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Article Cite This: ACS Omega 2018, 3, 1983−1990
Empowering Transition-Metal-Free Cascade Protocol for the Green Synthesis of Biaryls and Alkynes Preet Kamal Walia, Manoj Kumar, and Vandana Bhalla* Department of Chemistry, UGC Sponsored Centre for Advanced Studies-II, Guru Nanak Dev University, Amritsar 143005, Punjab, India S Supporting Information *
ABSTRACT: The work being presented in this paper demonstrates the simple and efficient “transition-metal-free” and “light-mediated” synthetic protocol for the synthesis of aryl iodides/biaryls/alkynes from aryl bromides. Under ultraviolet irradiation and in basic aqueous media, aryl bromides undergo transformation into aryl iodides which efficiently couple via a cascade reaction with a wide range of terminal alkynes/unactivated arenes to generate target molecules under green conditions.
1. INTRODUCTION Biaryl compounds are essential precursor materials for the preparation of compounds having diverse industrial and pharmaceutical applications.1a,b Till date, transition-metalcatalyzed direct arylation of C−H bond is the best approach for the synthesis of biaryl derivatives.2a−d Although this approach is highly efficient, utilization of catalytic systems based on costly and toxic metal ions raises serious economic and environmental issues. Further, separation of the target molecule from the metal-based catalytic system is timeconsuming and a costly process. Thus, efforts are in progress to develop an economic and ecofriendly “transition-metal-free” strategy for the preparation of biaryl targets via cross-coupling of unactivated arenes and aryl halides. Recently, various “transition-metal-free” protocols have been reported which involve utilization of a variety of ligands such as phenanthroline, 1,2-dimethylethylenediamine, or nitrogen-containing heterocyclic compounds as additives3a,b in combination with metaltert-butoxide as a base to promote cross-coupling between aryl iodides/bromides and unactivated arenes. Unfortunately, the recyclability of the catalyst in this strategy remains a big task and the high loading of nitrogen-containing compounds decreased the economic and environmental advantages of the strategy. This strategy is still growing, and efforts are in progress to employ visible light to carry out cross-coupling reaction under eco-friendly and economic conditions. Recently, visible-light-mediated synthesis of biaryl targets by using a photosensitive complex of potassium-tert-butoxide (KOtBu) and nitrogenous heterocyclic ligands as a photocatalyst has been reported.4 Further, powerful light sources (two HPI-T 400 W lamps) have been utilized for direct arylation of benzene using dimethyl sulfoxide-solvated KOtBu.5 Although this base © 2018 American Chemical Society
and light-assisted approach for the synthesis of biaryls is economic and environmental friendly, the requirement of excess amount of ligand (50 mol %) necessitates additional efforts for the development of “green” protocol for the synthesis of biaryls. Another problem associated with the “transition-metal-free” synthesis of biaryl derivatives using this approach is regarding one of its starting material, that is, aromatic iodides.6 Most of the reactions involving the preparation of biaryls work best when aromatic iodides are used as one of the coupling partner. Previously, copper- or nickel-catalyzed strategies for the preparation of aryl iodide have been reported; however, these methods suffer from a series of limitations which include limited substrate scope and the requirement for high temperatures (>100 °C).7a−d All of these limitations make the product isolation difficult which increases the overall cost of the synthetic process. Thus, aromatic iodides are needed in abundance, and there is a need for the development of a simple and facile approach for the synthesis of aryl iodides. Recently, the synthesis of complex organic molecules by cascade reaction has emerged as an economic and eco-friendly approach. Cascade reactions initiated by the radical addition are synthetically very attractive because they allow access to molecular skeletons in only one synthetic step under very mild conditions, enabling them to exhibit high functional group compatibility. Additionally, cascade protocol reduces the time of reaction, efforts involved in the reaction setup, and the waste generated by the several chemical processes. Received: December 19, 2017 Accepted: January 23, 2018 Published: February 16, 2018 1983
DOI: 10.1021/acsomega.7b02014 ACS Omega 2018, 3, 1983−1990
