Porphyrin N-Pincer Pd(II)-Complexes in Water: A Base-Free and Nature-Inspired Protocol for the Oxidative Self-Coupling of Potassium Aryltrifluoroborates in Open-Air

Metalloporphyrins (and porphyrins) are well known as pigments of life in nature, since representatives of this group include chlorophylls (Mg-porphyrins) and heme (Fe-porphyrins). Hence, the construction of chemistry based on these substances can be based on the imitation of biological systems. Inspired by nature, in this article we present the preparation of five different porphyrin, meso-tetraphenylporphyrin (TPP), meso-tetra(p-anisyl)porphyrin (TpAP), tetrasodium meso-tetra(p-sulfonatophenyl)porphyrin (TSTpSPP), meso-tetra(m-hydroxyphenyl)porphyrin (TmHPP), and meso-tetra(m-carboxyphenyl)porphyrin (TmCPP) as well as their N-pincer Pd(II)-complexes such as Pd(II)-meso-tetraphenylporphyrin (PdTPP), Pd(II)-meso-tetra(p-anisyl)porphyrin (PdTpAP), Pd(II)-tetrasodium meso-tetra(p-sulfonatophenyl)porphyrin (PdTSTpSPP), Pd(II)-meso-tetra(m-hydroxyphenyl)porphyrin (PdTmHPP), and Pd(II)-meso-tetra(m-carboxyphenyl)porphyrin (PdTmCPP). These porphyrin N-pincer Pd(II)-complexes were studied and found to be effective in the base-free self-coupling reactions of potassium aryltrifluoroborates (PATFBs) in water at ambient conditions. The catalysts and the products (symmetrical biaryls) were characterized using their spectral data. The high yields of the biaryls, the bio-mimicking conditions, good substrate feasibility, evading the use of base, easy preparation and handling of catalysts, and the application of aqueous media, all make this protocol very attractive from a sustainability and cost-effective standpoint.


Introduction
Synthetic and natural metalloporphyrins are well-known examples of nitrogen-bridged polycyclic compounds and are largely distributed in nature. Metalloporphyrins display a critical role in numerous biological tasks including oxygen transport, health sustainment, bio-organic transformations, and light-harvesting [1][2][3]. Metalloporphyrins display vital catalytic significance in the basic reactions of life; for example, as heme (a cofactor of hemoglobin) in oxygen transport [1,4] and as chlorophyll (which is able to convert sunlight to energy) in photosynthesis of plants [4,5] ( Scheme 1). Several examples of heme and chlorophylls are displayed in Figure 1. Despite these efficient biochemical, photochemical, as heme (a cofactor of hemoglobin) in oxygen transport [1,4] and as chlorophyll (which is able to convert sunlight to energy) in photosynthesis of plants [4,5] ( Scheme 1). Several examples of heme and chlorophylls are displayed in Figure 1. Despite these efficient biochemical, photochemical, and enzymatic functions, the connectivity and controlled rigidity of metalloporphyrins allow highly ordered arrangements in their crystalline frameworks; for example, metal-organic frameworks (MOFs) encompassing an exciting area of research for over a decade in chemical science and technology disciplines [1,5,6].  Besides the biological-catalytic functions of metalloporphyrins, their aptness to a large number of organic transformations as effective catalysts is well-documented [2,7] and is due to the wide selection of metal-ions that can form complexes with porphyrins [2]. The metalloporphyrins have been reported for their catalytic efficiency in cross-coupling reactions [2,[8][9][10][11][12], epoxidations of alkenes [7,13,14], oxidation of alcohols/thiols/benzylic groups/aldehydes [15][16][17], cycloaddition reactions [18,19], reductions of multiple bonds [20,21], aziridinations of olefins [22,23], and olefin cyclopropanations [24,25]. These metalloporphyrins have also been reported as effective catalysts in large scale organic transformations [7] which is an additional benefit together with their in- as heme (a cofactor of hemoglobin) in oxygen transport [1,4] and as chlorophyll (which is able to convert sunlight to energy) in photosynthesis of plants [4,5] ( Scheme 1). Several examples of heme and chlorophylls are displayed in Figure 1. Despite these efficient biochemical, photochemical, and enzymatic functions, the connectivity and controlled rigidity of metalloporphyrins allow highly ordered arrangements in their crystalline frameworks; for example, metal-organic frameworks (MOFs) encompassing an exciting area of research for over a decade in chemical science and technology disciplines [1,5,6].  