SELECTIVE MONOARYLATIONS OF HYDRAZINES

Abstract

The present invention is directed towards the monoarylation of hydrazines. In particular, a process is described herein to selectively add aryls or hetero aryls to hydrazine via a CN-cross-coupling reaction using special Pd-phosphine complexes.

Claims

1. Process for the selective monoarylation of hydrazine hydrate or hydrazine salts of the general formular (I) or (II): ##STR00023## wherein W is a counter anion which comprises the steps of: providing an organic polar solvent, which does not interact with the reactants added but dissolves the reactants; adding thereto as a reactant a hydrazine of formula (I) or (II); adding a catalyst of the general formula (III) or (IV): ##STR00024## wherein R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; R8 is an alkenyl, aryl or aryl alkenyl group; R.sub.A and R.sub.B are if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen, halogen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; and X is O or S, with O being preferred; Y is an anionic ligand; Z is a -donor ligand; adding as a further reactant an aryl halide or heteroaryl halide to the reaction mixture; and adding a base; and isolating the arylhydrazine from the reaction mixture.

2. Process according to claim 1, wherein R1 is methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl and sec-butyl, R2 is methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl and sec-butyl, R3 is tert-butyl, isopropyl or 1-adamantyl, propellane, R4 is tert-butyl, isopropyl or 1-adamantyl, propellane; R5 is methyl, ethyl, propyl, isopropyl, butyl, iso-butyl and sec-butyl, R6 methyl, ethyl, propyl, isopropyl, butyl, iso-butyl and sec-butyl, R7 is methyl, ethyl, propyl, isopropyl, butyl, iso-butyl and sec-butyl.

3. Process according to claim 1, wherein the aryl halide is selected from the group consisting of phenyl, naphthyl, pyridyl, pyrazinyl and thienyl.

4. Process according to claim 1, wherein the organic solvent is selected from the group consisting of THF, dioxane, DME, CPME, 2-MeTHF.

5. Process according to claim 1, wherein the base is selected from the group consisting of KOH, K.sub.2CO.sub.3, K.sub.3PO.sub.4, Cs.sub.2CO.sub.3, NaOtBu, KOtBu, NaOMe, NaOH.

6. Process according to claim 1, wherein the process is conducted at a temperature of 10 C. to 80 C.

7. Process according to claim 1, wherein the arylhydrazine is isolated by acidified by concentrated hydrochloride acid to generate the hydrochloride salts and purified by two-phase extractions, precipitation and filtration.

8. Process according to claim 1, wherein Z is a bidentate ligand in which one part of the ligand is connected to the Palladium via a -donor bond as mentioned before and the other part is connected to the Palladium via a heteroatomic substituent.

9. Catalyst for the monoarylation of hydrazines of general formula (IV) ##STR00025## wherein R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; R8 is an alkenyl, aryl or aryl alkenyl group; R.sub.A and R.sub.B are if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen, halogen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; and X is O or S, with O being preferred; Y is a an anionic ligand.

10. Process for the production of a compound according to claim 8, characterized in that a compound of general formula (VI) ##STR00026## wherein R, R, R are independently of each other selected from the group consisting of H, alkyl, aryl or R and R form an aromatic or non-aromatic cyclic ring; Y is a halide; and a ligand of formula (III) ##STR00027## wherein R1, R2 are same or different from each other and being linear or branched alkyl; R3, R4, are same or different from each other and being branched or cyclic alkyl; R5, R6, R7 are same or different from each other and being H, linear or branched or cyclic alkyl; R.sub.A and R.sub.B are if present independently from each other one or more alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, aralkyl, hydrogen, halogen, heteroaralkyl, alkoxyl, dialkylaminyl, trialkylsilyl; X is O or S; are reacted under conditions sufficient to produce the compound of the present claim.

Description

FIGURES

[0068] FIG. 1: ESI-MS spectrum of reaction mixture of [Pd(cinnamyl)(.sup.tBuBrettPhos)Cl] with 0.01 mmol [Pd(cinnamyl)Cl].sub.2, 2.0 equiv. .sup.tBuBrettPhos in 2 mL THF for 30 min at 80 C.