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photoheating effect of the UV lamp was prevented by submerging the reaction vial in a water bath. The reaction moved very smoothly in the presence of KI and iodine, and the target product was isolated in 80% yield after completion of the reaction (36 h) (entry 1, Table S1). We then carried the above reaction under argon-free conditions (aerial conditions), and to our surprise, the desired product was isolated in 73% yield in 40 h (entry 2, Table S1). Under aerial atmosphere, the target compound was obtained in slightly lower yield because of the electron capturing ability of oxygen.4 The conversion of bromobenzene (1a) to iodobenzene (2a) in the presence of KI and I2 was then also examined in other solvents such as H2O/ACN (1:1) and H2O (entries 3 and 4, Table S1) under aerial conditions. In all cases, except H2O, yields remained almost same. Therefore, we chose a H2O/ACN (1:1) solvent system for our further studies. The model reaction under visible light irradiation10a and under dark conditions did not proceed (entries 5 and 6, Table S1). Having identified the optimal conditions for the roomtemperature metal-free strategy under the aerial conditions, we next sought to define the scope of the reaction for the preparation of different aryl iodides (Figure 1b and Table S2). The present photocatalytic aromatic Finkelstein reaction displayed a high functional group tolerance (entries 2−7, Table S2) and proved to be a general method for the preparation of aryl iodides in good yields (up to 70%) under very mild conditions. Electron-releasing as well as electronwithdrawing groups gave the target compounds in good yields. Furthermore, the target molecules were purified by recrystallization9b from organic solvents, and no column chromatography was needed for the purification of final products except compound 2a (for detailed procedure, see Supporting Information). We monitored the reaction between 1-bromo4-nitrobenzene and KI using I2 in H2O/ACN (1:1) using 1H NMR spectroscopy. The sample from the reaction mixture was withdrawn after 14 h, and after usual workup (no purification), 1 H NMR spectrum was recorded. Then, the samples were withdrawn after 24 and 38 h, and the same procedure was repeated to record the 1H NMR spectra. Finally, the reaction was stopped after 52 h. The resulting suspension was quenched with aqueous solution of Na2S2O3. The solution was then extracted with the organic solvent (EtOAc). The EtOAc layer was dried over Na2 SO 4. The organic layer was then concentrated in vacuo and then purified by recrystallization from methanol.9b The stacked spectra of all of the samples show the gradual consumption of 4-bromonitrobenzene and subsequential formation of 4-iodonitrobenzene (Figure S9A,B, Supporting Information). This broad substrate scope of the strategy could be helpful in facilitating the further functionalization of the prepared aryl iodides. Moreover, this procedure for the model reaction, when adapted to the gram-scale reaction, resulted in the formation of the product in 63% yield. To confirm the pathway for the reaction, we performed the model reaction in the presence of (2,2,6,6-tetramethylpiperidin1-yl)oxyl (TEMPO) (a typical radical scavenger) and benzoquinone (another radical scavenger) in the H2O/ACN (1:1) solvent system. Even after 40 h, the conversions did not take place (entries 7 and 8, Table S1). The above control experiments indicate a radical pathway for the aromatic Finkelstein reaction. The mechanism of the photocatalytic aromatic Finkelstein reaction is based on the photoinduced SET from KI to aryl bromides.10a In this mechanism, the transfer of one electron from KI to aryl bromide takes place
Our research work involves the development of new catalytic systems for harvesting solar radiations for carrying out a variety of reactions.8a−c Considering the importance of cascade reaction and the role of UV light in the activation of starting materials, we began by exploring the optimized conditions for biaryl synthesis under “transition-metal-free” conditions starting from aryl iodides. Gratifyingly, we were successful in improving the existing protocol of the UV light-mediated “transitionmetal-free” strategy for the synthesis of aryl iodides from aryl bromides. Furthermore, we were successful in developing the “metal-free” and light-mediated cascade synthetic protocol for the synthesis of alkynes from aryl iodides and terminal alkynes via Sonogashira coupling reaction. As per our knowledge, this is the first report where aromatic Finkelstein reaction/biaryl coupling and aromatic Finkelstein reaction/Sonogashira coupling have been demonstrated in (i) one-pot two-step reaction and (ii) cascade reaction under “transition-metal-free” conditions for the synthesis of biaryls/alkynes, respectively. In this protocol, the product isolation is simple and all of the target molecules were purified by recrystallization from organic solvents, and no column chromatography was needed for the purification of final products.