Besides the biological-catalytic functions of metalloporphyrins, their aptness to a large number of organic transformations as effective catalysts is well-documented [2,7] and is due to the wide selection of metal-ions that can form complexes with porphyrins [2]. The metalloporphyrins have been reported for their catalytic efficiency in cross-coupling reactions [2,[8][9][10][11][12], epoxidations of alkenes [7,13,14], oxidation of alcohols/thiols/benzylic groups/aldehydes [15][16][17], cycloaddition reactions [18,19], reductions of multiple bonds [20,21], aziridinations of olefins [22,23], and olefin cyclopropanations [24,25]. These metalloporphyrins have also been reported as effective catalysts in large scale organic transformations [7] which is an additional benefit together with their in- Besides the biological-catalytic functions of metalloporphyrins, their aptness to a large number of organic transformations as effective catalysts is well-documented [2,7] and is due to the wide selection of metal-ions that can form complexes with porphyrins [2]. The metalloporphyrins have been reported for their catalytic efficiency in cross-coupling reactions [2,[8][9][10][11][12], epoxidations of alkenes [7,13,14], oxidation of alcohols/thiols/benzylic groups/aldehydes [15][16][17], cycloaddition reactions [18,19], reductions of multiple bonds [20,21], aziridinations of olefins [22,23], and olefin cyclopropanations [24,25]. These metalloporphyrins have also been reported as effective catalysts in large scale organic transformations [7] which is an additional benefit together with their inherent safeness and biomimicking properties [2,12]. Hence, the application of metalloporphyrins as catalysts in further organic reactions is interesting and imitates organic reactions of nature.
The catalysts based on transition-metals such as Pd [26,27,[33][34][35][36][37][38][39]41,43], Au [40,[62][63][64], Cu [42,[65][66][67][68], Rh [69], Ru [70], and Fe [71] have been reported for the self-coupling transformations of arylboron compounds but most of the Au, Cu, Rh, Ru, and Fe-based reactions suffer from drawbacks such as the requirement of an external oxidant, a base, organic solvent, low product yields, formation of by-products, and high temperature [26,27]. The Pd-promoted methods, on the other hand, can be performed at rt using mild reaction conditions in a safer solvent such as water [27]. Hence, we undertook the development of a new Pd-based protocol for the synthesis of biaryl using a self-coupling strategy, and found N-pincer Pd(II)-porphyrin complexes as efficient catalysts for this purpose in water, employing PATFBs as attractive substrates. The present protocol using water as reaction media (which is nature s preferred solvent instead of flammable, volatile, and toxic organic solvents [72]), together with metalloporphyrins as catalysts (which are the catalysts of several significant functions in biology), at ambient conditions in open-air can become a nature mimicking protocol for the synthesis of symmetrical biaryls.
The investigations using other arylboron compounds such as, 4-methoxyphenyboronic acid (2), neopentylglycol, and pinacol esters of 4-methoxyphenylboronic acid (3 and 4) and the diethanolamine derivative of 4-methoxyphenylboronic acid (5) showed 92%, 14%, 17%, and 73% yields of 2a (entries 9-12, Table 1), indicating that potassium 4-methoxyphenyltrifluoroborate (1a) is the best substrate for the current self-coupling process. This may be due to the high water solubility of the aryltrifluoroborates. The applicability of this nature-inspired procedure has also been studied using a variety of aryltrifluoroborates (1a-1u). The PATFBs with electron-releasing functionalities (ERFs) such as -OMe, -Me, -Br, -OH, -SMe, and -t Bu at p-, mand o-positions delivered excellent yields (88-98%) of the self-coupling products, 6a-6f, 6l, 6m and 6p with high turnover number (TON) (1760-1960) and turnover frequency (TOF) (2347-7840) values (entries 