[0069] FIG. 2: ESI-MS spectrum of isolated [Pd(allyl)(.sup.tBuBrettPhos)Cl]following general procedure A in THF with 0.25 mmol [Pd(allyl)Cl].sub.2.

[0070] FIG. 3: Comparison of .sup.1H NMR spectra of [Pd(1-MeNAP)(tBuBrettPhos)Br](bottom), .sup.tBuBrettPhos (middle), and [Pd(1-MeNAP)Br].sub.2 (top). .sup.1H NMR spectra were recorded at 400 MHz in CD.sub.2Cl.sub.2 or DMSO-d.sub.6 (for [Pd(1-MeNAP)Br].sub.2 due to low solubility in DCM).

[0071] FIG. 4: Solid state structure of Pd(2-MeNAP)Br-.sup.tBuBrettPhos complex. Hydrogen atoms are omitted for clarity. The thermal ellipsoids are drawn at the 50% probability level. Disorder of 2-methylnaphthyl group was omitted for clarity.

[0072] FIG. 5: Solid state structure of Pd(1-MeNAP)Br-.sup.tBuBrettPhos complex. Hydrogen atoms are omitted for clarity. The thermal ellipsoids are drawn at the 50% probability level.

EXPERIMENTAL REPORT

I. General

[0073] All reactions were performed in oven-dried glassware containing a Teflon-coated stirring bar and dry septum under nitrogen atmosphere. Optimization reactions were monitored by .sup.19F NMR analysis using 1, 4-difluorobenzene as internal standard.

[0074] Characterization of the compounds was done by:

[0075] .sup.1H, .sup.13C{1H}, and .sup.31P NMR spectra were recorded on an Avance-III-300 or Avance-III-400 spectrometer at 25 C. if not stated otherwise. .sup.19F NMR spectra were recorded on Spinsolve Benchtop NMR (MAGRITEK) spectrometers at 25 C. All values of the chemical shift are in ppm regarding the 5-scale. To display multiplicities and signal forms correctly the following abbreviations were used: s=singlet, d=doublet, t=triplet, q=quartet, spt=septet, m=multiplet, dd=doublet of doublet, dq=doublet of quartet, dspt=doublet of septet, br=broad signal. Column chromatography was performed on a CombiFlash Companion (Isco) and a Pure C-815 Flash (Buchi) using Reveleris packed columns (12 g or 40 g). Mass spectrometric data (EI) were acquired on a GC-MS Agilent 5977B MSD. Mass spectra (ESI) of Pd complexes were recorded via direct injection using acetonitrile/water (0.1% formic acid) as eluent. Samples were prepared by dissolving the complex in acetonitrile (ca. 1 mg/mL) and filtration through a PTFE syringe filter. The evaluation and calculation of MS spectra were performed with the MassLynx software HRMS analyses were acquired using a GC-MS system consisting of an Agilent 7250 GC/Q-TOF, in which ionization was achieved by EI. Infrared spectra were recorded on Bruker Vertex 70 Spectrometer with Universal ATR Sampling Accessory. Melting points were measured on a Mettler Toledo MP70. Elemental analysis was performed on a varioMICRO CHNS.

[0076] Commercial substrates were used as received unless otherwise stated. Ammonium triflate was washed with ether, dried in vacuo, and stored in the glovebox. Solvents were purchased (puriss p.A.) from commercial suppliers and dried by standard procedures (Armarego, W. L. F.; Chai, C. L. L. Purification of Laboratory Chemicals, 5th ed.; Butterworth-Heinemann: Amsterdam; Boston, 2003). All solvents and liquid reactants were degassed by Argon purge prior to use. [Pd(1-MeNAP)Br].sub.2 as well as other Pd sources were donated by Umicore (EP4267591A). KOH pellets were imported into a glovebox and pulverized into a fine powder with a mortar and pestle. [N.sub.2H.sub.5][OTf] was synthesized by previously reported procedure (Mock, M. T.; Chen, S.; O'Hagan, M.; Rousseau, R.; Dougherty, W. G.; Kassel, W. S.; Bullock, R. M. Dinitrogen Reduction by a Chromium(0) Complex Supported by a 16-Membered Phosphorus Macrocycle. J. Am. Chem. Soc. 2013, 135 (31), 11493-11496).

