Development of ligands for metals and metal-catalyzed reactions

Abstract

Provided herein are ligands for transition metals. The ligands are represented by (I). Also provided herein are ligated transition metal complexes that provide a new and / or improved catalytic platform for various carbon-carbon and carbon-heteroatom bond forming reactions. Also provided herein is a method for transition-metal-catalyzed cross-electrophile coupling using these ligands.

Description

[0001] DEVELOPMENT OF LIGANDS FOR METALS AND METAL- CATALYZED REACTIONS Field of Invention The present invention relates to the field of transition metal-based catalyst systems for various carbon-carbon and carbon-heteroatom bond forming reactions, specifically cross-Ullmann coupling reactions. Particularly, the present invention relates to the ligands as a part of the catalyst system in cross-Ullmann coupling reactions. Background and Prior art Transition metal complexes have become useful catalytic tools both in academic laboratories and in industrial plants owing to their diverse reactivity in enabling various carbon-carbon (C-C) and carbon-heteroatom (C-X) bond forming transformations. The catalytic abilities of the complexes are influenced by both the inherent characteristics of the metal and also the presence of supporting ligands around the metal centre. These ligands can significantly enhance the catalytic activity by tuning the reactivity and stability of the metal complexes in the primary coordination sphere. As a consequence, the development of new ligands remains an utmost importance, enabling the discovery of more efficient synthetic transformations with much lower catalyst loadings and mild conditions. Transition metal-catalyzed modern cross-coupling methods for carbon-carbon bond formation has revolutionized the academic and pharmaceutical synthesis through pairing of aryl electrophiles with aryl nucleophiles. The employed aryl nucleophiles are arylboronic acid, arylzinc, aryl magnesium, aryltin, and arylsilicon derivatives, whereas the electrophiles are usually aryl halides or pseudohalides. Over the years the development of numerous catalyst systems paved the way for becoming them a widely applicable method in API production and in the large-scale synthesis of value-added materials. With the successive growth of cross-coupling reactions it suffers from several limiting factors, such as (a) limited commercial availability of nucleophilic carbon reagents, (b) instability of some classes of organoboron reagents, (c) highly reactive nature of many organometallic reagents needs special care to exclude water and dioxygen, (d) the inherent reactivity of organometallic reagents such as RMgX and RZnX or additives required for facilitating the transmetalation step impose restrictions on the use of substrates containing electrophilic functional groups or acidic protons, (e) often requires high temperature and harsh reaction conditions (Everson, D. A.; Weix, D. J. Cross-electrophile coupling: principles of reactivity and selectivity. J. Org. Chem. 2014, 79, 4793; Cox, P. A.; Leach, A. G.; Campbell, A. D.; Lloyd- Jones, G. C. Protodeboronation of Heteroaromatic, Vinyl, and Cyclopropyl Boronic Acids: pH–Rate Profiles, Autocatalysis, and Disproportionation. J. Am. Chem. Soc. 2016, 138, 9145–9157). In recent years, cross-electrophile coupling between two aryl electrophiles, which are stable and more abundant, has been described using multi-transition metal catalyst systems (Ackerman, L. K. G.; Lovell, M. M.; Weix, D. J. Multimetallic catalysed cross- coupling of aryl bromides with aryl triflates. Nature 2015, 524, 454-457. Kang, K.; Loud, N. L.; DiBenedetto, T. A.; Weix, D. J. A General, Multimetallic CrossUllmann Biheteroaryl Synthesis from Heteroaryl Halides and Heteroaryl Triflates. J. Am. Chem. Soc.2021, 143, 21484–21491). Despite significant progress in this field, notable limitations still remain including the coupling of two heteroaromatic (pseudo)halides, use of precious multi- transition metal, the generation of large toxic metallic waste, for which the development of an alternative catalytic system is highly desirable. As it has been well demonstrated that the presence of different substitution in biarylmonophosphine ligands have profound effects on the reaction kinetics in many catalytic reactions. Consequently, there still remains a need for the development of more efficient ligands and catalytic systems for a variety of coupling reactions. Object of Invention It is an object of the present invention to overcome the drawbacks of the prior art. It is an object of the present invention to provide efficient ligands for transition metals to catalyse reactions. It is another object of the present invention to provide transition metal ligands for cross-electrophile coupling reactions. It is a further object of the present invention to provide catalysts systems comprising the transition metal ligands for the coupling reactions. It is also an object of the present invention to provide a process for synthesis of transition metal ligands and the catalyst systems. It is yet another object of the present invention to provide cross-electrophile coupling reactions using the transition metal ligands. Summary of the present invention The following disclosure presents a simplified summary of the invention in order to provide a basic understanding of some aspects of the invention. This summary is not an extensive overview of the present invention. It is not intended to identify the key / critical elements of the invention or to delineate the scope of the invention. Its sole purpose is to present some concept of the invention in a simplified form as a prelude to a more detailed description of the invention presented later. In an aspect there is provided a ligand represented by I:

[0002] Wherein R can be selected independently from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and –(CH2)m-R10; R1, R2, R3, and R4can be selected independently from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and -OR11; or any two adjacent instances of R1, R2, R3and R4can form a five- or six-membered substituted or unsubstituted aryl or heteroaryl ring; R5, R6and R8can be selected independently from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, -OH, -OR12, -NH2, -NHR13, and -N(R14)2; R5and R6can form a five- or six-membered substituted or unsubstituted aryl or heteroaryl ring; R7and R9are selected independently from the group of -N(R14)2; R10, R11, R12, R13, and R14are selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, and heteroaralkyl; m can be an integer in the range 0 to 8. In another aspect there is provided a ligand selected from the group consisting of: In a further aspect there is provided a process for preparing the ligands, the process comprising the steps: a. reacting bromo-2,4-dinitrobenzene and (2-bromophenyl)boronic acid in presence of NaHCO3and Pd(PPh3)4in a solvent mixture of DME and H2O (2:1) at 110 °C for 8 h to obtain 2'-bromo-2,4-dinitro-1,1'-biphenyl; b. reacting 2'-bromo-2,4-dinitro-1,1'-biphenyl with NH4Cl in presence of Fe powder iniPrOH and H2O for 2h and cooled to room temperature to obtain 2'-bromo-[1,1'-biphenyl]-2,4-diamine; c. reacting 2'-bromo-[1,1'-biphenyl]-2,4-diamine with MeI in presence of sodium hydride in THF at room temperature for 9h to obtain 2'-bromo- N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine; d. mixing 2'-bromo-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine with THF and n-BuLi for 40 min at -78 °C; and e. adding a regent selected from Cy2PCl,iPr2PCl or Ph2PCl to the reaction mixture of step (d) at -78 °C to obtain the ligand. In yet another aspect there is provided a phosphino palladacyclic complex as precatalyst selected from the group consisting of:

[0003] In another aspect there is provided a method of cross-Ullmann coupling represented by the following reaction: Wherein P can be selected from the group consisting of substituted or unsubstituted aryl and heteroaryl; Z can be selected from the group consisting of substituted or unsubstituted aryl and heteroaryl; Q can be selected from the group consisting of -I, -Br, -Cl, -OSO2R'; Y can be selected from the group consisting of -I, -Br, -Cl, -OSO2R'; R' is selected from the group consisting of alkyl, perfluoroalkyl, aryl, and heteroaryl; transition metal can be selected from the group consisting of Ni and Pd; the ligand is selected from the group consisting of the ligands according to the present invention; the base can be selected from the group consisting of hydrides, fluorides, hydroxides, carbonates, phosphates, alkoxides, metal amides, and carbanions; solvent can be selected from the group consisting of acetonitrile, toluene, acetone, and THF. Other aspects, advantages, and salient features of the invention will become apparent to those skilled in the art from the following detailed description. Brief Description of Accompanying Drawings Figure 1 illustrates the X-ray structure of ligand 3 Figure 2 illustrates the X-ray structure of precatalyst 11 Detailed description of the present invention The present invention relates to the development of novel ligands for transition metals. The following description is provided to assist in a comprehensive understanding of various embodiments of the present disclosure as defined by the claims and their equivalents. It includes various specific details to assist in that understanding, but these are to be regarded as merely exemplary. Accordingly, those of ordinary skill in the art will recognize that various changes and modifications of the various embodiments described herein can be made without departing from the scope and spirit of the present disclosure. In addition, descriptions of well-known functions and constructions may be omitted for clarity and conciseness. The terms and words used in the following description and claims are not limited to the bibliographical meanings, but, are merely used by the inventor to enable a clear and consistent understanding of the present disclosure. Accordingly, it should be apparent to those skilled in the art that the following description of various embodiments of the present disclosure is provided for illustration purpose only and not for the purpose of limiting the present disclosure as defined by the appended claims and their equivalents. All terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which various embodiments belong. Further, the meaning of terms or words used in the specification and the claims should not be limited to the literal or commonly employed sense but should be construed in accordance with the spirit of the disclosure to most properly describe the present disclosure. The terminology used herein is for the purpose of describing particular various embodiments only and is not intended to be limiting of various embodiments. As used herein, the singular forms "a," "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising" used herein specify the presence of stated features, integers, steps, operations, members, components, and / or groups thereof, but do not preclude the presence or addition of one or more other features, integers, steps, operations, members, components, and / or groups thereof. The term “heteroatom” is art-recognized and refers to an atom of any element other than carbon or hydrogen, for example, boron, nitrogen, oxygen, phosphorus, sulfur and selenium. The term “alkyl” is art-recognized, and includes saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups. The term “aryl” is prior art-recognized and refers to 6-membered unsubstituted or substituted single-ring aromatic groups, for example, benzene, naphthalene, anthracene, pyrene, and the like. The term “heteroaryl” is prior art-recognized and refers to aryl groups having heteroatoms in the ring structure, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine, and the like. The term “aralkyl” is art-recognized and refers to an alkyl group substituted with an aryl group. The term “heteroaralkyl” is prior art-recognized and refers to an alkyl groups substituted with an heteroaryl group. The present invention discloses ligands for transition metals. These ligated transition metal complexes can be used as catalysts in various carbon-carbon and carbon-heteroatom bond forming reactions. For example, ligands of the present invention portray unprecedented reactivity in the developed palladium catalyzed cross-electrophile coupling reactions. An aspect of the present invention relates to the synthesis of these ligand containing palladacyclic complex, which could be used as a precatalyst in various carbon-carbon and carbon-heteroatom bond forming reactions with remarkable improvements in many features of the catalytic reactions. The ligand as provided in the present invention is represented by I: Wherein R can be selected independently from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and –(CH2)m-R10; R1, R2, R3, and R4can be selected independently from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and -OR11; or any two adjacent instances of R1, R2, R3and R4can form a five- or six-membered substituted or unsubstituted aryl or heteroaryl ring; R5, R6and R8can be selected independently from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, -OH, -OR12, -NH2, -NHR13, and -N(R14)2; R5and R6can form a five- or six-membered substituted or unsubstituted aryl or heteroaryl ring; R7and R9are selected independently from the group of -N(R14)2; R10, R11, R12, R13, and R14are selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, and heteroaralkyl; m can be an integer in the range 0 to 8. In an embodiment, R is iso-propyl (i-Pr). In another embodiment, R is cyclohexyl (Cy). In a further embodiment, R is phenyl (Ph). In one embodiment, R1, R2, R3, and R4are hydrogen and R5, R6, and R8are hydrogen. In one embodiment, R7and R9are NMe2. In a preferred embodiment, R is cyclohexyl (Cy), R1, R2, R3, R4, R5, R6, and R8are hydrogen and R7and R9are NMe2. In another preferred embodiment, R is iso-propyl (i-Pr), R1, R2, R3, R4, R5, R6, and R8are hydrogen and R7and R9are NMe2. In yet another preferred embodiment, R is phenyl (Ph), R1, R2, R3, R4, R5, R6, and R8are hydrogen and R7and R9are NMe2. The present invention provides a ligand selected from the group consisting of: The present inventors have developed a new approach of cross-Ullmann coupling i.e., the coupling between two different (hetero)aryl halides using these ligands with specific transition metals. The other ligands of the prior art were not effective for this transformation. The ligands of the present invention promote, for the first time, the highly selective cross-Ullmann coupling of (hetero)aryl halides using only single palladium catalyst. Besides, these ligands can also be utilized for traditional cross-coupling reactions of prior art. as shown in three examples in scheme 9 and 10. The present invention also relates to the process for preparation of the ligands. The process for preparing the ligands includes the steps of: Step 1. Synthesis of 2'-bromo-2,4-dinitro-1,1'-biphenyl 1-bromo-2,4-dinitrobenzene is reacted with (2-bromophenyl)boronic acid and in presence of Pd(PPh3)4 Step 2. Synthesis of 2'-bromo-[1,1'-biphenyl]-2,4-diamine 2'-bromo-2,4-dinitro-1,1'-biphenyl of step 1, Fe-powder, and NH4Cl were reacted. Then iPrOH and H2O was added Step 3. Synthesis of 2'-bromo-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4- diamine To 2'-bromo-[1,1'-biphenyl]-2,4-diamine of step 2, THF and sodium hydride was added. MeI was added to the above solution. The steps 1, 2, and 3 along with the reaction conditions are illustrated in Scheme 1 below. Scheme 1 The 2'-bromo-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine formed in Step 3 is reacted further downstream to form the ligands. Synthesis of ligands 1 and 2 2'-bromo-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine and THF was added to form a reaction mixture. n-BuLi was added followed by addition of Cy2PCl oriPr2PCl. The step and reaction conditions for preparing ligands 1 and 2 are illustrated in Synthesis of ligand 3 2'-bromo-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine and THF was added to form a reaction mixture. n-BuLi was added followed by addition of Ph2PCl. The step and reaction conditions for preparing ligand 3 are illustrated in Scheme 3.

[0004] Scheme 3 Therefore, in an embodiment there is provided a process for preparing the ligands, the process comprising the steps: a. reacting bromo-2,4-dinitrobenzene and (2-bromophenyl)boronic acid in presence of NaHCO3 and Pd(PPh3)4 in a solvent mixture of DME and H2O (2:1) at 110 °C for 8 h to obtain 2'-bromo-2,4-dinitro-1,1'-biphenyl; b. reacting 2'-bromo-2,4-dinitro-1,1'-biphenyl with NH4Cl in presence of Fe powder iniPrOH and H2O for 2 h and cooled to room temperature to obtain 2'-bromo-[1,1'-biphenyl]-2,4-diamine; c. reacting 2'-bromo-[1,1'-biphenyl]-2,4-diamine with MeI in presence of sodium hydride in THF at room temperature for 9h to obtain 2'-bromo- N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine; d. mixing 2'-bromo-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine with THF and n-BuLi for 40 min at -78 °C; e. adding a regent selected from Cy2PCl,iPr2PCl or Ph2PCl to the reaction mixture of step (d) at -78 °C to obtain the ligand. The present invention also provides ligand containing palladacyclic complex. Such complex is used as precatalysts. Precatalysts of the present invention are stable ligated Palladium(II) complexes which can be activated under the reaction conditions to generate monoligated Pd(0) active species, thus allowing the reaction to proceed efficiently with increased catalytic activity even at low catalyst loadings. Considering their ability to form active catalyst in-situ it is expected to modulate the catalytic paradigm of various other bond forming reactions. The phosphino palladacyclic complex as precatalyst is selected from the group consisting of: The present invention also provides a process for the synthesis of the phosphino palladacyclic complex or the precatalysts as described herein. In one embodiment, there is provided a process for preparing a Pd-Precatalysts 5. The process involves synthesis of [PhCH2CH2NH3]OTf and triflate bridge palladacyclic dimer represented as 4. The dimeric Pd-complex 4 and ligand L1 was mixed in presence of DCM to get corresponding phosphino palladacyclic complex 5. In one embodiment, there is provided a process for preparing a Pd-Precatalysts 6. The process involves synthesis of [PhCH2CH2NH3]OTf and triflate bridge palladacyclic dimer represented as 4. The dimeric Pd-complex 4 and ligand L3 was mixed in presence of DCM to get corresponding phosphino palladacyclic complex 6. The preparation of phosphino palladacyclic complex 5 and 6 is illustrated in Scheme 4 as below along with the process parameters. Scheme 4 there is provided a process for preparing a Pd-Precatalysts 8. synthesis of 2-ammoniumbiphenyl chloride and chloride bridge palladacyclic dimer 7. The chloride bridge dimeric complex 7 and ligand L1 was mixed in presence of THF to get corresponding phosphino palladacyclic complex 8. In one embodiment, there is provided a process for preparing a Pd-Precatalysts 9. The process involves synthesis of 2-ammoniumbiphenyl chloride and chloride bridge palladacyclic dimer 7. The chloride bridge dimeric complex 7 and ligand L3 was mixed in presence of THF to get corresponding phosphino palladacyclic complex 9. The preparation of phosphino palladacyclic complex 8 and 9 is illustrated in Scheme 5 as below along with the process parameters. Scheme 5 In one embodiment, there is provided a process for preparing a Pd-Precatalysts 11. The process involves synthesis of 2-ammoniumbiphenyl mesylate and mesylate bridge palladacyclic dimer 10. The mesylate bridge palladacyclic dimer 10 and ligand L1 was mixed in presence of THF to get corresponding phosphino palladacyclic complex 11. In one embodiment, there is provided a process for preparing a Pd-Precatalysts 12. The process involves synthesis of 2-ammoniumbiphenyl mesylate and mesylate bridge palladacyclic dimer 10. The mesylate bridge palladacyclic dimer 10 and ligand L3 was mixed in presence of THF to get corresponding phosphino palladacyclic complex 12. The preparation of phosphino palladacyclic complex 11 and 12 is illustrated in Scheme 6 as below along with the process parameters.