1-6,12,13,16, Table 2). Electron withdrawing functionalities (EWFs) containing PATFBs at all the p-, m-, and o-positions were found as the best substrates to give 91-99% of self-coupled products, 6g-6k, 6n, 6o, and 6q with large values of TON as 1820-1980 and TOF as 3680-11880 (entries 7-11,14,15,17, Table 2). Unsubstituted PATFB such as 1r and potassium salts of heteroaryltrifluoroborates, 1s-1u also provided excellent isolated yields of self-coupled products under N-pincer Pd(II)-porphyrin, PdTSTpSPP catalyzed reactions in water with excellent yields (86-96%) of products, 6r and 6s-6u with TON, 1720-1920 and TOF, 1720-7680 (entries 18-21, Table 2). This study revealed that the current PdTSTpSPP catalyzed self-coupling of PATFBs shows a large substrate scope irrespective of position and nature of the functional groups. The structures of all the symmetrical biaryls were confirmed using their 1 H NMR, 13 C NMR and mass (LCMS) spectral data (Section 3.2) and the copies of the 1 H NMR and 13 C NMR spectra has been provided at Supplementary Materials with this article.  The applicability of this nature-inspired procedure has also been studied using a variety of aryltrifluoroborates (1a-1u). The PATFBs with electron-releasing functionalities (ERFs) such as -OMe, -Me, -Br, -OH, -SMe, andt Bu at p-, m-and o-positions delivered excellent yields (88-98%) of the self-coupling products, 6a-6f, 6l, 6m and 6p with high turnover number (TON) (1760-1960) and turnover frequency (TOF) (2347-7840) values (entries 1-6,12,13,16, Table 2). Electron withdrawing functionalities (EWFs) containing PATFBs at all the p-, m-, and o-positions were found as the best substrates to give 91-99% of self-coupled products, 6g-6k, 6n, 6o, and 6q with large values of TON as 1820-1980 and TOF as 3680-11880 (entries 7-11,14,15,17, Table 2). Unsubstituted PATFB such as 1r and potassium salts of heteroaryltrifluoroborates, 1s-1u also provided excellent isolated yields of self-coupled products under N-pincer Pd(II)-porphyrin, PdTSTpSPP catalyzed reactions in water with excellent yields (86-96%) of products, 6r and 6s-6u with TON, 1720-1920 and TOF, 1720-7680 (entries 18-21, Table 2). This study revealed that the current PdTSTpSPP catalyzed self-coupling of PATFBs shows a large substrate scope irrespective of position and nature of the functional groups. The structures of all the symmetrical biaryls were confirmed using their 1 H NMR, 13 C NMR and mass (LCMS) spectral data (Section 3.2) and the copies of the 1 H NMR and 13 C NMR spectra has been provided at Supplementary Materials with this article. We also studied the hetero-coupling reaction of PATFBs, 1a and 1r (each with 0.5 mmol) under the present conditions, and observed the formation of self-coupling products 6a and 6r along with the hetero-coupling product 7, in 19%, 21%, and 57% yields in 15 min (Scheme 2). This study indicated that the developed method shows some selectivity in the formation of hetero-coupling products over self-couplings, and hence a detailed investigation may be undertaken towards a complete understanding of the hetero-couplings of arylboron compounds using metalloporphyrin-based catalysts.
The plausible mechanistic futures of PdTSTpSPP catalyzed self-coupling of PATFBs is sketched in Scheme 3 based on previous reports [10][11][12]27,39,73]. The reduction-dissociation process of PdTSTpSPP delivers the Pd(0)-porphyrin intermediate A [10][11][12]. The Pd(0)porphyrin species A is involved in oxidative addition with PATFB 1 and atmospheric oxygen to give Pd(II)-species B, which is on transmetallation with 1 gives the diarylPd(II) intermediate C [27,39,73]. Intermediate C forms symmetrical biaryl 6 and Pd(0)-porphyrin active catalytic principal A on reductive elimination.      