Photoinduced Heterogeneous C−H Arylation by a Reusable Hybrid Copper Catalyst

Abstract Heterogeneous copper catalysis enabled photoinduced C−H arylations under exceedingly mild conditions at room temperature. The versatile hybrid copper catalyst provided step‐economical access to arylated heteroarenes, terpenes and alkaloid natural products with various aryl halides. The hybrid copper catalyst could be reused without significant loss of catalytic efficacy. Detailed studies in terms of TEM, HRTEM and XPS analysis of the hybrid copper catalyst, among others, supported its outstanding stability and reusability.

We initiatedo ur studies by probing representative reaction conditions for the envisioned CÀHa rylation of heteroarenes by using tailor-made, silica-supportedh ybrid copperc atalyst (Table 1). [19] Thus, the desired CÀHa rylated product 3aa was obtained with the reusable hybrid copperc atalyst under mild photoinduced conditions (entry 1). The sole use of copper iodide fell short in efficiently delivering the desired product (entry 2). Controle xperiments verified the essential role of the Hybrid-Cu catalyst(entries 3-5).
With the optimal reaction conditions in hand, we explored the versatility of the hybrid copper catalysis fort he photoinduced CÀHa rylation of thiazoles 1 or oxazoles 4 with diversely substituted aryl iodides 2 (Scheme1). Thus, the robusth ybrid copperc atalyst smoothly enabled the photoinduced CÀHa rylation with high functional group tolerance, featuring electronrich and electron-deficient aryl halides 2,i ncluding sensitive aryl chlorides and bromides. The photoinduced CÀHa rylation of azoles occurred with high levels of site selectivity,e xclusively delivering C2 arylated products.
Interestingly,t he photoinduced heterogeneous CÀHa rylation manifold was not restricted to the functionalizations of aryl iodides 2,b ut more cost-effective aryl bromides 8 were also identified as suitable substrates under slightly modified conditions (Scheme 3). [19] Thereby,a ryl bromides 8 bearing electron-rich and electron-deficient functional groups were fully tolerated by the heterogeneous photocatalysis. The robustnesso ft he photoinduced CÀHa rylation by the hybrid copperc atalystw as reflected by mild ands ustainable catalysis.
Thereafter,w ep erformed mechanistic studies to rationalize the mode of action of the hybrid catalyst. [19] To this end, an intermolecular competition experiment revealed that the electron-deficient aryl iodide 2e underwent faster directa rylation, being suggestive of the oxidative addition the aryl halide onto the copper(I) intermediate to be rate-determining (Scheme 4a). [21] Furthermore, we probed aS ET-type regime (SET = single-electront ransfer) by the representative radical scavenger 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO), resulting in as ignificant inhibition of the photoinduced hybrid copperc atalysis for CÀHa rylation (Scheme 4b). As toichiometric reactionw ith well-defined copper(I) complex 8 furtherr eflected the importance of the CÀHa rylation step in the photoinduced CÀHa rylation (Scheme 4c).
Finally, we testedt he photoinduced CÀHa rylation by on-off experiments, highlighting that the Hybrid-Cu-catalyzed CÀHa rylation is fully suppressed in the absence of light, ands howing that constant irradiation is required for effective product formation( Scheme 5). [22] Aq uantum yield of 12 %w as determined,t hus rendering ar adical chain reaction unlikely to be of relevance. [19] Additionally,w em onitored the conversion profile of the photoinduced CÀHa rylation by Hybrid-Cu catalyst. [19] Considering the efficacy of the versatile and robustp hotoinduced CÀHa rylation by the hybrid copper catalyst, we became intrigued to probe its potentialr eusable nature. [19] We were hence delighted to observe that the Hybrid-Cu featured reusability,p roviding facile access to the alkaloid naturalp roduct texamine 5hb (Scheme6). [23] It is worth noting that less than 4ppm of copperw as detected by detailedi nductivelyc oupled plasma optical emission spectrometry (ICP-OES) analysis of the reactionmixture, reflecting negligible leaching of the transition metal.
Scheme4.Key mechanistic studies.a )Competition experiment. b) Probing an SET-type mechanism by TEMPO scavenger.c)Stoichiometricreaction with copper complex 8.
Given the unique features of the reusable hybrid copperc atalyst, we intended to determine its morphological anda tomic properties (Figure 2). [19] To this end, we performed detailed transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM) studies of SBA-15, the Hybrid-Support, Hybrid-Cu and the reused Hybrid-Cu. TEM images of the SBA-15a nd the Hybrid-Support showed homogenously orderedm esoporous structures (Figure 2a,I -VI).
HRTEM and TEM images of Hybrid-Cua nd of the reused Hybrid-Cud elineated highly ordered one-dimensional mesoporous channels withoutm orphological agglomeration (Figure 2a,V II-XII), [24] indicating outstanding reusability and stability of hybrid copperc atalyst for photoinducedC ÀHa rylation. Subsequently,X -ray photoelectrons pectroscopy (XPS)s tudies indicated that both Hybrid-Cu and the reused Hybrid-Cu are copper(I) species, based on Cu 2p 3/2 and Cu LMM-Augerp eaks (Figure 2b). [25] On the basis of our detailed mechanistic studies and the characterization of the hybrid copper catalyst, ap lausible catalytic cycle for the photoinduced heterogeneous CÀHa rylation was proposed (Scheme 8). The mechanism rationale commences with hybrid copper(I) catalysta nd benzothiazole, forming copper complex A by the aid of ab ase. Irradiation of copper complex A leads to ap hotoexcited state B,f ollowed by aS ET Scheme6.Reuse of the hybrid copper catalystfor photoinducedC ÀHa rylation.
In summary,w eh ave reportedaphotoinduced CÀHa rylation by heterogeneous copperc atalysis under exceedingly mild reactionc onditions at room temperature. [26] The modular hybrid copper catalyst featured remarkable catalytic power towards site-selective CÀHa rylations with ample scope. The heterogeneous catalyst was reusablew ithout significant loss of catalytic efficacy.M echanistic studies showeds trong evidence for photoinduced, excited-state copper catalysis enabled by a reusableh ybrid regime. Detailed microscopica nd spectroscopic analysis illustrated excellentp hysicala nd chemical stability of the hybrid copper catalystf or photoinduced CÀHa rylation, providing ag ood agreement with experimental studies.