II. Production of the Catalysts Tested

General Preparation of Pd Pre-CatalystsProcedure A

Catalysts of Formula (IV)

[0077] [Pd(MeNAP)Br].sub.2 (EP4267591A) (0.125 or 0.25 mmol) and ligand (2.0 equiv.) were weighed in an oven-dry vial. After addition of 5 or 10 mL THF or acetone, the reaction mixture was stirred at room temperature overnight. 90% of the solvent was evaporated and 5 or 10 mL pentane was added. The mixture was stored at 20 C. over night to crystallize the product. The mother liquor was decanted and the remaining solid was washed with pentane (35 mL) and dried under high vacuum to afford the Pd complex.

Catalysts of Formula (III) and (V):

[0078] The catalysts are commercially available under https://www.sigmaaldrich.com/DE/en/technical-documents/technical-article/chemistry-and-synthesis/cross-coupling/buchwald-g6-precatalysts-oxidative-addition-complexes or can be prepared as mentioned in: King, R.; Senecal, T. D.; Shu, W.; Buchwald, S. L. A General, Practical Palladium-Catalyzed Cyanation of (Hetero)Aryl Chlorides and Bromides. Angew. Chem. Int. Ed. 2013, 52 (38), 10035-10039.

III. Results on Generation of Pd Catalysts

2-di-tert-butylphosphino(2,4,6-triisopropyl-3,6-dimethoxy-4-(naphthalen-1-ylmethyl)-[1,1-biphenyl])bromo-palladium(II) [Pd(1-MeNAP)(tBuBrettPhos)Br]

##STR00009##

[0079] Following general procedure A with [Pd(1-MeNAP)Br].sub.2 (81.9 mg, 0.125 mmol) and .sup.tBuBrettPhos (122 mg, 0.25 mmol) in acetone, the title compound was obtained as yellow solid (169 mg, 0.208 mmol, 83%).

[0080] .sup.1H NMR (400 MHz, CD.sub.2Cl.sub.2): =8.61-8.59 (m, 1H), 7.80-7.70 (m, 2H), 7.44-7.36 (m, 4H), 6.93-6.87 (m, 2H), 5.04 (s, 1H), 5.03 (s, 1H), 4.21 (s, 2H), 3.80 (s, 3H), 3.66 (s, 3H), 1.93 (sept., J=6.8 Hz, 1H), 1.86-1.76 (m, 2H), 1.49 (d, J=14.9 Hz, 18H), 1.03 (d, J=6.9 Hz, 6H), 0.92 (d, J=6.6 Hz, 6H), 0.84 (d, J=6.7 Hz, 6H) ppm.

[0081] .sup.13C NMR (75 MHz, CD.sub.2Cl.sub.2): =155.7 (d, J=2.8 Hz), 151.2 (d, J=22.9 Hz), 140.0 (d, J=22.9 Hz), 136.3, 134.5 (d, J=6.0 Hz), 134.3 (d, J=4.5 Hz), 133.8 (d, J=15.5 Hz), 129.3, 128.4 (d, J=3.0 Hz), 127.2, 126.0, 125.6, 125.4, 113.9 (d, J=1.7 Hz), 112.3 (d, J=18.1 Hz), 111.4 (d, J=3.9 Hz), 92.3 (d, J=9.2 Hz), 55.0 (d, J=3.0 Hz), 54.8, 54.5, 50.6 (d, J=8.3 Hz), 43.8 (d, J=9.1 Hz), 38.4 (d, J=7.2 Hz), 32.2, 32.1 (d, J=7.7 Hz), 31.9, 31.0, 25.4, 23.4, 17.8 ppm.

[0082] .sup.31P NMR (162 MHz, CD.sub.2Cl.sub.2): =94.3, 84.3 ppm.

[0083] MS (ESI-TOF): m/z (%)=772.38 (2), 731.22 (100).