2. RESULTS AND DISCUSSION The traditional methods for the synthesis of aryl iodides involve treatment of aryl bromides with inorganic halides such as NaI in the presence of high loading of catalytic systems (Figure 1a).9a−c
Figure 1. (a) Previous methods of preparing aryl iodides from aryl bromides. (b) Our photochemical method for synthesizing aryl iodides using UV light.
Our strategy about UV light-mediated aromatic Finkelstein reaction is based on already reported photoinduced singleelectron transfer (SET) from NaI to aryl bromides in acetonitrile (ACN) using UV light under argon.10a,b We envisioned that this electron transfer can also occur under argon-free conditions. Hence, we began our study by carrying out the conversion of aryl bromides to aryl iodides under aerial conditions using potassium iodide (KI) and I2 in ACN. We chose conversion of bromobenzene (1a) to iodobenzene (2a) in ACN as a model reaction under argon (Figure 1b). The 1984
DOI: 10.1021/acsomega.7b02014 ACS Omega 2018, 3, 1983−1990
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Figure 2. (a) Previous methods of preparing biaryls from aryl iodides. (b) Our photochemical method for synthesizing biaryls using direct/one-pot two-step/cascade strategy in the presence of UV light.
We carried out the model reaction between 4-iodoanisole (3d) and benzene (4a) under inert conditions in the presence of UV light under metal-free conditions using KOtBu as a base (Figure 2bi). The desired product (5d) was obtained in good yield (66%) at 30 °C. We found that the use of UV light in the presence of KOtBu enabled the desired C−H arylated product (5d) in 66% yield (entry 1, Table S3) (see Supporting Information). The necessity of the key reaction components (light source and base) was demonstrated through a series of control experiments (entries 1−10, Table S3) (see Supporting Information). The reactions in the dark and under visible light gave the desired product (5d) in a negligible yield (entries 2 and 3, Table S3) (see Supporting Information). Although the amount (61%) of the product remained almost same under the aerial conditions (entry 4, Table S3) (see Supporting Information), no reaction was observed upon exclusion of UV light (entry 5, Table S3) (see Supporting Information). It is clear from the control experiments (entries 1−5, Table S3) (see Supporting Information) that ultraviolet irradiation is essential for this reaction, as no biaryl product was observed without UV light. The cleavage of the Ar−X bond under UV light irradiation, generally, generates the aryl radical in the absence of a metal
upon irradiation with UV light, resulting in the formation of aromatic radical anion species, which undergoes further fragmentation to form an aryl radical and bromide anion. We tested the generation of Br− anion during the reaction by a AgNO3 test. Upon the addition of AgNO3 solution to the reaction mixture, the solid precipitated out. We recorded the powder X-ray diffraction spectra of this solid which clearly indicates the formation of AgBr (Figure S8, Supporting Information).11 Majority of these aryl radicals are trapped by an iodine radical, producing the desired product (Scheme S1, Supporting Information). After developing a “green” protocol for the preparation of aryl halides via aromatic Finkelstein reaction, we aimed at utilizing these aryl halides as starting materials for direct arylation of unactivated arenes for the construction of biaryls via C−H activation. Very recently, 1,10-phenanthrolinemediated synthesis of biaryls has been reported in the presence of visible light under inert conditions, but the use of an excessive amount of 1,10-phenanthroline (50 mol %) is still necessary (Figure 2a).4 Inspired by these results, we envisaged that it might be possible to drive the SET process in biaryl coupling using UV light only. We were particularly interested in carrying out aromatic C−H activation in an atom-economic and waste-free manner. 1985
DOI: 10.1021/acsomega.7b02014 ACS Omega 2018, 3, 1983−1990
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ACS Omega Scheme 1. UV Light-Induced Synthesis of Biaryl Derivatives (5a−r) under Aerial Conditions at 30 °Ca
a
Isolated yields determined after recrystallization.
