1)f rom phenyldiazoacetate (2a)a nd dirhodium complexes via an itrogen extrusion step was found to be af acile and rather exergonic process.…”

“…The1 ,5-proton shift then proceeds smoothly to form an enol intermediate. [10,13] Through enol-to-ketone isomerization, finally the N 2 alkylated product is obtained ( Figure S1).…”

“…Thestructures of 3a and 3s were confirmed by single-crystal X-ray diffraction. [10] As enynones are valuable and stable donor-o rd onor/ donor carbene precursors in many useful transformations, [11][12][13] based on the above results we next turned our attention to use them as coupling partners in this selective N 2alkylation. As described by López and Vicente in the pioneer work for zinc-catalyzed X À Hi nsertion reaction, [13a] they reported that the reaction of 1a with enynone 5a provided N 1 -alkylated product 6a' ' as the major isomer and with 1:4 ratio of 6a/6a' ' (N 2 /N 1 )( Scheme 3).…”

Rh2(esp)2‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines

“…The chemistry of α‐diazocarbonyl compounds has attracted much attention from the synthetic organic and medicinal chemistry community, as it offers a wealth of powerful synthetic transformations including those which involve generation of metal carbene species , . One such transformation, allowing for direct functionalization of a carbo‐ or heterocyclic core, is the formal insertion of metal carbenes into the N–H bond of aromatic and aliphatic amines, amides, as well as azaheterocycles , . However, quite a number of chemistries involving α‐diazocarbonyl compounds remain unexplored for some medicinally useful cores, and thus has not been validated for use in drug design.…”