[0084] EA: Calc. for C.sub.42H.sub.58O.sub.2PBrPd: C, 62.11%; H, 7.20%; N, 0.00%; Found: C, 62.01%; H, 6.84%; N, 0.00%.

2-di-tert-butylphosphino(2,4,6-triisopropyl-3,6-dimethoxy-4-(naphthalen-2-ylmethyl)-[1,1-biphenyl])bromo-palladium(II) [Pd(2-MeNAP)(tBuBrettPhos)Br]

##STR00010##

[0085] Following general procedure A with [Pd(2-MeNAP)Br].sub.2 (166 mg, 0.25 mmol) and .sup.tBuBrettPhos (253 mg, 0.50 mmol) in THF, the title compound was obtained as yellow solid (287 mg, 0.353 mmol, 71%).

[0086] .sup.1H NMR (400 MHz, CD.sub.2Cl.sub.2): =7.80-7.78 (m, 1H), 7.75-7.73 (m, 1H), 7.68 (d, J=8.3 Hz, 1H), 7.62-7.59 (m, 1H), 7.45-7.36 (m, 2H), 7.30 (dt, J=8.6, 0.8 Hz, 1H), 6.81-6.72 (m, 2H), 5.63 (s, 1H), 5.61 (s, 1H), 3.73 (s, 3H), 3.02 (s, 3H), 2.98 (s, 2H), 2.43 (sept, J=6.8 Hz, 1H), 1.68-1.59 (m, 2H), 1.35 (d, J=14.9 Hz, 18H), 1.25 (d, J=6.9 Hz, 6H), 1.06 (d, J=6.7 Hz, 6H), 0.66 (d, J=6.6 Hz, 6H) ppm.

[0087] .sup.13C NMR (75 MHz, CD.sub.2Cl.sub.2): =155.3 (d, J=2.8 Hz), 151.1 (d, J=23.9 Hz), 140.1 (d, J=24.2 Hz), 137.0, 134.9 (d, J=6.0 Hz), 133.6, 133.6 (d, J=16.6 Hz), 132.7, 130.6, 129.7, 128.1, 127.9, 127.2, 126.1, 125.5, 113.7 (d, J=1.7 Hz), 113.5, 113.3, 111.1 (d, J=3.3 Hz), 100.6, 89.7 (d, J=10.0 Hz), 54.6, 53.9, 50.0 (d, J=7.5 Hz), 43.9 (d, J=10.6 Hz), 41.0 (d, J=18.9 Hz), 38.3 (d, J=7.2 Hz), 31.9 (d, J=7.2 Hz), 30.8, 24.4 (d, J=6.0 Hz), 18.9 ppm.

[0088] .sup.31P NMR (162 MHz, CD.sub.2Cl.sub.2): =85.2 ppm.

[0089] MS (ESI-TOF): m/z (%)=772.42 (13), 731.29 (100), 590.14(1), 485.24 (2).

2-diadamantylphosphino(2,4,6-triisopropyl-3,6-dimethoxy-4-(naphthalen-1-ylmethyl)-[1,1-biphenyl])bromo-palladium(II) [Pd(1-MeNAP)(AdBrettPhos)Br]

##STR00011##

[0090] Following general procedure A with [Pd(1-MeNAP)Br].sub.2 (81.9 mg, 0.125 mmol) and AdBrettPhos (169 mg, 0.25 mmol) in acetone, the title compound was obtained as yellow solid (195 mg, 0.201 mmol, 81%).

[0091] .sup.1H NMR (400 MHz, CD.sub.2Cl.sub.2): =8.58-8.55 (m, 1H), 7.81-7.71 (m, 2H), 7.46-7.33 (m, 4H), 6.90 (d, J=1.2 Hz, 2H), 5.06 (s, 1H), 5.04 (s, 1H), 4.22 (s, 2H), 3.84 (s, 3H), 3.65 (s, 3H), 2.29 (br. s, 12H), 2.01 (br. s, 6H), 1.85-1.71 (m, 15H), 1.03 (d, J=6.9 Hz, 6H), 0.93-0.91 (m, 12H) ppm.