yield. We also carried out the reaction of 2-bromoiodobenzene (3k) with benzene to give the target product (5r) in moderate yield. Furthermore, the target molecules were purified by recrystallization from organic solvents, and no column chromatography was needed for the purification of final products. Under these optimized conditions, aryl bromides could not furnish the desired products. To gain insight into the mechanism of this transition-metalfree biaryl coupling reaction, the model reaction was carried out in the presence of TEMPO; however, the reaction did not proceed (entry 9, Table S3) (see Supporting Information). However, we were successful in isolating the para-adduct between 4-iodotoluene and TEMPO whose structure was confirmed from 1H NMR spectra (Figure S28, Supporting Information). Similarly, addition of benzoquinone afforded the desired product in negligible yield (entry 10, Table S3) (see Supporting Information). All of these studies clearly suggest that the generated radical species were essential for carrying out UV light-induced biaryl coupling. To understand the regioselectivity of the reaction, we carried out the reaction between 4-iodotoluene (3b) and benzene to yield (5b) which was then purified by recrystallization from methanol. The residual liquid left after the separation of solid from the reaction mixture was subjected to 1H NMR spectroscopy. The 1H NMR spectra of the residual liquid did not suggest the formation of any other compound (Figure S29, Supporting Information). Furthermore, the reaction between 2-
catalyst. The aryl radical is then trapped by the nucleophile to produce the desired product. The presence of a base such as KOtBu is necessary to trigger the reaction by photoinduced electron transfer to ArX.12 We also examined other bases (entries 6−8, Table S3) (see Supporting Information) and replaced KOtBu with K3PO4, NaOH, and KOAc individually; however, an excellent yield was obtained only when KOtBu was used as a base, and almost no product was detected with other bases used. To explore the potential applications of this method, a variety of substituted aromatic iodides (ArI) were examined (Scheme 1). It was observed that electron-donating substituents on the phenyl ring, such as methoxy and methyl groups, promoted the crosscoupling reaction with high efficiency, whereas in the presence of electron-deficient aryl iodides (−NO2, −Br), target compounds were furnished in moderate yields. Various functional groups were found to be compatible, thus suggesting the great potential of this strategy for further transformation of the cross-coupling products. Other arenes with different substituted groups were also tested to demonstrate the wide applicability of this reaction (entries 5i−k and 5n−q, Scheme 1). Under the optimized conditions, arenes such as toluene (4b), anisole (4c), nitrobenzene (4d), fluorobenzene (4e), chlorobenzene (4f), and bromobenzene (4g) could couple with 4-iodotoluene (3b) to give the products (5i−k, n−q) in moderate yield. Additionally, anisole (4c) could also couple with 4-iodoanisole (3d) to give the product (5k) in moderate 1986
DOI: 10.1021/acsomega.7b02014 ACS Omega 2018, 3, 1983−1990
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ACS Omega bromoiodobenzene (3k) and benzene under the optimized conditions resulted in the formation of ortho-(5r) isomer (Figure S30, Supporting Information). The reaction between 4iodotoluene and TEMPO resulted in the formation of parasubstituted adduct (Figure S28, Supporting Information). All of these results support the regioselectivity of biaryl coupling. On the basis of these results, we propose a plausible reaction mechanism, as shown in Scheme S2 (see Supporting Information).13 In the presence of base (KOtBu), aryl halide (3) generates an aryl halide radical [A] via SET process. Addition of benzene afforded radical [B]. With the assistance of KOtBu, deprotonation takes place resulting in the formation of another radical anion [C]. This radical anion then transfers an electron to another molecule of aryl halide (3) (shown in blue), thereby propagating a chain reaction, resulting in the formation of the final direct C−H arylation product (5). After carrying out C−X/C−C bond formation reactions (aromatic Finkelstein reaction and biaryl coupling) successfully in the presence of UV light, we planned to carry out one-pot two-step reaction comprising aromatic Finkelstein reaction and biaryl coupling in sequence, for the synthesis of biaryls (Scheme 2).
