"Canopy Catalysts" for Alkyne Metathesis: Molybdenum Alkylidyne Complexes with a Tripodal Ligand Framework

Abstract

A new family of structurally well-defined molybdenum alkylidyne catalysts for alkyne metathesis, which is distinguished by a tripodal trisilanolate ligand architecture, is presented. Complexes of type 1 combine the virtues of previous generations of silanolate-based catalysts with a significantly improved functional group tolerance. They are easy to prepare on scale; the modularity of the ligand synthesis allows the steric and electronic properties to be fine-tuned and hence the application profile of the catalysts to be optimized. This opportunity is manifested in the development of catalyst 1f, which is as reactive as the best ancestors but exhibits an unrivaled scope. The new catalysts work well in the presence of unprotected alcohols and various other protic groups. The chelate effect entails even a certain stability toward water, which marks a big leap forward in metal alkylidyne chemistry in general. At the same time, they tolerate many donor sites, including basic nitrogen and numerous heterocycles. This aspect is substantiated by applications to polyfunctional (natural) products. A combined spectroscopic, crystallographic, and computational study provides insights into structure and electronic character of complexes of type 1. Particularly informative are a density functional theory (DFT)-based chemical shift tensor analysis of the alkylidyne carbon atom and ⁹⁵Mo NMR spectroscopy; this analytical tool had been rarely used in organometallic chemistry before but turns out to be a sensitive probe that deserves more attention. The data show that the podand ligands render a Mo-alkylidyne a priori more electrophilic than analogous monodentate triarylsilanols; proper ligand tuning, however, allows the Lewis acidity as well as the steric demand about the central atom to be adjusted to the point that excellent performance of the catalyst is ensured.

Figure 1

Prototype of the canopy catalysts and the parent triphenylsilanolate complexes; modulation of the donor properties of a silanolate ligand caused by the facile bending and stretching of the Mo–O–Si angle.

Scheme 1. Current State of the Art: Triarylsilanolate Catalysts That Tolerate Diverse Functionality and Complex Settings but Fail with Simple Unhindered Alcohols

Complex 2 was released in situ from the corresponding ate complex chosen as precatalyst, cf. ref (17c).

Scheme 2. Previous Attempts to Prepare Molybdenum Alkylidyne Complexes with a Podand Ligand Architecture^,

Scheme 3. Ligand Synthesis

Reagents and conditions: (a) SiCl₄, EtOH, 0 °C → RT, 90% (X = H, 20 g scale); (b) TfOH, 130 °C, 55% (X = F); (c) tBuLi, Et₂O, R₂Si(OMe)₂, −125 °C → RT, 75% (9a), 86% (9b), 12% (9c); (d) tBuLi, Et₂O, R₂SiH(Cl), −125 °C → RT, 91% (10d), 81% (10e); (e) aq. HCl, 0 °C → RT, quant. (11a, 5 g scale), 78% (11b), quant. (11c); (f) mCPBA, 94% (11d in CH₂Cl₂), 81–87% (11e, in tetrahydrofuran (THF)); (g) tBuLi, Et₂O, benzophenone, −125 °C → RT, 78% (2 g scale).

Figure 2

Structure of compound 11e in the solid state (only one of the two independent molecules in the unit cell is shown). Hydrogen atoms except for the −OH protons are not shown for clarity. The red lines indicate hydrogen bonds.

Figure 3

Structure of compound 12 in the solid state. Cocrystallized CH₂Cl₂ and hydrogen atoms (except for the −OH protons) are not shown for clarity. The red lines indicate hydrogen bonds.

Scheme 4. Preparation of the Catalysts

Reagents and conditions: (a) see ref (4); (b) NaOtBu, THF, 83%; (c) 11, toluene, 95% ([1a]₂), 50% ([1b]₂, 76% ([1c]₂); (d) toluene, 60 °C, see text; (e) MeCN, quant. (NMR), see text.

Scheme 5. Carbinol Variant

Figure 4

Structure of complex of [2a]₂ in the unit cell. All H atoms except for the ortho-protons of the benzylidyne units are omitted for clarity. The red lines indicate the close interactions of these H atoms with neighboring phenyl rings of the silanolate ligands, indicative of C–H/π interactions. The packing reveals numerous intermolecular π/π and C–H/π interactions between the two independent molecules of this dimeric aggregate. Color code: Mo = yellow, O = red, Si = green, and C = black.

Scheme 6. Additional Catalysts

Reagents and conditions: (a) 11e, toluene, 99%; (b) 11d, toluene; (c) 11a, toluene, 65%; (d) 11d, toluene, 84%.

Figure 5

Representation of the truncated structure of complex 1e in the solid state, in which the lateral phenyl rings on silicon were removed to unveil the almost linear benzylidyne unit and the compressed array of the core, which clearly deviates from an ideal tetrahedral geometry; see text. Hydrogen atoms are omitted for clarity. For the full structure, see the Supporting Information.

Figure 6

Structure of complex 1d in the solid state. Hydrogen atoms are omitted for clarity.

Figure 7

LUMO of complex 1e.

Figure 8

⁹⁵Mo NMR spectra of the monomeric canopy complexes 1a and 1e differing only in the aryl substituent on the alkylidyne. The spectra were recorded at 60 °C.

Figure 9

⁹⁵Mo NMR spectra of different complexes (all in monomeric form) bearing the same aryl substituent on the alkylidyne. All spectra were recorded at 60 °C; Ar = p-MeOC₆H₄.

Figure 10

Three relevant orbital couplings.

Figure 11

CST analysis of complexes 1e and 2b.

Scheme 7. Discrete Intermediates Downstream from the Molybdenum Alkylidynes

Figure 12

Benchmarking experiment (¹H NMR): consumption of 1-methoxy-4-(prop-1-yn-1-yl)benzene (19) ([D₈]-toluene, 0.1 M, 27 °C, 5 mol % catalyst loading). The inset shows that the reaction catalyzed by 1f had reached equilibrium in <5 min, when the second data point was recorded.

Scheme 8. Positive Impact of the Chelate Effect

Scheme 9. Homo-Metathesis Reactions of Substrates Comprising C–H and/or N–H Acidic Sites

The reactions were performed with 1a (5 mol %) in toluene at RT in the presence of MS 5 Å. At 90 °C with 10 mol % of catalyst.

Scheme 10. Survey of the Functional Group Tolerance: Homo-Metathesis Reactions

The choice of catalyst is color-coded; at 60 °C. At 90 °C; NR = no reaction

Scheme 11. Ring-Closing Alkyne Metathesis (RCAM): Test Reactions

Unless stated otherwise, all reactions were performed with 1a (5 mol %) in toluene in the presence of powdered MS 5 Å at ambient temperature. At 60 °C.

Scheme 12. Formation of Key Intermediates of Previous Natural Product Total Syntheses

Reagents and conditions: (a) 1a (5 mol %), toluene, MS 5 Å, RT, quant.; (b) 1a (5 mol %), toluene, MS 5 Å, 60 °C, 75%; (c) 1a (5 mol %), toluene, MS 5 Å, RT, 85%; (d) 1f (30 mol %), toluene, MS 5 Å, 80 °C, 81%.