[0005] Scheme 6 In one embodiment, there is provided a process for preparing a Pd-Precatalysts 14. The process involves synthesis of N-Methyl-2-aminobiphenyl and sulfonate bridge palladacyclic dimer 13. The sulfonate bridge palladacyclic dimer 13 and ligand L1 was mixed in presence of DCM to get corresponding phosphino palladacyclic complex 14. In one embodiment, there is provided a process for preparing a Pd-Precatalysts 15. The process involves synthesis of N-Methyl-2-aminobiphenyl and sulfonate bridge palladacyclic dimer 13. The sulfonate bridge palladacyclic dimer 13 and ligand L3 was mixed in presence of DCM to get corresponding phosphino palladacyclic complex 15. The preparation of phosphino palladacyclic complex 14 and 15 is illustrated in Scheme 7 as below along with the process parameters. Scheme 7 Cross-electrophile coupling is a type of reaction where both the coupling partner would be carbon electrophile, it can be either alkyl or (hetero)aryl halides and pseudohalides. When both the carbon electrophile will be from (hetero)aryl halides or pseudohalides it is termed as cross-Ullmann coupling. There are several approaches of cross-Ulmann coupling reported in the literature over the decades, but all these approaches require forcing conditions and multiple metals for desired product formation. Herein, the inventors have introduced a completely new approach of successfully achieving cross-Ullmann coupling using only a single metal with the ligands described herein. The ligands described herein act as a supporting ligand for metal to form a metal-supporting ligand complex into the reaction solution, modulating the elementary steps of the protocol to enable successful cross-Ullmann coupling reaction. Accordingly, the present invention also relates to a method of cross-Ullmann coupling coupling represented by the following reaction: Wherein P can be selected from the group consisting of substituted or unsubstituted aryl and heteroaryl; Z can be selected from the group consisting of substituted or unsubstituted aryl and heteroaryl; Q can be selected from the group consisting of -I, -Br, -Cl, -OSO2R'; Y can be selected from the group consisting of -I, -Br, -Cl, -OSO2R'; R' is selected from the group consisting of alkyl, perfluoroalkyl, aryl, and heteroaryl; transition metal can be selected from the group consisting of Ni and Pd; the ligand can be selected from the group consisting of the ligands as described herein; the base can be selected from the group consisting of hydrides, fluorides, hydroxides, carbonates, phosphates, alkoxides, metal amides, and carbanions; solvent can be selected from the group consisting of acetonitrile, toluene, acetone, and THF. As described in the method above, the period of time is from 12 h to 24 h, the temperature is about 35 °C to 40 °C (room temperature) and the light source is either 440 nm or 456 nm blue LED. In one embodiment, the Cross-Electrophile Coupling Reactions follows General Procedure A (Scheme 8). To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added ligand (10 mol%), Pd(OAc)2 (5 mol%), (hetero)aryl iodide (0.2 mmol, 1.0 equiv. for solid and non-volatile substrates), and (hetero)aryl bromide (0.2 mmol, 1.0 equiv. for solid and non- volatile substrates). The tube was moved into the glovebox where was added the liquid and volatile substrates, and base (3.0 equiv.). The tube was sealed with a Teflon screw cap septum and removed from the glovebox. Anhydrous CH3CN (1.5 mL) was added under argon atmosphere. The reaction was stirred and irradiated with a 440 nm or 456 nm Kessil PR-160L Blue LED lamp (100% LED intensity, 3 cm away, with a cooling fan to keep the reaction temperature at 35- 40 °C and keeping the reaction region located in the center of LEDs lamp) for 24 hours. The reaction mixture was diluted with 2 mL of ethyl acetate and filtered through a pad of celite, eluting with EtOAc. The filtrate was concentrated with the aid of a rotary evaporator. The resulting crude material was then purified by flash chromatography. Scheme 8 The cross-Ullmann coupling can also be used to synthesize representative examples of pharmaceutically relevant (hetero)biaryl moiety using the exemplary ligands of the present invention as shown in Scheme 9 Scheme 9 In another embodiment, the ligands of the present invention can be used in Suzuki-Miyaura cross-coupling reactions following General Procedure B as described in Scheme 10. To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added ligand (2 mol%), Pd(OAc)2 (1 mol%), (hetero)aryl halide (0.2 mmol, 1.0 equiv. for solid and non-volatile substrates), (hetero)aryl boronic acid (0.24 mmol, 1.2 equiv. for solid and non- volatile substrates), and K3PO4 (2.0 equiv.). The tube was sealed, and evacuated and backfilled with argon (this process was repeated a total of 3 times). Then liquid and volatile substrates, and a degassed solvent mixture of THF and H2O (THF:H2O = 3:1, 2 mL) were added via syringe. The tube was submerged in a preheated oil bath where the reaction mixture was stirred vigorously at 60 °C for 10 h. The reaction mixture was then cooled to room temperature, diluted with 2 mL of ethyl acetate, and filtered through a pad of celite, eluting with EtOAc. The filtrate was concentrated with the aid of a rotary evaporator. The resulting crude material was then purified by flash chromatography. Scheme 10 In yet another embodiment, the ligands of the present invention can be used in C- N Cross-Coupling Reactions following General Procedure C as described in Scheme 11. To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added ligand (2 mol%), Pd(OAc)2(1 mol%), (hetero)aryl bromide or (hetero)aryl triflate (0.2 mmol, 1.0 equiv. for solid and non-volatile substrates), amine (0.26 mmol, 1.3 equiv. for solid and non-volatile substrates), and NaOtBu (2.0 equiv.). The tube was sealed, and evacuated and backfilled with argon (this process was repeated a total of 3 times). Then liquid and volatile substrates, and degassed 1,4-dioxane (2 mL) were added via syringe. The tube was submerged in a preheated oil bath where the reaction mixture was stirred vigorously at 110 °C for 12 h. The reaction mixture was then cooled to room temperature, diluted with 2 mL of ethyl acetate, and filtered through a pad of celite, eluting with EtOAc. The filtrate was concentrated with the aid of a rotary evaporator. The resulting crude material was then purified by flash chromatography.