We also studied the hetero-coupling reaction of PATFBs, 1a and 1r (each with 0.5 mmol) under the present conditions, and observed the formation of self-coupling products 6a and 6r along with the hetero-coupling product 7, in 19%, 21%, and 57% yields in 15 min (Scheme 2). This study indicated that the developed method shows some selectivity in the formation of hetero-coupling products over self-couplings, and hence a detailed investigation may be undertaken towards a complete understanding of the hetero-couplings of arylboron compounds using metalloporphyrin-based catalysts. The plausible mechanistic futures of PdTSTpSPP catalyzed self-coupling of PATFBs is sketched in Scheme 3 based on previous reports [10][11][12]27,39,73]. The reduction-dissociation process of PdTSTpSPP delivers the Pd(0)-porphyrin intermediate A [10][11][12]. The Pd(0)-porphyrin species A is involved in oxidative addition with PATFB 1 and atmospheric oxygen to give Pd(II)-species B, which is on transmetallation with 1 gives the diarylPd(II) intermediate C [27,39,73]. Intermediate C forms symmetrical biaryl 6 and Pd(0)-porphyrin active catalytic principal A on reductive elimination. We also studied the hetero-coupling reaction of PATFBs, 1a and 1r (each with 0.5 mmol) under the present conditions, and observed the formation of self-coupling products 6a and 6r along with the hetero-coupling product 7, in 19%, 21%, and 57% yields in 15 min (Scheme 2). This study indicated that the developed method shows some selectivity in the formation of hetero-coupling products over self-couplings, and hence a detailed investigation may be undertaken towards a complete understanding of the hetero-couplings of arylboron compounds using metalloporphyrin-based catalysts. The plausible mechanistic futures of PdTSTpSPP catalyzed self-coupling of PATFBs is sketched in Scheme 3 based on previous reports [10][11][12]27,39,73]. The reduction-dissociation process of PdTSTpSPP delivers the Pd(0)-porphyrin intermediate A [10][11][12]. The Pd(0)-porphyrin species A is involved in oxidative addition with PATFB 1 and atmospheric oxygen to give Pd(II)-species B, which is on transmetallation with 1 gives the diarylPd(II) intermediate C [27,39,73]. Intermediate C forms symmetrical biaryl 6 and Pd(0)-porphyrin active catalytic principal A on reductive elimination. We also studied the hetero-coupling reaction of PATFBs, 1a and 1r (each with 0.5 mmol) under the present conditions, and observed the formation of self-coupling products 6a and 6r along with the hetero-coupling product 7, in 19%, 21%, and 57% yields in 15 min (Scheme 2). This study indicated that the developed method shows some selectivity in the formation of hetero-coupling products over self-couplings, and hence a detailed investigation may be undertaken towards a complete understanding of the hetero-couplings of arylboron compounds using metalloporphyrin-based catalysts. The plausible mechanistic futures of PdTSTpSPP catalyzed self-coupling of PATFBs is sketched in Scheme 3 based on previous reports [10][11][12]27,39,73]. The reduction-dissociation process of PdTSTpSPP delivers the Pd(0)-porphyrin intermediate A [10][11][12]. The Pd(0)-porphyrin species A is involved in oxidative addition with PATFB 1 and atmospheric oxygen to give Pd(II)-species B, which is on transmetallation with 1 gives the diarylPd(II) intermediate C [27,39,73]. Intermediate C forms symmetrical biaryl 6 and Pd(0)-porphyrin active catalytic principal A on reductive elimination. We also studied the hetero-coupling reaction of PATFBs, 1a and 1r (each with 0.5 mmol) under the present conditions, and observed the formation of self-coupling products 6a and 6r along with the hetero-coupling product 7, in 19%, 21%, and 57% yields in 15 min (Scheme 2). This study indicated that the developed method shows some selectivity in the formation of hetero-coupling products over self-couplings, and hence a detailed investigation may be undertaken towards a complete understanding of the hetero-couplings of arylboron compounds using metalloporphyrin-based catalysts. The plausible mechanistic futures of PdTSTpSPP catalyzed self-coupling of PATFBs is sketched in Scheme 3 based on previous reports [10][11][12]27,39,73]. The reduction-dissociation process of PdTSTpSPP delivers the Pd(0)-porphyrin intermediate A [10][11][12]. The Pd(0)-porphyrin species A is involved in oxidative addition with PATFB 1 and atmospheric oxygen to give Pd(II)-species B, which is on transmetallation with 1 gives the diarylPd(II) intermediate C [27,39,73]. Intermediate C forms symmetrical biaryl 6 and Pd(0)-porphyrin active catalytic principal A on reductive elimination.

