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 ...

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 ...

Unveiling Latent α-Iminocarbene Reactivity for Intermolecular Cascade Reactions Through Alkyne Oxidative Amination. -The present protocol provides a metallonitrene/alkyne cascade which is terminated by ylide formation and [2,3] Wittig rearrangement. Efficient transfer of stereochemical information is observed when using enantio-enriched allyl ethers. The synthetic value of this method is demonstrated by preparation of compound (XIV), which constitutes the AB ring core of the segurinega alkaloid viroallosecurinine. -(MACE, N.; THORNTON, A. R.; BLAKEY*, S. B.; Angew. Chem., Int. Ed. 52 (2013) 22, 5836-5839, http://dx.