[0006] Scheme 11 The present invention is now being illustrated by way of non-limiting examples. The examples are intended to be purely exemplary of the invention and should therefore not be considered to limit the invention in any way. Efforts have been made to ensure accuracy with respect to numbers used, but some experimental errors and deviations should be accounted for. Examples The following examples are included merely for purposes of better illustration of the present invention, and are not to be interpreted in any way as limiting the scope of the invention. Materials and Methods General Reagent Information Unless otherwise stated, all air and moisture sensitive reactions were carried out under an argon atmosphere using standard Schlenk / Glove box techniques. The 1- bromo-2,4- dinitrobenzene (from Sigma-Aldrich or TCI), (2- bromophenyl)boronic acid (from Zeta scientific), Pd(PPh3)4 (from Zeta Scientific), Pd(OAc)2 (from Sigma Aldrich), Fe-powder (from Sigma-Aldrich) were purchased and used as received without further purification. THF and toluene were purchased from Alfa Aesar or Spectrochem and anhydrous diethyl ether was purchased from Sigma-Aldrich, and was distilled under argon from sodium benzophenone ketyl. CH3CN and DCM were purchased from Loba Chemie, Spectrochem, or Sigma Aldrich, and were dried under argon from CaH2. All other fine chemicals and solvents were purchased from Sigma-Aldrich, Alfa Aesar, Spectrochem, Avra, or Zeta Scientific. Cesium carbonate was purchased from Alfa Aesar, TCI, or Sigma-Aldrich and used as received. The bulk of the bases were stored in a N2glovebox. General Analytical Information All compounds were characterized by1H NMR,13C NMR,31P NMR (when applicable), IR spectroscopy, and high-resolution mass spectrometry (HRMS). Nuclear Magnetic Resonance spectra were recorded on Bruker 500 MHz or Bruker 400 MHz spectrometers. All1H NMR experiments are reported in δ units, parts per million (ppm), and were measured relative to the signals for residual chloroform (7.26 ppm) in the deuterated solvent, unless otherwise stated. All13C NMR spectra are reported in ppm relative to deuterochloroform (77.16 ppm), unless otherwise stated, and all were obtained with1H decoupling. Data for1H are reported as follows: chemical shift ( ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, h = hextet, hept = heptet, m = multiplet, br = broad), coupling constant (Hz), and integration. High resolution mass spectrometry (HRMS-ESI) experiments were performed on Agilent 6530 Accurate-Mass Q-TOF LC / MS in ESI mode. X-ray crystallography was recorded at Department of Chemistry, IIT Bombay. FT-IR were recorded on an Agilent Cary 630 instrument and are reported in wavenumbers (cm–1). Analytical TLC: aluminum backed plates pre-coated (0.25 mm) with Merck Silica Gel 60 F254. Compounds were visualized by exposure to UV-light or by dipping the plates in permanganate (KMnO4) stain followed by heating or by dipping the plates in iodine chamber. Flash column chromatography was performed using Merck Silica Gel (100-200 mesh). All mixed solvent eluents are reported as v / v solutions. Example 1: Synthesis of 2'-bromo-2,4-dinitro-1,1'-biphenyl To an oven-dried Schlenk tube (100 mL) equipped with a magnetic stir bar was added 1-bromo-2,4-dinitrobenzene (4.9 g, 20.0 mmol, 1.0 equiv.), (2- bromophenyl)boronic acid (4.8 g, 24.0 mmol, 1.2 equiv.), and NaHCO3 (5.0 g, 60.0 mmol, 3 equiv.). The tube was moved into the glovebox where Pd(PPh3)4(231.1 mg, 0.2 mmol, 1 mol%) was added. The tube was sealed with a rubber septum and removed from the glovebox. A degassed solvent mixture of DME and H2O (2:1, 30 mL) was added via syringe under continuous flow of argon. The rubber septum was then quickly exchanged for a teflon screw cap. Then the reaction mixture was stirred at 110 °C for 8 h. After being cooled to room temperature, the DME was evaporated by rotary evaporator. The mixture was transferred to a separatory funnel and extracted by EtOAc three times. The combined organic phases were dried over Na2SO4, and filtered. After removal of volatile components from the filtrate, the resulting crude product was purified by flash chromatography (Petroleum ether:EtOAc = 94:6) to give 2'-bromo-2,4- dinitro-1,1'-biphenyl as a yellow solid (5.89 g, 92% yield).1H NMR (400 MHz, CDCl3) δ 8.96 (d, J = 2.3 Hz, 1H), 8.53 (dd, J = 8.4, 2.3 Hz, 1H), 7.69 (dd, J = 8.0, 1.2 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.45 (td, J = 7.5, 1.2 Hz, 1H), 7.35 (td, J = 7.7, 1.7 Hz, 1H), 7.27 – 7.22 (m, 1H).13C NMR (126 MHz, CDCl3) δ 148.61, 147.68, 141.99, 137.25, 134.09, 133.01, 130.69, 129.47, 127.93, 127.23, 121.97, 120.18. Example 2: Synthesis of 2'-bromo-[1,1'-biphenyl]-2,4-diamine To an oven-dried two-neck 100 mL round bottom flask equipped with a magnetic stir bar was added 2'-bromo-2,4-dinitro-1,1'-biphenyl (2.4 g, 7.4 mmol, 1.0 equiv.), Fe-powder (6.6 g, 118.0 mmol, 16.0 equiv.), and NH4Cl (4.2 g, 78 mmol, 10 equiv.). TheniPrOH (25 mL) and H2O (25 mL) was added via syringe. The reaction was heated to reflux and CH3COOH (4.8 mL) was added slowly via syringe. The reaction mixture was allowed to stir at reflux for 2 h and was then cooled to room temperature. After completion of the reaction, the reaction mixture was extracted with ethyl acetate three times. The combined organic phases were dried over Na2SO4, and filtered. The resulting crude product obtained after removal of the solvent with the aid of a rotary evaporator was purified by flash chromatography (Petroleum ether:EtOAc = 50:50) to give 2'-bromo-[1,1'- biphenyl]-2,4-diamine as a brown solid (1.75 g, 90% yield).1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.0 Hz, 1H), 7.38 – 7.30 (m, 2H), 7.22 – 7.17 (m, 1H), 6.83 (d, J = 8.0 Hz, 1H), 6.20 (dd, J = 8.0, 2.1 Hz, 1H), 6.11 (d, J = 2.3 Hz, 1H), 3.55 (br s, 4H).13C NMR (101 MHz, CDCl3) δ 147.42, 144.53, 140.22, 133.07, 132.49, 131.30, 128.92, 127.79, 125.15, 118.51, 105.88, 101.81. HRMS (ESI): Calculated for C12H12BrN2 [M+H+]: 263.0181; found: 263.0181. Example 3: Synthesis of 2'-bromo-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]- 2,4-diamine To an oven dried 25 ml round bottom flask equipped with a magnetic stir bar was added 2'-bromo-[1,1'-biphenyl]-2,4-diamine (500 mg, 1.9 mmol, 1.0 equiv.). THF (10 mL) was added and the reaction was cooled to 0 °C and sodium hydride (60% in mineral oil, 800 mg, 22.8 mmol, 12 equiv.) was added. The solution was stirred for 30 min and then the MeI (2 mL, 32.0 mmol, 17 equiv.) was added via syringe in a dropwise fashion. The reaction mixture was warmed slowly to room temperature where it was stirred for an additional 9 h. After completion the reaction mixture was quenched with ice-cold saturated aqueous solution of NH4Cl. The mixture was transferred to a separatory funnel and extracted by EtOAc three times. The combined organic phases were dried over Na2SO4, and filtered. The resulting crude product obtained after removal of the solvent with the aid of a rotary evaporator was purified by flash chromatography (Petroleum ether:EtOAc = 96:4) to give 2'-bromo-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine as a light yellow solid (454.9 mg, 75% yield).1H NMR (500 MHz, CDCl3) δ 7.68 (d, J = 8.1 Hz, 1H), 7.40 (dd, J = 7.6, 1.8 Hz, 1H), 7.32 (t, J = 7.4 Hz, 1H), 7.17 – 7.10 (m, 1H), 7.05 (d, J = 8.9 Hz, 1H), 6.46 – 6.42 (m, 2H), 3.03 (s, 6H), 2.58 (s, 6H).13C NMR (126 MHz, CDCl3) δ 152.29, 150.98, 142.84, 132.95, 132.63, 132.46, 127.67, 127.10, 124.70, 122.50, 105.24, 102.02, 43.30, 40.64. Example 4: Synthesis of Ligand 1 To an oven-dried two-neck 100 mL round bottom flask equipped with a magnetic stir bar and fitted with a teflon septum was added 2'-bromo-N2,N2,N4,N4- tetramethyl-[1,1'-biphenyl]-2,4-diamine (1.0 g, 3.15 mmol, 1.0 equiv.), and then evacuated and backfilled with argon (this process was repeated a total of 3 times). THF (13 mL) was added via syringe and the reaction mixture was cooled to - 78 °C. n-BuLi (2.5 M in hexanes, 1.3 mL, 3.3 mmol, 1.05 equiv.) was added in a dropwise fashion. The reaction mixture was stirred for 40 min at -78 °C. Then the Cy2PCl (0.8 mL, 3.46 mmol, 1.1 equiv.) was added via syringe in a dropwise fashion. The reaction mixture was allowed to stir for 1 h at -78 °C followed by warmed slowly to room temperature. The reaction was quenched by addition of methanol (2 mL) and filtered through a pad of silica gel topped with a layer of celite, eluting with ethyl acetate. The solvent was evaporated with the aid of a rotary evaporator to give a sticky yellow liquid. The resulting crude material was then purified by flash chromatography (Petroleum ether:EtOAc = 95:5) to give 2'- (dicyclohexylphosphanyl)-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine (1.17 g, 86% yield) as a pale yellow solid.1H NMR (500 MHz, CDCl3) δ 7.59 (t, J = 7.2 Hz, 1H), 7.42 – 7.37 (m,1H), 7.36 – 7.33 (m, 1H), 7.33 – 7.29 (m, 1H), 6.97 (t, J = 7.4 Hz, 1H), 6.45 – 6.38 (m, 2H), 3.04 (d, J = 6.7 Hz, 6H), 2.52 (d, J = 6.7 Hz, 6H), 2.08 (s, 1H), 1.90 – 1.81 (m, 2H), 1.79 – 1.63 (m, 6H), 1.44 – 0.85 (m, 13H).13C NMR (126 MHz, CDCl3) δ 152.10, 152.08, 150.60, 150.17, 149.93, 135.73, 135.58, 133.01, 132.99, 132.74, 132.70, 131.12, 131.07, 128.43, 125.33, 124.73, 124.68, 105.09, 101.93, 43.29, 40.61, 36.79, 36.67, 33.60, 33.48, 30.85, 30.73, 30.64, 30.49, 29.80, 29.70, 28.62, 28.57, 27.81, 27.71, 27.65, 27.61, 27.55, 27.38, 27.29, 26.77, 26.53.31P NMR (202 MHz, CDCl3) δ -10.04. HRMS (ESI): Calculated for C28H42N2P [M+H+]: 437.3090; found: 437.3090. Example 5: Synthesis of Ligand 2 To an