Preparation of Butadienylpyridines by Iridium-NHC-Catalyzed Alkyne Hydroalkenylation and Quinolizine Rearrangement

Abstract

Iridium(I) N-heterocyclic carbene complexes of formula Ir(κ² O,O'-BHetA)(IPr)(η² -coe) [BHetA=bis-heteroatomic acidato, acetylacetonate or acetate; IPr=1,3-bis(2,6-diisopropylphenyl)imidazolin-2-carbene; coe=cyclooctene] have been prepared by treating Ir(κ² O,O'-BHetA)(η² -coe)₂ complexes with IPr. These complexes react with 2-vinylpyridine to afford the hydrido-iridium(III)-alkenyl cyclometalated derivatives IrH(κ² O,O'-BHetA)(κ² N,C-C₇ H₆ N)(IPr) through the iridium(I) intermediate Ir(κ² O,O'-BHetA)(IPr)(η² -C₇ H₇ N). The cyclometalated IrH(κ² O,O'-acac)(κ² N,C-C₇ H₆ N)(IPr) complex efficiently catalyzes the hydroalkenylation of aromatic and aliphatic terminal alkynes and enynes with 2-vinylpyridine to afford 2-(4R-butadienyl)pyridines with Z,E configuration as the major reaction products (yield up to 89 %). In addition, unprecedented (Z)-2-butadienyl-5R-pyridine derivatives have been obtained as minor reaction products (yield up to 21 %) from the elusive 1Z,3gem-butadienyl hydroalkenylation products. These compounds undergo a thermal 6π-electrocyclization to afford bicyclic 4H-quinolizine derivatives that, under catalytic reaction conditions, tautomerize to 6H-quinolizine to afford the (Z)-2-(butadienyl)-5R-pyridine by a retro-electrocyclization reaction.

Keywords: C−C coupling; C−H activation; N-heterocyclic carbenes; catalysis; hydroalkenylation; iridium.

Scheme 1

Synthetic strategies for the preparation of butadienylpyridines.

Scheme 2

Preparation of Ir(κ² O,O’‐BHetA)(IPr)(η ²‐coe) complexes.

Figure 1

ORTEP plot of Ir(κ² O,O’‐acac)(IPr)(η ²‐coe) (3) with ellipsoids at 50 % probability. For brevity only one of the two molecules in the asymmetric unit is shown, the other being similar (Figure S29 in the Supporting Information). Most hydrogen atoms are omitted for clarity, and a wireframe style is adopted for the 2,5‐(iPr)₂C₆H₃ moiety of the IPr ligand. Selected bond lengths [Å] and angles [°] are: C1‐Ir1 1.9419(17), C30‐C31 1.417(2), O38‐Ir1 2.0686(13), O42‐Ir1 2.0706(12), Ir1‐CT01 1.97648(9), O38‐Ir1‐O42 88.32(5), C1‐Ir1‐CT01 94.27(5), C1‐Ir1‐O38 84.67(16). CT01 is the centroid of C30 and C31.

Scheme 3

Reactivity of Ir(κ² O,O’‐BHetA)(IPr)(η ²‐coe) complexes with 2‐vinylpyridine.

Figure 2

ORTEP plot of Ir(κ² O,O’‐acac)(IPr)(η ²‐C₇H₇N) (5) with ellipsoids at 50 % probability. Most hydrogen atoms are omitted for clarity, and a wireframe style is adopted for the 2,6‐(iPr)₂C₆H₃ moiety of the IPr ligand. Selected bond lengths [Å] and angles [°] are: Ir−C1 1.955(2), Ir−CT01 1.98530(12), Ir−O34 2.0469(17), Ir−O30 2.0644(16), C37‐C38 1.418(4), O34‐Ir−O30 89.20(7), C1‐Ir−CT01 93.10(7). CT01 is the centroid of C37 and C38. C1‐N2‐C3‐C4‐N5: pitch angle (θ) 7.1°, yaw angle (ψ) 3.5°.

Figure 3

ORTEP view of IrH(κ² O,O’‐acac)(κ² N,C‐C₇H₆N)(IPr) (6, top), and IrH(κ² O,O’‐OAc)(κ² N,C–C₇H₆N)(IPr) (7, bottom) with ellipsoids at 50 % probability. For clarity most hydrogen atoms are omitted and wireframe style is adopted for the 2,6‐(iPr)₂C₆H₃ moiety of the IPr ligand. For brevity only one of the two complexes of the asymmetric unit of 7 is shown, the other being similar (Figure S31). Selected bond lengths (Å) and angles (°) are: 6, C1‐Ir 1.990(3), C37‐Ir 1.977(3), Ir−H 1.587(10), N30‐Ir 2.105(3), O38‐Ir 2.176(2), O42‐Ir 2.149(2), C1‐Ir−H 87.0[14], O42‐Ir−O38 86.69(9), C37‐Ir−N30 79.21[13]; 7, C1‐Ir1 1.983(3), C37‐Ir1 1.956(3), N30‐Ir1 2.084(3), O38‐Ir1 2.283(2), O40‐Ir1 2.243(2), Ir1‐H1 1.589(10), C1‐Ir1‐H1 81.8[15], O40‐Ir1‐O38 57.91(9), C37‐Ir1‐N30 79.12[13].

Figure 4

¹H NMR spectra of 5 and 6 and ¹H‐¹H NOE correlations for the hydride ligand of 6.

Figure 5

Selected region of the ¹H NMR spectra (CDCl₃) of 2‐{(1Z,3E)‐4‐phenylbuta‐1,3‐dien‐1‐yl}pyridine (9  a) and (Z)‐2‐(buta‐1,3‐dien‐1‐yl)‐5‐phenylpyridine (10  a) along with the proposed assignment.

Scheme 4

Proposed mechanism for the hydroalkenylation of alkynes with 2‐vinylpyridine leading to 9.

Scheme 5

Deuterium‐labeling experiment: hydroalkenylation of [D]phenylacetylene with 2‐vinylpyridine catalyzed by 6.

Scheme 6

Proposed mechanism for the formation of 10 in the hydroalkenylation of phenylacetylene with 2‐vinylpyridine catalyzed by 6.

Scheme 7

Proposed sequence for the formation of 10  a along with the relative Gibbs free energy of the intermediates (italics, kcal mol⁻¹) under metal‐free conditions.