Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Visible-Light Photoredox-Catalyzed Decarboxylative Alkylation of Heteroarenes Using Carboxylic Acids with Hydrogen Release Wan-Fa Tian,†,‡,§ Chun-Hong Hu,†,§ Ke-Han He,† Xiao-Ya He,† and Yang Li*,† †
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Center for Organic Chemistry, Frontier Institute of Science and Technology and State Key Laboratory for Mechanical Behavior of Materials, Xi’an Jiaotong University, Xi’an, Shaanxi 710054, P. R. China ‡ Institute of Organic Chemistry, Jiangxi Science & Technology Normal University, Key Laboratory of Organic Chemistry, Nanchang, Jiangxi 330013, P. R. China S Supporting Information *
ABSTRACT: Herein, we have developed visible-light photoredox-catalyzed decarboxylating carboxylic acids for alkylation of heteroarenes under mild conditions. The transformation occurred smoothly without the requirement of stoichiometric oxidants in the presence of 0.3 equiv of base, which benefited from the release of hydrogen (H2) and carbon dioxide (CO2). Various substrates and functional groups were tolerated. Primary mechanistic studies suggest that an oxidative quenching pathway and a reductive quenching pathway are both possible in the catalytic cycle.
C
decarboxylative alkylation of N-heteroarenes by applying comparatively complex redox-active carboxylic esters, such as N-hydroxyphthalimide esters, as starting materials was also developed (Scheme 1, eq 2).6d,7 Moreover, an additional step was required for transformation of the carboxylic acids to the corresponding carboxylic esters. H2 release coupling reactions demonstrate a nearly 100% atom economy for constructing various chemical bonds without stoichiometric oxidants.8 Very recently, Ackermann and co-workers achieved decarboxylative C−H functionalization of azoles under oxidant-free conditions by visible-light photoredox catalysis with H2 release (Scheme 1, eq 3). However, with 3 equiv of K2HPO4 as a base, only adamantane carboxylic acid was reported.9 We are interested in H2 release transformations,10 including H2 release with CO2 release by photoredox catalysis11 as stoichiometric oxidants, and bases could be avoided. Meanwhile, the carboxylic acid group could be utilized as a regioselective group. Until now, employing this strategy for decarboxylative cross-coupling reactions has been rare.1u With respect to Minisci-type reactions, a pioneering work of trifluoromethylation of (hetero)arenes with TFA under UV light irradiation was reported by Su and Li.12 Later, Zeng reported an elegant electrocatalytic decarboxylative Minisci acylation with α-keto acids.13 Herein, we report decarboxylating carboxylic acids for alkylation of heteroarenes with H2 release by visible-light photoredox catalysis under mild conditions. More than stoichiometric oxidants were avoided. Diverse alkylations of various heteroarenes were achieved with 0.3 equiv of n-Bu4NOAc by taking advantage of CO2 release (Scheme 1, eq 4).
