Unveiling Latent α‐Iminocarbene Reactivity for Intermolecular Cascade Reactions through Alkyne Oxidative Amination

Abstract

The chemistry of reactive (electrophilic) metallocarbenes, primarily obtained by metal-catalyzed decomposition of adiazocarbonyl compounds, has been extensively developed and offers significant opportunity for strategic CÀC, CÀO, and CÀN bond formation through a variety of well-defined reaction mechanisms. [1] Given the prevalence of nitrogen atoms in biologically and pharmaceutically relevant molecules and the intrinsic electronic similarities between carbonyl and imine functional groups, the development of analogous metallocarbene chemistry with an a imine providing the necessary electrophilic activation represents both an obvious and synthetically important extension of this chemistry. However, the requisite a-diazoimine precursors readily isomerize to 1,2,3-triazoles, and these heterocycles were long believed to represent a thermodynamic sink, thus significantly delaying the development of metallocarbene chemistry associated with such systems. [2] Nonetheless, the perception that reliable methods to access a-iminocarbene chemistry would offer the potential to build structurally complex nitrogen-containing molecules in a remarkably efficient manner has recently resulted in the development of several complementary solutions to the a-diazoimine isomerization problem (Scheme 1).Specifically, Park and co-workers showed that b oximinoesters can be diazotized with minimal rearrangement to the isomeric triazoles, thus providing an entry into a-oximino acceptor-acceptor carbenoid chemistry. [3] More generally, Fokin and co-workers demonstrated that 1,2,3-triazoles can themselves act as precursors to a-iminometallocarbene intermediates, participating predictably in a range of traditional metallocarbene reactions to generate a-functionalized imine products. [4] Implicit in this strategy is the recognition that alkynes can serve as precursors to both a-oxy-and aiminocarbenes and that oxidation of an alkyne under appropriate reaction conditions could serve to reveal the desired reactive intermediate. [5] The approach of Raushel and Fokin separates the alkyne oxidation, which is achieved through copper-catalyzed azide-alkyne cycloaddition, [6] from the rhodium-catalyzed metallocarbene generation.Studies in our laboratory have focused on the direct unveiling of an intermediate with an a-iminometallocarbene reactivity profile by a metallonitrene-initiated oxidative cascade process. In intramolecular settings we have demonstrated the feasibility of this direct approach, terminating the cascade in an array of predictable carbene reactions (oxygenylide formation/[2,3] Wittig rearrangement, [7] electrophilic aromatic substitution, and cyclopropanation). [8] Despite the inherent attractiveness of this single-step approach, reaction conditions that facilitate efficient intermolecular cascade termination are required for broad applicability and synthetic utility. Herein we describe the development of a metallonitrene-initiated alkyne oxidation cascade with intermolecular trapping of the reactive intermediate by a variety of allyl ...

Chemoselective Amination of Propargylic C(sp3)H Bonds by Cobalt(II)‐Based Metalloradical Catalysis

“…While metal-catalyzed amination has been successfully demonstrated with several different types of C–H substrates, [7] few catalytic systems are known for chemoselective amination of propargylic C(sp 3 )–H bonds. [8a,9] Due to the electrophilic nature of the key metallonitrene intermediates, its addition to more electron-rich C≡C π bonds would be typically preferred over amination of the propargylic C–H σ bonds for propargylic C–H substrates. [8] Through decreasing the electrophilicity of the corresponding Rh 2 -nitrene intermediates by replacing sulfamates with carbamates, Schomaker and coworkers reported recently that intramolecular propargylic C–H amination of homopropargylic carbamates could be successfully catalyzed by Rh 2 (esp) 2 in combination with PhI(OAc) 2 and MgO, generating 5-membered propargylamine derivatives in good yields.…”

“…[8a,9] Due to the electrophilic nature of the key metallonitrene intermediates, its addition to more electron-rich C≡C π bonds would be typically preferred over amination of the propargylic C–H σ bonds for propargylic C–H substrates. [8] Through decreasing the electrophilicity of the corresponding Rh 2 -nitrene intermediates by replacing sulfamates with carbamates, Schomaker and coworkers reported recently that intramolecular propargylic C–H amination of homopropargylic carbamates could be successfully catalyzed by Rh 2 (esp) 2 in combination with PhI(OAc) 2 and MgO, generating 5-membered propargylamine derivatives in good yields. [9a] However, due to the competitive electrophilic addition of Rh 2 -nitrene intermediate to the electron-rich C≡C π bonds under these catalytic conditions, [8a] the intramolecular propargylic C–H amination of sulfamates gave the corresponding 6-membered propargylamines in only moderate yields.…”

“…[8] Through decreasing the electrophilicity of the corresponding Rh 2 -nitrene intermediates by replacing sulfamates with carbamates, Schomaker and coworkers reported recently that intramolecular propargylic C–H amination of homopropargylic carbamates could be successfully catalyzed by Rh 2 (esp) 2 in combination with PhI(OAc) 2 and MgO, generating 5-membered propargylamine derivatives in good yields. [9a] However, due to the competitive electrophilic addition of Rh 2 -nitrene intermediate to the electron-rich C≡C π bonds under these catalytic conditions, [8a] the intramolecular propargylic C–H amination of sulfamates gave the corresponding 6-membered propargylamines in only moderate yields. [8a,9a] It should be noted that the ring size of the resulting heterocycles from intramolecular C–H amination is typically governed by the substrate geometry and tether length of the substrates.…”

“…[9a] However, due to the competitive electrophilic addition of Rh 2 -nitrene intermediate to the electron-rich C≡C π bonds under these catalytic conditions, [8a] the intramolecular propargylic C–H amination of sulfamates gave the corresponding 6-membered propargylamines in only moderate yields. [8a,9a] It should be noted that the ring size of the resulting heterocycles from intramolecular C–H amination is typically governed by the substrate geometry and tether length of the substrates. [7a] …”

Metal‐Free Ring‐Expansion Reaction of Six‐membered Sulfonylimines with Diazomethanes: An Approach toward Seven‐Membered Enesulfonamides

“…[1c,2-5] Despite being appealing structural motifs,only few metal-catalyzed methods for the synthesis of these compounds have been reported. [1f, 2-5] Major synthetic methods consist of:1 )Rhodium-or iron-catalyzed intramolecular allylic CÀHamination; [2] 2) Rhodium-catalyzed intramolecular alkyne or allene amination; [3,4] 3) Copper-catalyzed intramolecular nucleophilic ring-opening of sulfamate-derived aziridines; [5] 4) Scandium-or lutetium-catalyzed haloaminocyclization of primary sulfamate ester derivatives. [1f] Despite great achievements in metal-catalyzed reactions,t he discovery of efficient metal-free reactions will also be of great importance because of the reduced toxicity and elimination of the cost of the metal.…”