Scheme 3. Cascade Reaction for the Synthesis of Biaryl Derivatives (5a−d, h, i−j, n) under Aerial Conditions in the Presence of UV Light
The reaction mixture was then stirred at rt for 40 h in the presence of UV light. The reaction was monitored using TLC (after 40 h, TLC of the reaction mixture matches very well with the standard sample), indicating the formation of aryl iodide (Figure S10a, Supporting Information). The reaction was then continued under UV light irradiation at 30 °C. The formation of the final product was monitored by TLC again (Figure S10b, Supporting Information). When the reactants were consumed (after 72 h), the resulting mixture was diluted with ethyl acetate. The organic layer was concentrated in vacuo and purified by recrystallization from methanol. The structure of the final products (5a−d, h−j, n) was confirmed from 1H NMR studies. Encouraged by these results, we planned to scrutinize the applicability of the UV light for carrying out Sonogashira− Hagihara coupling reaction under aerial conditions. The traditional methods for the synthesis of alkynes involve treatment of aryl halides with terminal alkynes in the presence of base using high loading of catalytic systems at high temperatures14a−c or using transition metals in the presence of visible light (Figure 3a).15a,b Very recently, this coupling has
Scheme 2. One-Pot Two-Step Reaction Comprising Aromatic Finkelstein Reaction and Biaryl Coupling Reaction in Sequence To Synthesize Biaryl Derivatives (5a−d, h) under Aerial Conditions in the Presence of UV Light
First of all, we carried out the aromatic Finkelstein reaction of aryl bromides (1 mmol) (1a−c, e−f) and KI (3 mmol) using iodine (0.2 M in ACN) in ACN/H2O (1:1) at room temperature under aerial conditions in the presence of UV light. The reaction mixture was stirred at room temperature for 40 h in the presence of UV light. The reaction was monitored using TLC (Thin-Layer Chromatography). After the completion of the reaction (after 40 h, TLC of the reaction mixture matches very well with the standard sample), benzene (4 mL) and KOtBu (3 mmol) was charged into the same reaction mixture in the same pot. The formation of the product was monitored by TLC. When the reactants were consumed (after 72 h), the resulting mixture was diluted with ethyl acetate. The organic layer was concentrated in vacuo and purified by recrystallization from methanol. The final products (5a−d, h) were obtained in two steps. The structure of the final products (5a−d, h) was confirmed from 1H NMR studies. To confirm the synthetic route, we isolated one of the intermediates (2e) after partial workup of the reaction mixture (Figure S31, Supporting Information). After carrying out aromatic Finkelstein reaction and biaryl coupling successfully in one-pot two-step reaction in the presence of UV light under aerial conditions, we planned to carry the reaction in single step using a cascade reaction strategy. For this, the reaction vial was charged with aryl bromide (1 mmol) (1a−c, e, g), ACN/H2O (1:1), KI (3 mmol), I2 (0.2 M in ACN), arene (benzene/toluene/anisole/ nitrobenzene) (4 mL), and KOtBu (3 mmol) (all in sequence) under aerial conditions in the presence of UV light (Scheme 3).