[0092] .sup.13C NMR (75 MHz, CD.sub.2Cl.sub.2): =155.7 (d, J=2.2 Hz), 151.2 (d, J=23.4 Hz), 140.5 (d, J=23.8 Hz), 136.3, 134.4 (d, J=1.5 Hz), 134.3, 132.6 (d, J=13.8 Hz), 129.4, 128.4 (d, J=6.0 Hz), 127.2, 126.0, 125.7, 125.3, 113.6 (d, J=1.7 Hz), 112.3 (d, J=21.1 Hz), 111.1 (d, J=3.3 Hz), 92.2 (d, J=8.8 Hz), 55.0 (d, J=3.3 Hz), 54.8, 50.7 (d, J=8.3 Hz), 43.7, 43.5 (d, J=5.3 Hz), 42.3 (d, J=3.8 Hz), 37.2 (d, J=1.1 Hz), 32.0 (d, J=18.1 Hz), 29.9 (d, J=9.1 Hz), 25.4, 23.6, 17.8 ppm.

[0093] .sup.31P NMR (162 MHz, CD.sub.2Cl.sub.2): =100.3, 86.2 ppm. MS (ESI-TOF): m/z (%)=887.51 (32).

[0094] EA: Calc. for C.sub.54H.sub.70O.sub.2PBrPd: C, 66.97%; H, 7.29%; N, 0.00%; Found: C, 67.09%; H, 6.94%; N, 0.00%.

2-diadamantylphosphino(2,4,6-triisopropyl-3,6-dimethoxy-4-(naphthalen-2-ylmethyl)-[1,1-biphenyl])bromo-palladium(II) [Pd(2-MeNAP)(AdBrettPhos)Br]

##STR00012##

[0095] Following general procedure A with [Pd(2-MeNAP)Br].sub.2 (165 mg, 0.25 mmol) and AdBrettPhos (358 mg, 0.50 mmol) in THF, the title compound was obtained as yellow solid (375 mg, 0.387 mmol, 77%).

[0096] .sup.1H NMR (400 MHz, CD.sub.2Cl.sub.2): =7.80-7.73 (m, 2H), 7.69 (d, J=8.2 Hz, 1H), 7.62-7.59 (m, 1H), 7.45-7.36 (m, 2H), 7.30 (dd, J=8.4, 0.9 Hz, 1H), 6.82-6.71 (m, 2H), 5.61 (s, 1H), 5.59 (s, 1H), 3.77 (s, 3H), 3.03 (s, 3H), 2.98 (s, 2H), 2.51-2.38 (m, 1H), 2.20-2.11 (m, 12H), 1.89 (s, 6H), 1.69-1.59 (m, 14H), 1.27 (d, J=6.7 Hz, 6H), 1.08 (d, J=6.7 Hz, 6H), 0.65 (d, J=6.6 Hz, 6H) ppm.

[0097] .sup.13C NMR (75 MHz, CD.sub.2Cl.sub.2): =155.2 (d, J=2.2 Hz), 151.2 (d, J=23.6 Hz), 140.5 (d, J=23.6 Hz), 137.1, 135.1 (d, J=5.3 Hz), 133.6, 132.7, 132.3 (d, J=15.5 Hz), 130.6, 129.7, 128.1, 127.9, 127.2, 126.0, 125.5, 113.5 (d, J=1.9 Hz), 113.5, 113.3, 110.9 (d, J=3.9 Hz), 89.1 (d, J=9.4 Hz), 54.6, 53.8, 50.0 (d, J=8.3 Hz), 43.6 (d, J=9.8 Hz), 43.2 (d, J=5.5 Hz), 42.1 (d, J=3.3 Hz), 41.2 (d, J=18.9 Hz), 37.1 (d, J=1.1 Hz), 30.7, 29.8 (d, J=9.1 Hz), 24.4 (d, J=6.0 Hz), 19.0 ppm.

[0098] .sup.31P NMR (162 MHz, CD.sub.2Cl.sub.2): =86.4 ppm.

[0099] MS (ESI-TOF): m/z (%)=928.44 (22), 887.44 (100), 827.22 (7), 746.41 (2) 641.35 (11).