oven-dried two-neck 100 mL round bottom flask equipped with a magnetic stir bar and fitted with a teflon septum was added 2'-bromo-N2,N2,N4,N4- tetramethyl-[1,1'-biphenyl]-2,4-diamine (1.0 g, 3.15 mmol, 1.0 equiv.), and then evacuated and backfilled with argon (this process was repeated a total of 3 times). THF (13 mL) was added via syringe and the reaction mixture was cooled to - 78 °C. n-BuLi (2.5 M in hexanes, 1.3 mL, 3.3 mmol, 1.05 equiv.) was added in a dropwise fashion. The reaction mixture was stirred for 40 min at -78 °C. Then the iPr2PCl (0.6 mL, 3.46 mmol, 1.1 equiv.) was added via syringe in a dropwise fashion. The reaction mixture was allowed to stir for 2 h at -78 °C followed by warmed slowly to room temperature. The reaction was quenched by addition of methanol (2 mL) and filtered through a pad of silica gel topped with a layer of celite, eluting with ethyl acetate. The solvent was evaporated with the aid of a rotary evaporator to give a sticky yellow liquid. The resulting crude material was then purified by flash chromatography (Petroleum ether:EtOAc = 95:5) to give 2'- (diisopropylphosphanyl)-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine as a light yellow solid (0.9 g, 82% yield).1H NMR (500 MHz, CDCl3) δ 7.54 (br s, 1H), 7.37 (t, J = 7.5 Hz, 1H), 7.32 – 7.27 (m, 2H), 6.94 (d, J = 8.7 Hz, 1H), 6.42 – 6.36 (m, 2H), 3.00 (s, 6H), 2.47 (s, 6H), 2.24 (br s, 1H), 1.81 (br s, 1H), 1.15 (dd, J = 14.6, 6.6 Hz, 3H), 0.99 (dd, J = 13.0, 6.8 Hz, 3H), 0.87 – 0.80 (m, 6H).31P NMR (202 MHz, CDCl3) δ -1.88. HRMS (ESI): Calculated for C22H33N2PNa [M+Na+]: 379.2276; found: 379.2276. Example 6: Synthesis of Ligand 3 To an oven-dried two-neck 100 mL round bottom flask equipped with a magnetic stir bar and fitted with a teflon septum was added 2'-bromo-N2,N2,N4,N4- tetramethyl-[1,1'-biphenyl]-2,4-diamine (1.0 g, 3.15 mmol, 1.0 equiv.), and then evacuated and backfilled with argon (this process was repeated a total of 3 times). THF (13 mL) was added via syringe and the reaction mixture was cooled to - 78 °C. n-BuLi (1.6 M in hexanes, 2.0 mL, 3.3 mmol, 1.05 equiv.) was added in a dropwise fashion and the resulting mixture was stirred for 40 min at -78 °C. The Ph2PCl (0.7 mL, 3.78mmol, 1.2 equiv.) was added via syringe in a dropwise fashion. The reaction mixture was stirred for 2.5 h at -78 °C and then warmed slowly to room temperature where it was allowed to stir for overnight (12 h). The reaction was quenched by addition of methanol (2 mL) and filtered through a pad of silica gel topped with a layer of celite, eluting with ethyl acetate. The solvent was evaporated with the aid of a rotary evaporator to give a sticky yellow liquid. The resulting crude material was then purified by flash chromatography (Petroleum ether:EtOAc = 95:5) to give the title compound as a white solid (1.15 g, 88%).1H NMR (500 MHz, CDCl3) δ 7.53 – 7.44 (m, 2H), 7.42 – 7.35 (m, 5H), 7.35 – 7.32 (m, 1H), 7.31 – 7.24 (m, 6H), 7.01 (d, J = 8.2 Hz, 1H), 6.48 – 6.40 (m, 2H), 3.06 (s, 6H), 2.33 (s, 6H).13C NMR (126 MHz, CDCl3) δ 152.49, 150.90, 149.11, 148.84, 140.86, 140.74, 139.14, 139.04, 136.43, 136.35, 136.19, 136.17, 133.35, 133.19, 133.09, 132.94, 132.56, 132.54, 130.74, 130.69, 129.21, 128.12, 128.06, 128.01, 127.70, 127.60, 126.28, 124.00, 123.95, 105.63, 101.94, 42.80, 40.58.31P NMR (202 MHz, CDCl3) δ -14.05. Example 7: Synthesis of Pd-Precatalysts 5 and 6 Step 1: Synthesis of [PhCH2CH2NH3]OTf To an oven-dried round bottom flask equipped with a magnetic stir bar was added phenethylamine (0.25 mL, 2.0 mmol, 1.0 equiv.) and diethyl ether (10 mL). Triflic acid (2.21 mL, 4.4 mmol, 1.2 equiv.) was slowly added to this solution and the resulting white suspension was vigorously stirred for 30 min. Then the mixture was filtered and the solid residue was washed with diethyl ether (2 × 5 mL) and dried under vacuum to give compound as white powder (459 mg, 85% yield) [1H and13C matched with reference- Vicente, J.; Saura-Llamas, I.; Oliva- Madrid, M.-J.; García-López, J.-A.; Bautista, D. A New Method for High-Yield Cyclopalladation of Primary and Secondary Amines. Atom-Efficient Open-to-Air Inexpensive Synthesis of Buchwald-Type Precatalysts. Organometallics 2011, 30, 17, 4624–4631]. Step 2: Synthesis of triflate bridge palladacyclic dimer To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added ammonium triflate salt (135.5 mg, 0.5 mmol, 1.0 equiv.) and Pd(OAc)2(112.25 mg, 0.5 mmol, 1.0 equiv.). After adding acetonitrile (5 mL) the tube was sealed and the solution was stirred at 80 °C for 4 h. The reaction mixture was filtered through a pad of celite topped with a layer of Na2CO3 and washed with CH3CN. The resulting filtrate was concentrated with the aid of a rotary evaporator, and a mixture of diethyl ether and n-pentane was added. The precipitate was vigorously stirred for 10 min, and the suspension was filtered. The solid residue was washed with n-pentane and dried under vacuum to afford the desired Pd-complex 4 as a brown solid (351 mg, 93% yield) [1H and13C matched with reference- Vicente, J.; Saura-Llamas, I.; Oliva-Madrid, M.-J.; García-López, J.-A.; Bautista, D. A New Method for High-Yield Cyclopalladation of Primary and Secondary Amines. Atom-Efficient Open-to-Air Inexpensive Synthesis of Buchwald-Type Precatalysts. Organometallics 2011, 30, 17, 4624–4631]. Synthesis of phosphino palladacyclic complex 5 To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added dimeric Pd-complex 4 (18.77 mg, 0.025 mmol, 1.0 equiv.) and ligand L1 (23.3 mg, 0.05 mmol, 2.0 equiv.). The tube was sealed, and evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous DCM (1 mL) was added via syringe and then the reaction mixture was allowed to stir for 30 min at room temperature. Then the solvent was removed with the aid of a rotary evaporator and n-pentane was added. The mixture was sonicated for 10 min and filtered. The solid residue was washed with n-pentane three times and dried under vacuum to afford the corresponding phosphino palladacyclic complex 5 as a yellow powder (48 mg, 96% yield).1H NMR (500 MHz, CDCl3) δ 7.59 (s, 1H), 7.41 – 7.29 (m, 2H), 7.09 – 6.86 (m, 6H), 6.17 – 5.95 (m, 2H), 3.14 (s, 6H), 2.93 (s, 6H), 2.58 – 2.37 (m, 4H), 2.03 – 1.73 (m, 6H), 1.67 – 1.48 (m, 5H), 1.42 – 1.04 (m, 11H).31P NMR (202 MHz, CDCl3) δ 38.86. Synthesis of phosphino palladacyclic complex 6 To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added dimeric Pd-complex 4 (18.77 mg, 0.025 mmol, 1.0 equiv.) and ligand L3 (21.22 mg, 0.05 mmol, 2 equiv.). The tube was sealed, and evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous DCM (1 mL) was added via syringe and then the reaction mixture was allowed to stir for 30 min at room temperature. Then the solvent was removed with the aid of a rotary evaporator and n-pentane was added. The mixture was sonicated for 10 min and filtered. The solid residue was washed with n-pentane and dried under vacuum to afford the corresponding phosphino palladacyclic complex 6 as a yellow powder (38 mg, 95% yield).31P NMR (202 MHz, CDCl3) δ 33.75, 28.90. Example 8: Synthesis of Pd-Precatalysts 8 and 9 Step 1: Synthesis of 2-ammoniumbiphenyl chloride To an oven-dried 100 mL round bottom flask equipped with a magnetic stir bar was added [1,1'-biphenyl]-2-amine (1.7 g, 10.0 mmol, 1 equiv.) and diethyl ether (35 mL). A solution of hydrochloric acid (0.64 mL, 10.0 mmol, 1.0 equiv.) in diethyl ether (5 mL) was added slowly and the mixture was allowed to stir for 30 min at room temperature. Then the reaction mixture was filtered, washed with diethyl ether (three times) and dried under vacuum to provide 2- ammoniumbiphenyl chloride as a white solid [1H and13C matched with reference- Bruno, N. C.; Tudge, M. T.; Buchwald, S. L. Design and preparation of new palladium precatalysts for C–C and C–N cross-coupling reactions. Chem. Sci. 2013, 4, 916–920]. Step 2: Synthesis of chloride bridge palladacyclic dimer 7 To an oven-dried 100 mL round bottom flask equipped with a magnetic stir bar and fitted with a teflon septum was added 2-ammoniumbiphenyl chloride (410.1 mg, 2.0 mmol, 1 equiv.), Pd(OAc)2 (448.0 mg, 2.0 mmol, 1 equiv.), and then evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous acetonitrile (10 mL) was added and the mixture was stirred at 40 °C for overnight until it became off-white in appearance. Then the reaction mixture was cooled to room temperature and the suspension was filtered, washed with diethyl ether (10 mL) and n-pentane (3 × 5 mL). The resulting residue was dried under vacuum for 24 hours to provide the title compound as an off-white to tan solid [1H and13C matched with reference- Bruno, N. C.; Tudge, M. T.; Buchwald, S. L. Design and preparation of new palladium precatalysts for C–C and C–N cross-coupling reactions. Chem. Sci.2013, 4, 916–920]. Synthesis of phosphino palladacyclic complex 8 To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added chloride bridge dimeric complex 7 (33.9 mg, 0.05 mmol, 0.5 equiv.), and ligand L1 (1.0 equiv.). The tube was sealed and evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous THF (3 mL) was added via syringe and then the reaction mixture was allowed to stir for 30 min at room temperature. After completion of the reaction, stir bar was removed and almost 90% of solvent was removed under vacuum at room temperature. The residue was then triturated with pentane. The resulting yellowish orange solid was filtered and dried under vacuum to afford the corresponding phosphino palladacyclic complex 8 as an orange solid.31P NMR (162 MHz, CDCl3) δ 41.33. Synthesis of phosphino