General
The chemical substances utilized in the present homocoupling of PABs were purchased from Spectrochem (Mumbai, India), Alfa Aesar (Haverhill, MA, USA), Merck (Burlington, MA, USA), AVRA (Hyderabad, India), Sigma-Aldrich (St. Louis, MO, USA), and TCI (Tokyo, Japan). Porphyrins and Pd(II)-porphyrin complexes were made from literature reports [2,10,79]. Pyrrole was directly purified by distillation before its use. Silica gel coated thin layer chromatography (TLC) (Merck, Burlington, MA, USA, silica gel-60 F 254 ) was employed to confirm the progress of the self-couplings. Silica gel-packed glass-columns were employed to produce the pure symmetrical biaryls using an eluent of a mixture of EtOAc and hexanes. The Bruker Avance 400/100 MHz NMR spectrometer (Billerica, MA, USA) was employed to record the 1 H and 13 C-NMR spectra and molecular mass was recorded with a Thermo LCQ Max LCMS (Dreieich, Germany).

Synthesis of Porphyrins
TPP: Propanoic acid (180 mL) at 140 • C was added to 75 mL of pyrrole and 8.37 g of benzaldehyde, and the mixture was heated for 1h at 140 • C. The reaction contents were cooled to rt then 110 mL of EtOH was added and stirred at rt for 1 h. The reaction mixture was filtered and the filtrate evaporated in vacuo. Finally, the residue obtained was used to purify the TPP using neutral alumina-packed-column chromatography (CC) with eluent CHCl 3 .
TpAP, TmHPP, and TmCPP: Propionic acid (180 mL) was added to 7.30 g of its anhydride and heated for 5 min at 140 • C. Then, 5.00 g of pyrrole (distilled), and 80 mmol of p-anisaldehyde/m-hydroxybenzaldehyde/m-formylbenzoic acid were added, stirred at 140 • C for 1 h and the mixture cooled to rt. Then 100 mL of EtOH was added, stirred at rt for 1 h, and filtered. The obtained residue was dried in vacuo and subjected to neutral alumina-packed-CC with eluent CHCl 3 to obtain the pure porphyrins, TpAP, TmHPP, and TmCPP.
TSTpSPP: TPP (5 gr) in conc. H 2 SO 4 (60 mL) was heated at 60 • C 16 h and cooled to rt with 12 mL of added ice-cold water. The obtained green colored solution was adjusted to pH between 9-10 using an aqueous solution of saturated NaHCO 3 . The mixture was evaporated in vacuo and thoroughly washed using 2 × 25 mL of CH 2 Cl 2 . A solid precipitate obtained on the addition of 20 mL of MeOH:acetone (3:7) was separated, dried in vacuo, and the TSTpSPP was subjected to purification using neutral Al 2 O 3 -packed-CC with the eluent, MeOH:acetone (3:7).
PdTSTpSPP [10]: TSTpSPP (2.56 g, 2.5 mmol), PdCl 2 (0.53 g, 3 mmol) in 12 mL DMF was refluxed for 2 h and cooled to rt and subjected to evaporation to obtain a dried reaction mass. The crude solid was employed for the purification of PdTSTpSPP using CC with the eluent acetone:MeOH (8:2).

PABs Homocoupling Procedure
To PdTSTpSPP (0.05 mol%) and PATFB (1) (1.10 mmol), 4 mL of deionized water was added and the mixture stirred at rt in open-air for the appropriate time (Table 2). To ensure the completion of the reaction by TLC, to the reaction mixture was added 5 mL water and it was extracted using EtOAc (2 × 5 mL). The EtOAc combined solution was dried in vacuo and subjected to silica-gel packed-CC to obtain the pure symmetrical biaryls (6). The products (6) structures were determined by their 1 H and 13 C NMR and mass data. The characterization data of 6 (Section 3.2) was found to be similar to that of that reported [27,30,66,67] and the copies of 1 H and 13 C NMR spectra has been provided as Supplementary Materials with the manuscript.

Conclusions
To summarize, we developed a new, nature-inspired procedure for the aerobic selfcoupling of PATFBs in water using the nitrogen-bridged polycyclic N-pincer Pd(II)-porphyrin complex, PdTSTpSPP, as a safe catalyst at rt in open-air. This protocol showed advantages with the use of water as solvent, high TON and TOF values, low catalyst loading, large substrate feasibility, and avoidance of oxidant, base, phosphine ligands, and toxic solvents. To the best of our knowledge this is the first report on the use of metalloporphyrins for self-couplings of arylboron compounds.