Figure 3. (a) Previous methods of preparing alkynes from aryl halides. (b) Our photochemical method for synthesizing alkynes using one-pot two-step and cascade strategy in the presence of UV light.
been reported under transition metal free conditions in water using UV light.16 However, there is no report on the transitionmetal-free cascade/one-pot two-step synthesis of alkynes using Sonogashira−Hagihara coupling. In view of these results, we envisioned that it might be possible to drive the Sonogashira− Hagihara coupling reaction using cascade strategy by UV light only. 1987
DOI: 10.1021/acsomega.7b02014 ACS Omega 2018, 3, 1983−1990
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the presence of UV light (Figure S33, Supporting Information). The reaction mixture was then stirred at rt. for 40 h in the presence of UV light. The reaction was monitored using TLC. After 40 h, the spot of the reaction mixture turned brown in the iodine chamber, indicating the formation of iodobenzene (TLC of the reaction mixture matches very well with the standard sample) (Figure S33a, Supporting Information). The reaction was then continued at 30 °C under UV light irradiation. The formation of the final product (9a) was monitored by TLC again (Figure S33b, Supporting Information). When the reactants were consumed (after 65 h), the resulting mixture was diluted with ethyl acetate. The organic layer was concentrated in vacuo and purified by recrystallization from methanol. The structure of the final product (9a) was confirmed from 1H NMR studies. With the optimized reaction conditions, the generality of the method was investigated and the products are summarized in Scheme 5. The scope of the reaction was explored with respect to the various substituted aryl bromides. As shown in Scheme 5, various functional groups on the aromatic rings displayed good tolerance under the optimized conditions. Aromatic halides with electron-donating or electron-withdrawing groups can react smoothly with phenylacetylene to give the corresponding alkynes in moderate to good yields (entries 9a−9h, Scheme 5). In addition, bromobenzene could also couple with 4ethynylpyridine to give derivative (9g) in 56% yield. Also, the reaction between 3-bromopyridine (8) and phenylacetylene resulted in the formation of derivative (9h) in 55% yield. To understand the regioselectivity of the reaction, we carried out the reaction between bromobenzene and phenylacetylene to yield (9a) which was then purified by recrystallization from methanol. The residual liquid left after the separation of solid from the reaction mixture was subjected to 1H NMR spectroscopy. The 1H NMR spectra of the residual liquid did not suggest the formation of any other compounds (Figure S42, Supporting Information). Furthermore, the reaction between 3bromopyridine (8) and phenylacetylene under the standard conditions resulted in the formation of metaisomer only (9h) (Figure S41, Supporting Information). All of the above experiments show the regioselectivity of sp2−sp couplings.
We planned to carry out one-pot two-step reaction comprising aromatic Finkelstein reaction and Sonogashira coupling reaction in sequence for the synthesis of alkynes (Scheme 4). First of all, we carried out the aromatic Finkelstein Scheme 4. One-Pot Two-Step Reaction Comprising Aromatic Finkelstein Reaction and Sonogashira−Hagihara Coupling in Sequence To Synthesize Alkynes (9a−e) under Aerial Conditions in the Presence of UV Light