palladacyclic complex 9 To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added chloride bridge dimeric complex 7 (33.9 mg, 0.05 mmol, 0.5 equiv.), and ligand L3 (1.0 equiv.). The tube was sealed and evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous THF (3 mL) was added via syringe and then the reaction mixture was allowed to stir for 30 min at room temperature. After completion of the reaction, stir bar was removed and almost 90% of solvent was removed under vacuum at room temperature. The residue was then triturated with pentane. The resulting brick red solid was filtered and dried under vacuum to afford the corresponding phosphino palladacyclic complex 9 as a brick red powder.31P NMR (202 MHz, CDCl3) δ 41.64, 35.72. Example 9: Synthesis of Pd-Precatalysts 11 and 12 Step 1: Synthesis of 2-ammoniumbiphenyl mesylate To an oven-dried 100 mL round bottom flask equipped with a magnetic stir bar was added [1,1'-biphenyl]-2-amine (1.7 g, 10.0 mmol, 1.0 equiv.) and diethyl ether (35 mL). A solution of methanesulfonic acid (0.64 mL, 10.0 mmol, 1.0 equiv.) in diethyl ether (5 mL) was added slowly and the mixture was allowed to stir for 30 min at room temperature. Then the reaction mixture was filtered, washed with diethyl ether (three times) and dried under vacuum to provide 2- ammoniumbiphenyl mesylate as a white solid (2.5 g, 96% yield) [1H and 13C matched with reference- Bruno, N. C.; Tudge, M. T.; Buchwald, S. L. Design and preparation of new palladium precatalysts for C–C and C–N cross-coupling reactions. Chem. Sci.2013, 4, 916–920]. Step 2: Synthesis of mesylate bridge palladacyclic dimer 10 To an oven-dried 100 mL round bottom flask equipped with a magnetic stir bar and fitted with a teflon septum was added 2-ammoniumbiphenyl mesylate (265.33 mg, 1.0 mmol, 1.0 equiv.), Pd(OAc)2 (224 mg, 1.0 mmol, 1.0 equiv.), and then evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous toluene (10 mL) was added and the mixture was stirred at 50 °C for 1 h until it became off-white in appearance. Then the reaction mixture was cooled to room temperature and the suspension was filtered, washed with toluene (10 mL) and diethyl ether (3 × 5 mL). The resulting residue was dried under vacuum for 24 hours to provide the title compound as an off-white solid (688 mg, 93% yield) [1H and13C matched with reference- Bruno, N. C.; Tudge, M. T.; Buchwald, S. L. Design and preparation of new palladium precatalysts for C–C and C–N cross- coupling reactions. Chem. Sci.2013, 4, 916–920]. Synthesis of phosphino palladacyclic complex 11 To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added μ-mesylate dimer 10 (185 mg, 0.25 mmol, 0.5 equiv.), and ligand L1 (218.3 mg, 0.5 mmol, 1.0 equiv.). The tube was sealed and evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous THF (4 mL) was added via syringe and then the reaction mixture was allowed to stir for 30 min at room temperature. After completion of the reaction, solvent was removed under vacuum at room temperature and n-pentane was added. The mixture was sonicated for 10 min, filtered and dried under vacuum to afford the corresponding phosphino palladacyclic complex 11 as an off-white solid (188 mg, 89% yield).1H NMR (400 MHz, CDCl3) δ 7.53 – 7.47 (m, 1H), 7.34 – 7.29 (m, 2H), 7.26 – 7.20 (m, 2H), 7.17 – 7.11 (m, 4H), 7.07 (t, J = 7.4 Hz, 2H), 7.01 – 6.94 (m, 2H), 6.27 (d, J = 2.4 Hz, 1H), 6.19 (dd, J = 8.7, 2.4 Hz, 1H), 3.25 (s, 6H), 2.58 (s, 6H), 2.47 (s, 3H), 2.06 – 1.91 (m, 8H), 1.88 – 1.79 (m, 3H), 1.67 – 1.54 (m, 2H), 1.50 – 1.35 (m, 4H), 0.98 – 0.81 (m, 2H), 0.80 – 0.64 (m, 3H).13C NMR (101 MHz, CDCl3) δ 160.78, 155.71, 152.07, 151.89, 146.23, 146.21, 140.57, 140.32, 137.49, 137.46, 136.91, 136.84, 133.09, 131.71, 131.68, 131.65, 131.53, 131.27, 130.91, 129.89, 127.79, 127.58, 127.55, 127.33, 126.94, 126.60, 126.28, 126.23, 125.10, 120.94, 100.56, 95.28, 92.49, 92.46, 68.10, 43.00, 40.67, 39.43, 36.09, 35.78, 32.64, 32.42, 32.17, 32.13, 28.40, 28.36, 28.10, 27.96, 27.89, 27.45, 27.37, 26.95, 26.84, 26.67, 26.53, 26.20, 26.11, 25.74, 25.70.31P NMR (162 MHz, CDCl3) δ 41.11. Synthesis of phosphino palladacyclic complex 12 To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added μ-mesylate dimer 10 (185 mg, 0.25 mmol, 0.5 equiv.), and ligand L3 (212.3 mg, 0.5 mmol, 1.0 equiv.). The tube was sealed and evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous THF (4 mL) was added via syringe and then the reaction mixture was allowed to stir for 30 min at room temperature. After completion of the reaction, solvent was removed under vacuum at room temperature and n-pentane was added. The mixture was sonicated for 10 min, filtered and dried under vacuum to afford the corresponding phosphino palladacyclic complex 12 as a yellow solid (172.7 mg, 87% yield).31P NMR (202 MHz, CDCl3) δ 39.61, 35.29. Example 10: Synthesis of Pd-Precatalysts 14 and 15 Step 1: Synthesis of N-Methyl-2-aminobiphenyl To an oven-dried 100 mL round bottom flask equipped with a magnetic stir bar was added 2-aminobiphenyl (1.7 g, 10.0 mmol, 1.0 equiv.) and capped with a rubber septum. The flask was evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous THF (25 mL) was added and the reaction mixture was cooled to 0 °C in an ice bath. n-BuLi (2.5 M in hexanes, 4.2 mL, 10.5 mmol, 1.05 equiv.) as added in a dropwise fashion and the bright yellow coloured reaction mixture was stirred for 1 h at 0 °C. Then MeI (0.63 mL, 10 mmol, 1.0 equiv.) was added slowly at 0 °C and the resulting faded yellow colour solution was stirred at room temperature for additional 30 min. After completion, the reaction mixture was quenched with saturated NaHCO3(aq) solution and transferred into a separating funnel. The aqueous layer was extracted with diethyl ether (3 × 15 mL), filtered, and the combined organic layers were dried over Na2SO4. After removal of solvent with the aid of a rotary evaporator, the crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 96:4) to give N-Methyl-2-aminobiphenyl as a light yellow oil (1.6 g, 89% yield) [1H and13C matched with reference- Bruno, N. C.; Niljianskul, N.; Buchwald, S. L. N-Substituted 2-Aminobiphenylpalladium Methanesulfonate Precatalysts and Their Use in C−C and C−N Cross-Couplings. J. Org. Chem. 2014, 79, 4161−4166]. Step 2: Synthesis of sulfonate bridge palladacyclic dimer 13 To an oven-dried 100 mL round bottom flask equipped with a magnetic stir bar was added N-Methyl-2-aminobiphenyl (183.1 mg, 1.0 mmol, 1.0 equiv.) and capped with a rubber septum. The flask was evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous THF (5 mL) followed by methanesulfonic acid was added dropwise and then the reaction mixture was stirred at room temperature for 30 min. Palladium acetate was added in one portion under the continuous flow of argon and the flask was capped with a rubber septum. The reaction mixture was stirred at 50 °C for 45 min. Then the mixture was cooled to room temperature and filtered through a plug of cotton to remove traces of palladium black. Almost 90% of the filtrate was evaporated and then diethyl ether was added to the flask. The mixture was sonicated to precipitate the product, filtered, and dried under vacuum for overnight to provide the corresponding dimeric palladacyclic complex 13 (390 mg) as an off white solid [1H and13C matched with reference- Bruno, N. C.; Niljianskul, N.; Buchwald, S. L. N-Substituted 2-Aminobiphenylpalladium Methanesulfonate Precatalysts and Their Use in C−C and C−N Cross-Couplings. J. Org. Chem. 2014, 79, 4161−4166]. Synthesis of phosphino palladacyclic complex 14 To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added dimeric Pd-complex 13 (390 mg, 0.05 mmol, 0.5 equiv.) and ligand L1 (430 mg, 1.0 mmol, 1 equiv.). The tube was sealed, and evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous DCM (10 mL) was added via syringe and then the reaction mixture was allowed to stir for 1 h at room temperature. Then the solvent was removed with the aid of a rotary evaporator and n-pentane was added. The mixture was vigorously stirred for 10 min and filtered. The solid residue was washed with n-pentane and dried under vacuum to afford the corresponding phosphino palladacyclic complex 14 as a yellow solid (749 mg, 92% yield).31P NMR (162 MHz, CDCl3) δ 42.81. Synthesis of phosphino palladacyclic complex 15 To an oven-dried Teflon screw-cap reaction tube equipped with a magnetic stir bar was added dimeric Pd-complex 13 (390 mg, 0.05 mmol, 0.5 equiv.) and ligand L3 (430 mg, 1.0 mmol, 1 equiv.). The tube was sealed, and evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous DCM (10 mL) was added via syringe and then the reaction mixture was allowed to stir for 1 h at room temperature. Then the solvent was removed with the aid of a rotary evaporator and n-pentane was added. The mixture was vigorously stirred for 10 min and filtered. The solid residue was washed with n-pentane and dried under vacuum to afford the corresponding phosphino palladacyclic complex 15 as an orange solid (749 mg, 92% yield).31P NMR (162 MHz, CDCl3) δ 40.30, 36.30. Example 11: Synthesis of 2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)pyridine Following the general procedure A, a mixture of 4-iodo-1-methyl-1H-pyrazole (41.6 mg, 0.2 mmol), 4-bromo-2-methoxypyridine (37.6 mg, 0.2 mmol), Pd(OAc)2 (2.24 mg, 5.0 mol%), L1 (8.7 mg, 10.0 mol%), Cs2CO3 (195.5 mg, 3.0 equiv.) was stirred and irradiated with a 456 nm blue LED for 24 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 60:40) to give the title compound as a reddish brown solid (32.5 mg, 86% yield). 