One‐Pot Selective Syntheses of 5‐Azaindoles through Zirconocene‐Mediated Multicomponent Reactions with Three Different Nitrile Components and One Alkyne Component

Abstract

5-Azaindoles either with three different substituents at their 2-, 4-, and 6-positions or with two identical substituents at their 2- and 6-positions and a different one at the 4-position, were obtained in good to excellent isolated yields by a zirconocene-mediated multicomponent process. Each reaction involved four organic partners, comprising a Si-tethered diyne, one tBuCN component, and two (either different or identical) nitriles. All these four components were combined through the action of a Cp(2)Zr(II) species into a three-ring fused Zr/Si-containing organometallic complex in a perfectly chemo- and regioselective manner. This multicomponent reaction process consisted of three reaction steps, all of which were made clear through the isolation and characterization of their corresponding organometallic intermediates: the zirconacyclopropene-azasilacyclopentadienes 2, the allenyl-aza-zirconacycles 3, and the three-ring fused complexes 6. X-ray single-crystal structural analyses of two three-ring fused Zr/Si-containing intermediates and two 5-azaindoles unambiguously showed the positions of the different substituents and the regioselectivity. Iminopyrrole derivatives could be also highly selectively prepared from a Si-tethered diyne and two different nitriles.

Insertion of Nitriles into Zirconocene 1‐aza‐1,3‐diene Complexes: Chemoselective Synthesis of N–H and N‐Substituted Pyrroles

“…The Zr1–N2 distance of 2.199(2) Å is in the range of a single bond, and the N2 atom is only slightly pyramidalized (summation of bonding angles at N2 356.35°). The N1–C6 distance (1.251(3) Å) corresponds to an imine moiety 8h. The large distances of Zr1–C9 and Zr1–C8 (exceeds 3.0 Å) do not indicate a π interaction between Zr and the CC bond.…”

“…The results indicated that pyrroles were formed after hydrolysis of the zirconacycles. The Zr1–N1 distance of 2.024(2) Å indicates a σ bond between Zr and the sp 2 ‐hybridized imino N atom 8h. The Zr1–N2 distance of 2.199(2) Å is in the range of a single bond, and the N2 atom is only slightly pyramidalized (summation of bonding angles at N2 356.35°).…”

Efficient synthesis of aminomethylated azaindoles and corresponding pyrrole-fused derivatives by copper-catalyzed domino multicomponent coupling and cyclization

“…[8][9][10][11][12][13] However, few methods have been reported for azaindole synthesis based on multiple component reactions, which provide a divergent approach to functionalized azaindoles in a single step. [14][15][16][17] We recently reported the direct synthesis of 2-(aminomethyl)indoles 3 via copper-catalyzed domino threecomponent coupling and cyclization reactions of ethynylaniline 1 (Scheme 1). [18][19][20] The mechanism of this reaction involves the formation of the propargylamine intermediate 2 by Mannich-type three-component coupling of 1 with paraformaldehyde and a secondary amine, and subsequent copper-catalyzed intramolecular cyclization.…”

The Synthesis of Stable, Complex Organocesium Tetramic Acids through the Ugi Reaction and Cesium‐Carbonate‐Promoted Cascades

“…[10] Surprisingly,M CRs in general have been rarely used to synthesize libraries of organometallics, [11][12][13] and to the best of our knowledge there are no reported examples of MCRs affording cesium-based organometallics.W ith an on-going interest in MCRs and molecular diversity generation, [14][15][16] our original intent was to use the Dieckmann condensation [17] on an Ugi adduct to access tetramic acids (pyrrolidine-2,4-diones;S cheme 1). [10] Surprisingly,M CRs in general have been rarely used to synthesize libraries of organometallics, [11][12][13] and to the best of our knowledge there are no reported examples of MCRs affording cesium-based organometallics.W ith an on-going interest in MCRs and molecular diversity generation, [14][15][16] our original intent was to use the Dieckmann condensation [17] on an Ugi adduct to access tetramic acids (pyrrolidine-2,4-diones;S cheme 1).…”

“…Post-condensation strategies to manipulate IMCRs for molecular diversity generation are highly productive for the construction of avariety of heterocyclic scaffolds,particularly in al ibrary compatible manner. [10] Surprisingly,M CRs in general have been rarely used to synthesize libraries of organometallics, [11][12][13] and to the best of our knowledge there are no reported examples of MCRs affording cesium-based organometallics.W ith an on-going interest in MCRs and molecular diversity generation, [14][15][16] our original intent was to use the Dieckmann condensation [17] on an Ugi adduct to access tetramic acids (pyrrolidine-2,4-diones;S cheme 1).…”