Visible-Light-Mediated [4+2] Annulation of N-Cyclobutylanilines with Alkynes Catalyzed by Self-Doped Ti3+ @TiO2

Abstract

We herein report a visible-light-mediated heterogeneous [4+2] annulation of N-cyclobutylanilines with alkynes catalyzed by self-doped Ti³⁺ @TiO₂ . The self-doped Ti³⁺ @TiO₂ is stable under photooxidation conditions, easy to recycle, and can be used multiple times without appreciable loss of activity. Extensive mechanistic studies suggest that the annulation reaction is mediated by singlet oxygen, which is generated through the photosensitization of oxygen in the air by the self-doped Ti³⁺ @TiO₂ . In contrast, the homogeneous variant catalyzed by a far more expensive iridium complex proceeds under an inert atmosphere, which indicates a different mechanism. The substrate scopes of the two processes are comparable.

Keywords: annulation; cyclobutylaniline; photocatalysis; singlet oxygen; titanium; visible light.

Figure 1

Catalyst Recycle.

Figure 2

TEM Images of Self-doped Ti³⁺@TiO₂ before Reactions.

Figure 3

TEM Images of Self-doped Ti³⁺@TiO₂ after 5 Runs.

Figure 4

EPR Study. A). Trapping of ¹O₂ generated from Ti³⁺@TiO₂ by TEMP without cyclobutylaniline 1a. B). Trapping of ¹O₂ generated from Ti³⁺@TiO₂ by TEMP with cyclobutylaniline 1a. C). Control: Trapping of ¹O₂ Generated by Visible Light Irradiation without Ti³⁺@TiO₂.

Figure 4

EPR Study. A). Trapping of ¹O₂ generated from Ti³⁺@TiO₂ by TEMP without cyclobutylaniline 1a. B). Trapping of ¹O₂ generated from Ti³⁺@TiO₂ by TEMP with cyclobutylaniline 1a. C). Control: Trapping of ¹O₂ Generated by Visible Light Irradiation without Ti³⁺@TiO₂.

Figure 5

Fluorescence Spectra of SOSG in the Presence of Self-Doped Ti³⁺@TiO₂ with light, without light, or in the Absence of Self-Doped Ti³⁺@TiO₂.

Scheme 1

[4+2] Annulation of N-Cyclobutylanilines with Alkynes.

Scheme 2

Oxidation of Primary Amines to Imines on UV-irradiated TiO₂.

Scheme 3

Proposed Catalytic Cycle for the [4+2] Annulation Catalyzed by Self-doped Ti³⁺@TiO₂.

Scheme 4

Chemical Probes for the Involvement of ¹O₂ and Radical Intermediates.

Scheme 5

Comparison of Self-doped Ti³⁺@TiO₂ against Rose Bengal.

Chart 1

Substrate Scope of the [4+2] Annulation Catalyzed by Self-doped Ti³⁺@TiO₂^a,b [a] Reaction condition: substrate 1 (0.2 mmol, 0.1 M in ^tBuOH), 2 (0.6 mmol), T3 (2 mg, 10 mol%), irradiation with two 18 W white LED light bulbs. [b] Isolated yield after silica gel chromatograph.