arboxylic acids are comparatively stable, nontoxic, and readily available from natural resources. Utilization of carboxylic acids as starting materials for decarboxylative transformations has been booming in recent decades.1 Meanwhile, Minisci reactions2 have attracted wide attention for functionalization of heterocycles, which are prevalent structural motifs in bioactive natural products and synthetic pharmaceuticals.3 Decarboxylative alkylation of heteroarenes with carboxylic acids was developed in the 1970s by Minisci (Scheme 1, eq 1).4 As visible-light photoredox catalysis has Scheme 1. Decarboxylative Minisci C−H Alkylation of Heteroarenes
been developed as a powerful tool in organic transformations,5 visible-light photoredox-catalyzed decarboxylating carboxylic acids for alkylation of heteroarenes was recently reported by the groups of Glorius and others (Scheme 1, eq 1).4c,6 However, these elegant approaches required more than stoichiometric oxidants, such as persulfates. Furthermore, more than the stoichiometries of additives, such as TFA, Na2HPO4·12H2O, or Cs2CO3, were usually needed. Thus, comparatively lower functional group tolerance and vast wastes were caused. In addition, visible-light photoredox-catalyzed © XXXX American Chemical Society
Received: July 21, 2019
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DOI: 10.1021/acs.orglett.9b02539 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
Bu4OAc (0.3 equiv) as a base under blue LED irradiation, various solvents were investigated (Table 1, entries 1−5). To our delight, the desired product 3aa was obtained in 64% yield in ethyl acetate (EtOAc) (Table 1, entry 5). No product or inferior yield was observed in other solvents of CH3CN, MeOH, DCM, and 1,4-dioxane (Table 1, entries 1−4). Subsequently, the effect of other cobalt catalysts was tested (Table 1, entries 6−8). [Co(dmgH)2Py2]PF6 induced higher reaction efficiency (Table 1, entry 8). The influence of other bases of CsOAc, CsF, and DABCO was also examined (Table 1, entries 9−11). n-Bu4NOAc displayed the higher yield, which should be attributed to its better solubility. Other photosensitizers of Ru(bpy)3Cl2(EPC*/PC− = +0.77 V vs SCE),5a Acr+-Mes ClO4(EPC*/PC− = +2.06 V vs SCE),16 and 4CzlPN (EPC*/PC− = +1.35 V vs SCE)17 showed no catalytic activities, although there are possibilities of oxidating the adamantyl anion (AdCO2−) to an adamantyl radical (AdCO2•) based on the redox potential analysis (EAdCOO•/AdCOO− = +0.79 V vs SCE) (Table 1, entries 12−14).18 Reducing the amounts of the photosensitizer and the cobalt catalyst gave lower yields (Table 1, entries 15 and 16). Finally, 92% isolated yield was obtained by prolongation of the reaction time to 30 h (Table 1, entry 18). Control experiments proved that a photosensitizer, a cobalt complex, a base, and visible-light irradiation were essential (Table 1, entries 20−23). The yields of H2 and CO2 were consistent with that of the products in most cases. In the
The designed decarboxylative alkylation of heteroarenes would initiate generation of an alkyl carboxylic radical via visible-light redox catalysis with a catalytic base, which is followed by decarboxylation to generate an alkyl radical. The resulting alkyl radical nucleophilically attacks the heteroarene to afford the desired product by H2 release. One of the competitive pathways is hydrodecarboxylation by the generated alkyl radical.1k Meanwhile, the presence of cobalt complexes as the H 2 release catalysts would induce dehydrogenative decarboxyolefination to form alkenes as another competitive pathway (Scheme 2).1v,z,aa Scheme 2. Designed and Competitive Pathways
With these considerations in mind, we commenced our study by selecting benzothiazole (1a) and 1-adamantane carboxylic acid (2a, AdCO2H) as the model substrates (Table 1). By applying Ir[dF(CF3)ppy](dtbbpy)PF614 as a photosensitizer, Co(dmgH)2PyCl15 as a H2 release catalyst, and nTable 1. Optimization of the Reaction Conditionsa
entrya
photosensitizer (PS)
[Co]
solvent
H2 (%)
CO2 (%)
3aa (%)
1 2 3 4 5 6 7 8 9b 10c 11d 12 13 14 15e 16f 17g 18h 19h,k 20l 21 22 23m
Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ru(bpy)3Cl2 Acr+-Mes ClO4− 4CzlPN Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy ― Ir[dF(CF3)ppy]2dtbbpy Ir[dF(CF3)ppy]2dtbbpy
Co(dmgH)2PyCl Co(dmgH)2PyCl Co(dmgH)2PyCl Co(dmgH)2PyCl Co(dmgH)2PyCl Co(dmgH)2(4-NMe2Py)Cl Co(dmgH)2(4-CO2NMe2Py)Cl [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 [Co(dmgH)2Py2]PF6 ― [Co(dmgH)2Py2]PF6
CH3CN MeOH DCM 1,4-dioxane EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc/CH3CN EtOAc EtOAc EtOAc EtOAc
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