IV. General Procedure for the Arylation of Hydrazinium Triflate

[0100] An oven-dried vial was charged with [Pd(1-MeNAP)(.sup.tBuBrettPhos)Br](8.1 mg, 0.01 mmol, 1.0 mol %) and aryl chloride (1.0 mmol, 1.0 equiv., if solid), then KOH (253 mg, 4.5 mmol, 4.5 equiv.), [N.sub.2H.sub.5][OTf](364 mg, 2.0 mmol, 2.0 equiv.), aryl chloride (1.0 mmol, 1.0 equiv., if liquid) and 3 mL 1,4-Dioxane were added in the glovebox and the vial was closed with a septum cap. The resulting mixture was stirred at 25 C. for 16 h. Afterwards, acetylacetone (929 L, 9 mmol, 9.0 equiv) was added to the reaction and the mixture was stirred at 100 C. for 6 h. The reaction was then cooled to room temperature, diluted with EtOAc (30 mL), and washed with saturated NaHCO.sub.3 (30 mL), water (30 mL) and brine (30 mL). The organic phase was dried over MgSO.sub.4 and purified by flash column chromatography (SiO.sub.2, cyclohexane/ethyl acetate) to yield the products. Alternatively, the reaction mixture was diluted with diethyl ether after the reaction time of 16 h, and washed with saturated Na.sub.2CO.sub.3 (30 mL), water (30 mL) and brine (30 mL). And then the organic layer was separated and acidified to pH=3-4 by adding 37% HCl. The precipitate was filtered, washed with diethyl ether and dried under the vacuum to afford the corresponding aryl hydrazine hydrochloride salts.

V. Isolating and X-Ray of the Crystals of Catalyst (IV)

[0101] Single crystals of Pd(2-MeNAP)Br-.sup.tBuBrettPhos were grown by slow diffusion of n-hexane into a saturated solution of the complex in toluene. A crystal was taken up in perfluorinated oil and mounted onto a fiber loop on a Rigaku Oxford diffraction XtaLAB SuperNova diffractometer equipped with an Atlas CCD detector. The crystal was kept at 110.00(10) K during data collection. The obtained diffraction data was analyzed using CrysAlisPro software package. Using Olex2, the structure was solved with the ShelXT structure solution program using Intrinsic Phasing and refined with the ShelXL refinement package using Least Squares minimization (0. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, H. Puschmann, J. Appl. Crystallogr. 2009, 42, 339-341; G. M. Sheldrick, Acta Crystallogr. Sect. Found. Adv. 2015, 71, 3-8; G. M. Sheldrick, Acta Crystallogr. Sect. C Struct. Chem. 2015, 71, 3-8; P. Van Der Sluis, A. L. Spek, Acta Crystallogr A Found Crystallogr 1990, 46, 194-201).

[0102] Crystal data and structure refinement for Pd(2-MeNAP)Br-.sup.tBuBrettPhos complex:

TABLE-US-00001 Identification code paf1947b_auto_a.cif Empirical formula C37.33 H51.56 Br0.89 O1.78 P0.89 Pd0.89 Formula weight 721.92 Temperature 110(2) K Wavelength 1.54184 (Cu K) Crystal system monoclinic Space group C 2/c (no. 15) Unit cell dimensions a = 21.0683(3) = 90 b = 11.5672(2) = 91.5110(10) c = 31.8109(5) = 90 Volume 7749.7(2) .sup.3 Z 9 Density (calculated) 1.392 g/cm.sup.3 Absorption coefficient 5.709 mm.sup.1 F(000) 3376 Crystal size 0.344 0.136 0.098 mm.sup.3 Theta range for data collection 2.779 to 76.405 Index ranges 24 <= h <= 26, 7 <= k <= 14, 39 <= l <= 38 Reflections collected 25989 Independent reflections 7566 [R.sub.int = 0.0280, R.sub.sigma = 0.0260] Completeness to theta = 67.684 99.3% Absorption correction multi-scan Max. and min. transmission 1.00000 and 0.44247 Refinement method full-matrix least-squares on F.sup.2 Data/restraints/parameters 7566/0/457 Goodness-of-fit on F.sup.2 1.038 Final R indices [I > 2 (I)] R.sub.1 = 0.0308, wR.sub.2 = 0.0767 R indices (all data) R.sub.1 = 0.0331, wR.sub.2 = 0.0779 Extinction coefficient n/a Largest diff. peak and hole 1.311 and 0.786e.sup..sup.3
and