reaction between aryl bromides (1 mmol) (1) and KI (3 mmol) using iodine (0.2 M in ACN) in ACN/H2O (1:1) at room temperature under UV light. The reaction mixture was stirred at room temperature for 40 h at room temperature in the presence of UV light under aerial conditions. The reaction was monitored using TLC. After the completion of the reaction (the spot of the reaction mixture turned brown in the iodine chamber after 40 h), phenylacetylene (6) (3 mmol) and KOtBu (3 mmol) were charged into the same reaction mixture in the same pot. The reaction was then continued at 30 °C under UV light irradiation. The formation of the product was monitored by TLC. When the reactants were consumed (after 75 h), the resulting mixture was diluted with ethyl acetate. The organic layer was concentrated in vacuo and purified by recrystallization from methanol. The structure of the final products (9a−e) was confirmed from 1H spectroscopy. To confirm the synthetic route, we isolated the intermediate (2a) after partial workup of the reaction mixture (Figure S32, Supporting Information). After carrying out aromatic Finkelstein reaction and Sonogashira coupling successfully in the one-pot two-step reaction in the presence of UV light under aerial conditions, we planned to carry out the reaction in single step using cascade strategy. For this, we carried out the model reaction using 4bromobenzene (0.05 g, 1 mmol) in ACN/H2O (1:1), KI (3 mmol), I2 (0.2 M in ACN), phenylacetylene (3 mmol) (6), and KOtBu (3 mmol) (all in sequence) under aerial conditions in
Scheme 5. Cascade Reaction for the Synthesis of Alkynes (9a−h) under Aerial Conditions in the Presence of UV Lighta
a
Isolated yields determined after recrystallization. 1988
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P.; Wang, L.; Li, H. Application of recoverable nanosized palladium(0) catalyst in Sonogashira reaction. Tetrahedron 2005, 61, 8633−8640. (3) (a) Liu, W.; Cao, H.; Zhang, H.; Zhang, H.; Chung, K. H.; He, C.; Wang, H.; Kwong, F. Y.; Lei, A. Organocatalysis in CrossCoupling: DMEDA-Catalyzed Direct C-H Arylation of Unactivated Benzene. J. Am. Chem. Soc. 2010, 132, 16737−16740. (b) Shirakawa, E.; Itoh, K.-i.; Higashino, T.; Hayashi, T. tert-Butoxide-Mediated Arylation of Benzene with Aryl Halides in the Presence of a Catalytic 1,10-Phenanthroline Derivative. J. Am. Chem. Soc. 2010, 132, 15537− 15539. (4) Xu, Z.; Gao, L.; Wang, L.; Gong, M.; Wang, W.; Yuan, R. Visible Light Photoredox Catalyzed Biaryl Synthesis Using Nitrogen Heterocycles as Promoter. ACS Catal. 2015, 5, 45−50. (5) Budén, M. E.; Guastavino, J. F.; Rossi, R. A. Room-Temperature Photoinduced Direct C-H-Arylation via Base-Promoted Homolytic Aromatic Substitution. Org. Lett. 2013, 15, 1174−1177. (6) Barluenga, J.; Gonzalez, J. M.; Garcia-Martin, M. A.; Campos, P. J.; Asensio, G. Acid-Mediated Reaction of Bis(pyridine)iodonium(I) Tetrafluoroborate with Aromatic Compounds. A Selective and General Iodination Method. J. Org. Chem. 1993, 58, 2058−2060. (7) (a) Klapars, A.; Buchwald, S. L. Copper-Catalyzed Halogen Exchange in Aryl Halides: An Aromatic Finkelstein Reaction. J. Am. Chem. Soc. 2002, 124, 14844−14845. (b) Casitas, A.; Canta, M.; Solà, M.; Costas, M.; Ribas, X. Nucleophilic Aryl Fluorination and Aryl Halide Exchange Mediated by a CuI/CuIII Catalytic Cycle. J. Am. Chem. Soc. 2011, 133, 19386−19392. (c) Cant, A. A.; Bhalla, R.; Pimlott, S. L.; Sutherland, A. Nickel-catalysed aromatic Finkelstein reaction of aryl and heteroaryl Bromides. Chem. Commun. 2012, 48, 3993−3995. (d) Chen, M.; Ichikawa, S.; Buchwald, S. L. Rapid and Efficient Copper-Catalyzed Finkelstein Reaction of (Hetero)Aromatics under Continuous-Flow Conditions. Angew. Chem., Int. Ed. 2015, 54, 263−266. (8) (a) Kaur, S.; Kumar, M.; Bhalla, V. Supramolecular ensemble of PBI derivative and copper nanoparticles: A light harvesting antenna for photocatalytic C(sp2)-H functionalization. Green Chem. 2016, 18, 5870−5883. (b) Kaur, M.; Pramanik, S.; Kumar, M.; Bhalla, V. Polythiophene-Encapsulated Bimetallic Au-Fe3O4 Nano-Hybrid Materials: A Potential Tandem Photocatalytic System for Nondirected C(sp2)−H Activation for the Synthesis of Quinoline Carboxylates. ACS Catal. 