1H NMR (500 MHz, CDCl3) δ 8.03 (d, J = 5.3 Hz, 1H), 7.74 (s, 1H), 7.60 (s, 1H), 6.87 (dd, J = 5.4, 1.6 Hz, 1H), 6.72 (s, 1H), 3.87 (s, 3H), 3.85 (s, 3H).13C NMR (126 MHz, CDCl3) δ 164.88, 147.22, 142.68, 137.11, 127.94, 120.58, 113.82, 106.07, 53.33, 39.14. Example 12: Synthesis of methyl 5-(2-(methoxycarbonyl)-4- methylphenyl)nicotinate Following the general procedure A, a mixture of methyl 2-iodo-5-methylbenzoate (55.2 mg, 0.2 mmol), methyl 5-bromonicotinate (43.2 mg, 0.2 mmol), Pd(OAc)2(2.24 mg, 5.0 mol%), L1 (8.7 mg, 10.0 mol%), Cs2CO3(195.5 mg, 3.0 equiv.) was stirred and irradiated with a 456 nm blue LED for 24 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 80:20) to give the title compound as a reddish sticky liquid (41 mg, 72% yield).1H NMR (500 MHz, CDCl3) δ 9.18 (d, J = 2.0 Hz, 1H), 8.67 (d, J = 2.2 Hz, 1H), 8.23 (t, J = 2.1 Hz, 1H), 7.82 (s, 1H), 7.41 (d, J = 9.6 Hz, 1H), 7.23 (d, J = 7.8 Hz, 1H), 3.96 (s, 3H), 3.67 (s, 3H), 2.45 (s, 3H).13C NMR (126 MHz, CDCl3) δ 167.91, 165.97, 152.94, 149.32, 138.76, 137.25, 136.84, 135.66, 132.91, 131.48, 131.17, 129.97, 125.40, 52.58, 52.22, 21.16. Example 13: Synthesis of methyl 2-methyl-5-(pyrimidin-5-yl)benzoate Following the general procedure A, a mixture of methyl 5-iodo-2-methylbenzoate (55.2 mg, 0.2 mmol), 5-bromopyrimidine (31.7 mg, 0.2 mmol), Pd(OAc)2 (2.24 mg, 5.0 mol%), L3 (8.5 mg, 10.0 mol%), 1,2,2,6,6-pentamethylpiperidine (116 μL, 3.0 equiv.) was stirred and irradiated with a 456 nm blue LED for 24 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 80:20) to give the title compound as a yellow sticky liquid (34 mg, 75% yield). 1H NMR (500 MHz, CDCl3) δ 9.21 (s, 1H), 8.97 (s, 2H), 8.14 (s, 1H), 7.62 (d, J = 10.2 Hz, 1H), 7.41 (d, J = 7.9 Hz, 1H), 3.94 (s, 3H), 2.67 (s, 3H).13C NMR (126 MHz, CDCl3) δ 167.54, 157.71, 154.91, 141.37, 133.56, 133.10, 131.96, 130.86, 130.21, 129.20, 52.29, 21.66. Example 14: Synthesis of 3-(benzofuran-5-yl)pyridine Following the general procedure A, a mixture of 3-bromopyridine (31.6 mg, 0.2 mmol), 5- bromobenzofuran (39.4 mg, 0.2 mmol), Pd(OAc)2 (2.24 mg, 5.0 mol%), L1 (8.7 mg, 10.0 mol%), N,N-diisopropylethylamine (110.7 μL, 3.0 equiv.) was stirred and irradiated with a 456 nm blue LED for 24 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 80:20) to give the title compound as a reddish sticky liquid (25.3 mg, 65% yield).1H NMR (400 MHz, CDCl3) δ 8.88 (s, 1H), 8.58 (d, J = 4.9 Hz, 1H), 7.92 – 7.87 (m, 1H), 7.79 (d, J = 1.9 Hz, 1H), 7.68 (d, J = 2.3 Hz, 1H), 7.60 (d, J = 8.5 Hz, 1H), 7.50 (dd, J = 8.5, 2.0 Hz, 1H), 7.37 (dd, J = 7.9, 5.8 Hz, 1H), 6.84 (dd, J = 2.2, 1.1 Hz, 1H).13C NMR (101 MHz, CDCl3) δ 155.03, 148.66, 148.20, 146.06, 137.26, 134.81, 133.08, 128.38, 123.93, 123.69, 120.04, 112.09, 106.90. Example 15: Synthesis of methyl 5-(3,4,5-trifluorophenyl)nicotinate Following the general procedure A, a mixture of 1,2,3-trifluoro-5-iodobenzene (51.5 mg, 0.2 mmol), 5- methyl 5-bromonicotinate (43.2 mg, 0.2 mmol), Pd(OAc)2 (2.24 mg, 5.0 mol%), L1 (8.7 mg, 10.0 mol%), Cs2CO3 (195.5 mg, 3.0 equiv.) was stirred and irradiated with a 456 nm blue LED for 24 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 90:10) to give the title compound as a white solid (36.8 mg, 69% yield).1H NMR (500 MHz, CDCl3) δ 9.23 (s, 1H), 8.92 (s, 1H), 8.41 (s, 1H), 7.28 – 7.15 (m, 2H), 4.00 (s, 3H).13C NMR (126 MHz, CDCl3) δ 165.46, 152.99, 152.96, 152.91, 152.88, 151.47, 150.99, 150.96, 150.88, 150.53, 141.44, 141.31, 139.41, 139.29, 139.17, 135.27, 133.86, 132.97, 132.93, 132.87, 126.39, 111.72, 111.68, 111.59, 111.55, 52.84.19F NMR (471 MHz, CDCl3) δ -132.43, -132.45, -132.47, -132.49. Example 16: Synthesis of [1,1'-biphenyl]-4-yl(phenyl)methanone Following the general procedure A, a mixture of iodobenzene (22.6 µL, 0.2 mmol), (4-bromophenyl)(phenyl)methanone (52.2 mg, 0.2 mmol), Pd(OAc)2 (2.24 mg, 5.0 mol%), L1 (8.7 mg, 10.0 mol%), Cs2CO3(195.5 mg, 3.0 equiv.) was stirred and irradiated with a 456 nm blue LED for 24 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 95:5) to give the title compound as a white solid (30.9 mg, 60% yield).1H NMR (500 MHz, CDCl3) δ 7.90 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 7.0 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 7.0 Hz, 2H), 7.61 (t, J = 7.5 Hz, 1H), 7.53 – 7.46 (m, 4H), 7.41 (t, J = 7.4 Hz, 1H).13C NMR (126 MHz, CDCl3) δ 196.56, 145.40, 140.14, 137.91, 136.38, 132.54, 130.88, 130.15, 129.12, 128.46, 128.34, 127.46, 127.12. 1H-pyrazol-4-yl)pyridin-2- Following the general procedure A, a mixture of 4-bromo-1-methyl-1H-pyrazole (32.2 mg, 0.2 mmol), tert-butyl (5-iodopyridin-2-yl)carbamate (64 mg, 0.2 mmol), Pd(OAc)2(2.24 mg, 5.0 mol%), L1 (8.7 mg, 10.0 mol%), Cs2CO3(195.5 mg, 3.0 equiv.) was stirred and irradiated with a 456 nm blue LED for 24 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 70:30) to give the title compound as a yellow solid (31.8 mg, 58% yield).1H NMR (500 MHz, CDCl3) δ 8.31 (d, J = 2.4 Hz, 1H), 8.11 (d, J = 8.7 Hz, 1H), 7.91 (s, 1H), 7.71 (dd, J = 8.7, 2.4 Hz, 1H), 7.54 (s, 1H), 3.82 (s, 3H), 1.54 (s, 9H).13C NMR (126 MHz, CDCl3) δ 152.66, 152.38, 148.67, 139.52, 138.26, 119.33, 112.13, 94.31, 81.75, 38.47, 28.39. Following the general procedure A, a mixture of 1-bromo-4-fluorobenzene (35 mg, 0.2 mmol), methyl 4-iodobenzoate (52.41 mg, 0.2 mmol), Pd(OAc)2(2.24 mg, 5.0 mol%), L1 (8.7 mg, 10.0 mol%), Cs2CO3 (195.5 mg, 3.0 equiv.) was stirred and irradiated with a 456 nm blue LED for 24 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 95:5) to give the title compound (28 mg, 61% yield).1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.8 Hz, (m, 4H), 7.15 (t, J = 8.7 Hz, 2H), 3.94 (s, 3H).13C NMR (126 167.07, 164.07, 162.10, 144.74, 136.25, 130.30, 129.09, 129.06, 116.10, 115.92, 52.29. of 2,2'-dimethoxy-1,1'-biphenyl procedure A, a mixture of 1-iodo-2-methoxybenzene (93.6 Pd(OAc)2(2.24 mg, 5.0 mol%), L1 (8.7 mg, 10.0 mol%), Cs2CO3was stirred and irradiated with a 456 nm blue LED for 24 h. was purified by flash column chromatography (Petroleum 96:4) to give the title compound as a white solid (33.6 mg, 80% (500 MHz, CDCl3) δ 7.39 – 7.35 (m, 2H), 7.29 (dd, J = 7.4, 1.8 J = 7.3, 1.1 Hz, 2H), 7.02 (d, J = 8.2 Hz, 2H), 3.81 (s, 6H).13C CDCl3) δ 157.17, 131.60, 128.74, 127.96, 120.48, 111.24, 55.83. Example 20: Synthesis of 5,5'-dimethyl-2,2'-bipyridine Following the general procedure A, a mixture of 2-bromo-5-methylpyridine (68.8 mg, 0.4 mmol), Pd(OAc)2 (2.24 mg, 5.0 mol%), L1 (8.7 mg, 10.0 mol%), Cs2CO3 (195.5 mg, 3.0 equiv.) was stirred and irradiated with a 456 nm blue LED for 24 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 80:20) to give the title compound as a white solid (31.2 mg, 85% yield).1H NMR (400 MHz, CDCl3) δ 8.48 (s, 2H), 8.23 (d, J = 8.1 Hz, 2H), 7.60 (dd, J = 8.2, 2.3 Hz, 2H), 2.38 (s, 6H).13C NMR (101 MHz, CDCl3) δ 153.94, 149.68, 137.55, 133.15, 120.48, 18.44. Example 21: Synthesis of 2,2',4,6'-tetramethyl-1,1'-biphenyl Following the general procedure B, a mixture of 2-bromo-1,3-dimethylbenzene (37.0 mg, 0.2 mmol), (2,4-dimethylphenyl)boronic acid (35.9 mg, 0.24 mmol), Pd(OAc)2 (0.4 mg, 1 mol%), L1 (1.7 mg, 2 mol%), K3PO4 (84.9 mg, 2.0 equiv.) was stirred at 60 °C for 10 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 100:0) to give the title compound as a colorless liquid (39.9 mg, 95% yield).1H NMR (500 MHz, CDCl3) δ 7.21 – 7.17 (m, 1H), 7.16 – 7.13 (m, 3H), 7.10 (d, J = 9.5 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 2.42 (s, 3H), 2.00 (s, 6H), 1.98 (s, 3H).13C NMR (126 MHz, CDCl3) δ 141.24, 137.66, 136.53, 136.21, 135.48, 130.89, 128.84, 127.29, 126.93, 126.90, 21.31, 20.52, 19.46. Example 22: Synthesis of 2',6'-diisopropyl-2,4-dimethyl-1,1'-biphenyl Following the general procedure B, a mixture of 2-iodo-1,3-diisopropylbenzene (48.2 mg, 0.2 mmol), (2,4-dimethylphenyl)boronic acid (35.9 mg, 0.24 mmol), Pd(OAc)2(0.4 mg, 1 mol%), L1 (1.7 mg, 2 mol%), K3PO4(84.9 mg, 2.0 equiv.) was stirred at 60 °C for 10 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 100:0) to give the title compound as a colorless liquid (38.3 mg, 72% yield).1H NMR (500 MHz, CDCl3) δ 7.34 (t, J = 7.8 Hz, 1H), 7.20 (d, J = 7.8 Hz, 2H), 7.09 (s, 1H), 7.03 (d, J = 7.6 Hz, 1H), 6.92 (d, J = 7.6 Hz, 1H), 2.47 (hept, J = 6.9 Hz, 2H), 2.38 (s, 3H), 1.95 (s, 3H), 1.11 (d, J = 6.9 Hz, 6H), 1.02 (d, J = 6.9 Hz, 6H).13C NMR (126 MHz, CDCl3) δ 146.92, 138.56, 136.98, 136.49, 136.23, 130.57, 129.88, 127.74, 126.32, 122.75, 30.41, 25.02, 23.58, 21.35, 20.28. Example 23: Synthesis of 4-methyl-2-(piperidin-1-yl)pyridine Following the general procedure C, a mixture of 4-methylpyridin-2-yl trifluoromethanesulfonate (48.2 mg, 0.2 mmol), piperidine (22.1 mg, 0.26 mmol), Pd(OAc)2(0.4 mg, 1 mol%), L1 (1.7 mg, 2 mol%), NaOtBu (38.4 mg, 2.0 equiv.) was stirred at 110 °C for 12 h. The crude material was purified by flash column chromatography (Petroleum ether:EtOAc = 95:5) to give the title compound as a colorless liquid (32.4 mg, 92% yield).1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 5.2 Hz, 1H), 6.47 (s, 1H), 6.41 (d, J = 5.1 Hz, 1H), 3.54 – 3.45 (m, 4H), 2.24 (s, 3H), 1.65 – 1.61 (m, 6H). The present invention is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention, in addition to those described herein, will become apparent to those skilled in the art from the foregoing description and accompanying figures. Such modifications are intended to fall within the scope of the appended claims. The invention is, therefore, to be limited only by the terms of the appended claims along with the full scope of equivalents to which the claims are entitled.

