A Mixed-Valence Ti(II)/Ti(III) Inverted Sandwich Compound as a Regioselective Catalyst for the Uncommon 1,3,5-Alkyne Cyclotrimerization

Abstract

The synthesis, structure, and catalytic activity of a Ti(II)/Ti(III) inverted sandwich compound are presented in this study. Synthesis of the arene-bridged dititanium compound begins with the preparation of the titanium(IV) precursor [TiCl₂(^MesPDA)(thf)₂] (^MesPDA = N,N'-bis(2,4,6-trimethylphenyl)-o-phenylenediamide) (2). The reduction of 2 with sodium metal results in species [{Ti(^MesPDA)(thf)}₂(μ-Cl)₃{Na}] (3) in oxidation state III. To achieve the lower oxidation state II, 2 undergoes reduction through alkylation with lithium cyclopentyl. This alkylation approach triggers a cascade of reactions, including β-hydride abstraction/elimination, hydrogen evolution, and chemical reduction, to generate the Ti(II)/Ti(III) compound [Li(thf)₄][(Ti^MesPDA)₂(μ-η⁶: η⁶-C₆H₆)] (4). X-ray and EPR characterization confirms the mixed-valence states of the titanium species. Compound 4 catalyzes a mild, efficient, and regiospecific cyclotrimerization of alkynes to form 1,3,5-substituted arenes. Kinetic data support a mechanism involving a binuclear titanium arene compound, similar to compound 4, as the resting state. The active catalyst promotes the oxidative coupling of two alkynes in the rate-limiting step, followed by a rapid [4 + 2] cycloaddition to form the arene product. Computational analysis of the resting state for the cycloaddition of trimethylsilylacetylene indicates a thermodynamic preference for stabilizing the 1,3,5-arene within the space between the two [Ti^MesPDA] fragments, consistent with the observed regioselectivity.

Figure 1

a) Mechanism for the cyclotrimerization of alkynes. b) Reported low-valent titanium–arene compounds.

Scheme 1. Synthesis of Compounds. a) 2, b) 3, and c) 4

Figure 2

Solid-state structure of compound 2 with ellipsoids at 30% of probability. Hydrogen atoms are omitted for clarity. The dihedral angle between planes formed by N1–Ti1–N2 and N1–C1–C2-N2 is 14.1°. Selected average bond distances (Å) and angles (°): Ti–N 1.970(5), Ti–O 2.208(1), Ti–Cl 2.364(9), N–Ti–N 80.48(9), O–Ti–O 95.1(1), Cl–Ti–Cl 162.08(3).

Figure 3

Solid-state structure of compound 3 with ellipsoids at 30% of probability. Hydrogen atoms are omitted for clarity. Selected average bond distances (Å) and angles (°): Ti–N 2.01(1), Ti–O 2.139(8), Ti–Cl 2.53(5), Na–Cl 2.78(1), Na-centroid 2.589(3) and 2.644(3), O2–Ti1–Cl2 163.07(7), N1–Ti1–N2 80.4(1), Cl1–Ti1–Cl3 84.81(3), Cl1–Ti2–N4 175.41(8), O1–Ti2–N3 102.0(2), Cl2–Ti2–Cl3 77.63(3).

Figure 4

Solid-state structure of compound 4 with ellipsoids at 30% of probability. Hydrogen atoms, except those of the benzene ring, are omitted for clarity. Selected average bond distances (Å) and angles (°): Ti–N 2.014(4), Ti–C 2.23(5), C–C 1.451(4), Ti-centroid 1.691(3), N–Ti–N 78.63(6).

Figure 5

Computed reaction profile for the formation of 4 from A. Relative free energies (at 298 K) are given in kcal/mol. The computed spin density in 4 is also depicted and shows that the unpaired electron is equally distributed on both titanium atoms (0.54 e). All data were computed at the M06L/def2-SVP level.

Scheme 2. Proposed Mechanism for the Formation of Compound 4

Scheme 3. Mechanism for the Cyclotrimerization of Alkynes Catalyzed by Compound 4

Figure 6

DFT-modeled compounds similar to 4 with tris(trimethylsilyl)benzene as a bridging fragment. All data have been computed at the M06L/def2-SVP level.