2017, 7, 2007−2021. (c) Walia, P. K.; Kumar, M.; Bhalla, V. Tailoring of Hetero−oligophenylene Stabilized Nanohybrid Materials: Potential Tandem Photo-Promoted Systems for C−C and C−X Bond Formation Reactions via C-H Activation. ChemistrySelect 2017, 2, 3758−3768. (9) (a) Takagi, K.; Hayama, N.; Inokawa, S. The in Situ-generated Nickel(0)-catalyzed Reaction of Aryl halides with Potassium Iodide and Zinc Powder. Bull. Chem. Soc. Jpn. 1980, 53, 3691−3695. (b) Yang, S. H.; Li, C. S.; Cheng, C. H. Halide Exchange Reactions between Aryl Halides and Alkali Halides Catalyzed by Nickel Metal. J. Org. Chem. 1987, 52, 691−694. (c) Sheppard, T. D. Metal-catalysed halogen exchange reactions of aryl halides. Org. Biomol. Chem. 2009, 7, 1043−1052. (10) (a) Li, L.; Liu, W.; Mu, X.; Mi, Z.; Li, C.-J.. Photo-induced iodination of aryl halides under very mild conditions, 2016, 11, 1948− 1954.10.1038/nprot.2016.125 (b) Li, L.; Liu, W.; Zeng, H.; Mu, X.; Cosa, G.; Mi, Z.; Li, C.-J. Photo-induced Metal-Catalyst-Free Aromatic Finkelstein Reaction. J. Am. Chem. Soc. 2015, 137, 8328−8331. (11) Song, J.; Lee, I.; Roh, J.; Jang, J. Fabrication of Ag-coated AgBr nanoparticles and their plasmonic photocatalytic applications. RSC Adv. 2014, 4, 4558−4563. (12) Qiu, G.; Li, Y.; Wu, J. Recent developments for the photoinduced Ar−X bond dissociation reaction. Org. Chem. Front. 2016, 3, 1011−1027. (13) Barham, J. P.; Coulthard, G.; Emery, K. J.; Doni, E.; Cumine, F.; Nocera, G.; John, M. P.; Berlouis, L. E. A.; McGuire, T.; Tuttle, T.; Murphy, J. A. KOtBu: A Privileged Reagent for Electron Transfer Reactions? J. Am. Chem. Soc. 2016, 138, 7402−7410. (14) (a) Chinchilla, R.; Nájera, C. The Sonogashira Reaction: A Booming Methodology in Synthetic Organic Chemistry. Chem. Soc.
We believe that initially aryl bromide gets converted to aryl iodide by aromatic Finkelstein reaction in the presence of UV light. The aryl C−I bond then undergoes homolytical cleavage to generate a pair of aryl and iodine radicals. The aryl radical then reacts with phenylacetylene to generate a vinyl radical, which abstracts an iodine atom rapidly either from the aryl iodide or the free iodine atom in the solution. Finally, a base abstracts the proton from vinyl iodide to give the desired coupling product (Scheme S3, Supporting Information).16
3. CONCLUSIONS In summary, we have examined a UV light-induced, transitionmetal-free cascade protocol to couple unactivated arenes with all types of activated/unactivated aryl bromides. As per our information, this is the first report for the cascade synthesis of alkynes via aromatic Finkelstein reaction and Sonogashira− Hagihara coupling reaction. This work not only provides a simple and greener protocol for the synthesis of biaryl/alkyne compounds but also contributes toward making the aryl iodide chemistry more green.
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ASSOCIATED CONTENT
* Supporting Information S
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.7b02014. 1 H NMR of compounds 2a−g, 5a−r, and 9a−h; electrospray ionization mass spectrometry of compounds 2a and 2e; tables of control experiments and mechanisms (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected] (V.B.). ORCID
Manoj Kumar: 0000-0002-8740-1928 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS V.B. is thankful to the Science and Engineering Research Board (SERB), New Delhi (ref no. EMR/2014/000149) for financial support. We are also thankful to UGC (New Delhi, India) for the “University with Potential for Excellence” (UPE) project. P.K.W. is thankful to UGC for Senior Research Fellowship (SRF).
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REFERENCES
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DOI: 10.1021/acsomega.7b02014 ACS Omega 2018, 3, 1983−1990