Claims

CLAIMS:

1. A ligand represented by I:Wherein R can be selected independently from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and –(CH2)m-R10; R1, R2, R3, and R4can be selected independently from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and -OR11; or any two adjacent instances of R1, R2, R3and R4can form a five- or six-membered substituted or unsubstituted aryl or heteroaryl ring; R5, R6and R8can be selected independently from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, -OH, -OR12, -NH2, -NHR13, and -N(R14)2; R5and R6can form a five- or six-membered substituted or unsubstituted aryl or heteroaryl ring; R7and R9are selected independently from the group of -N(R14)2; R10, R11, R12, R13, and R14are selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, and heteroaralkyl; m can be an integer in the range 0 to 8.

2. The ligand of claim 1, wherein R is iso-propyl (i-Pr).

3. The ligand of claim 1, wherein R is cyclohexyl (Cy).

4. The ligand of claim 1, wherein R is phenyl (Ph).

5. The ligand of claim 1, wherein R1, R2, R3, and R4are hydrogen.

6. The ligand of claim 1, wherein R5, R6, and R8are hydrogen.

7. The ligand of claim 1, wherein R7and R9are NMe2.

8. A ligand selected from the group consisting of:

9. A process for preparing the ligands, the process comprising the steps: a. reacting bromo-2,4-dinitrobenzene and (2-bromophenyl)boronic acid in presence of NaHCO3and Pd(PPh3)4in a solvent mixture of DME and H2O (2:1) at 110 °C for 8 h to obtain 2'-bromo-2,4-dinitro-1,1'-biphenyl; b. reacting 2'-bromo-2,4-dinitro-1,1'-biphenyl with NH4Cl in presence of Fe powder iniPrOH and H2O for 2h and cooled to room temperature to obtain 2'-bromo-[1,1'-biphenyl]-2,4-diamine; c. reacting 2'-bromo-[1,1'-biphenyl]-2,4-diamine with MeI in presence of sodium hydride in THF at room temperature for 9h to obtain 2'-bromo- N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine; d. mixing 2'-bromo-N2,N2,N4,N4-tetramethyl-[1,1'-biphenyl]-2,4-diamine with THF and n-BuLi for 40 min at -78 °C; and e. adding a regent selected from Cy2PCl,iPr2PCl or Ph2PCl to the reaction mixture of step (d) at -78 °C to obtain the ligand.

10. A phosphino palladacyclic complex as precatalyst selected from the group consisting of:

11. A method of cross-Ullmann coupling represented by the following reaction:Wherein P can be selected from the group consisting of substituted or unsubstituted aryl and heteroaryl; Z can be selected from the group consisting of substituted or unsubstituted aryl and heteroaryl;Q can be selected from the group consisting of -I, -Br, -Cl, -OSO2R'; Y can be selected from the group consisting of -I, -Br, -Cl, -OSO2R'; R' is selected from the group consisting of alkyl, perfluoroalkyl, aryl, and heteroaryl; transition metal can be selected from the group consisting of Ni and Pd; the ligand is selected from the group consisting of the ligands of claims 1-8; the base can be selected from the group consisting of hydrides, fluorides, hydroxides, carbonates, phosphates, alkoxides, metal amides, and carbanions; solvent can be selected from the group consisting of acetonitrile, toluene, acetone, and THF.

12. The method of claim 10, wherein the period of time is from 12 h to 24 h.

13. The method of claim 10, wherein the temperature is about 35 °C to 40 °C (room temperature).

14. The method of claim 10, wherein the light source is either 440 nm or 456 nm blue LED.

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