[0103] Single crystals of Pd(1-MeNAP)Br-.sup.tBuBrettPhos were grown by slow diffusion of n-hexane into a saturated solution of the complex in toluene. A crystal was taken up in perfluorinated oil and mounted onto a fiber loop on a Rigaku Oxford diffraction XtaLAB SuperNova diffractometer equipped with an Atlas CCD detector. The crystal was kept at 110.00(10) K during data collection. The obtained diffraction data was analyzed using CrysAlisPro software package. Using Olex2, the structure was solved with the ShelXT structure solution program using Intrinsic Phasing and refined with the ShelXL refinement package using Least Squares minimization (O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, H. Puschmann, J. Appl. Crystallogr. 2009, 42, 339-341; G. M. Sheldrick, Acta Crystallogr. Sect. Found. Adv. 2015, 71, 3-8; G. M. Sheldrick, Acta Crystallogr. Sect. C Struct. Chem. 2015, 71, 3-8; P. Van Der Sluis, A. L. Spek, Acta Crystallogr A Found Crystallogr 1990, 46, 194-201).

[0104] Crystal data and structure refinement for Pd(1-MeNAP)Br-.sup.tBuBrettPhos complex.

TABLE-US-00002 Identification code xub2255_auto_a.cif Empirical formula C33.60 H46.40 Br0.8 O1.60 P0.80 Pd0.80 Formula weight 649.73 Temperature 110(2) K Wavelength 1.54184 (Cu K) Crystal system monoclinic Space group P 21/c (no. 14) Unit cell dimensions a = 13.5515(2) = 90 b = 12.38630(10) = 97.4060(10) c = 22.8312(3) = 90 Volume 3800.31(8) .sup.3 Z 5 Density (calculated) 1.419 g/cm.sup.3 Absorption coefficient 5.821 mm.sup.1 F(000) 1688 Crystal size 0.240 0.204 0.131 mm.sup.3 Theta range for data collection 3.289 to 77.056 Index ranges 16 <= h <= 17, 15 <= k <= 6, 27 <= l <= 28 Reflections collected 27573 Independent reflections 7616 [R.sub.int = 0.0425, R.sub.sigma = 0.0370] Completeness to theta = 67.684 100% Absorption correction multi-scan Max. and min. transmission 1.00000 and 0.55798 Refinement method full-matrix least-squares on F.sup.2 Data/restraints/parameters 7616/0/438 Goodness-of-fit on F.sup.2 1.043 Final R indices [I > 2 (I)] R.sub.1 = 0.0298, wR.sub.2 = 0.0747 R indices (all data) R.sub.1 = 0.0326, wR.sub.2 = 0.0763 Extinction coefficient n/a Largest diff. peak and hole 0.651 and 0.802e.sup..sup.3

VI. Results on Hydrazine Coupling of Aryl Chloride

TABLE-US-00003 [00013] [00014] [00015] [00016] [00017] [00018] [00019] [00020] [00021] Ratio Entry Catalyst 2a [N.sub.2H.sub.4] (1a/2a) 3a [%] 3b [%] 3c [%] 1 Pd[P(o-tolyl).sub.3].sub.2/JosiPhos N.sub.2H.sub.4H.sub.2O 1:1 1 <1 <1 2 [Pd(cinnamyl)Cl].sub.2/MorDalPhos 14 3 5 3 [BrettPhos-Pd-G1] 18 2 8 4 Pd(OAc).sub.2/.sup.tBuBrettPhos <1 <1 <1 5 Pd.sub.2dba.sub.3/.sup.tBuBrettPhos 14 <1 32 6 [Pd(allyl)Cl].sub.2/.sup.tBuBrettPhos 3 <1 4 7 [Pd(cinnamyl)Cl].sub.2/.sup.tBuBrettPhos 13 <1 9 8 [Pd(1-MeNAP)Br].sub.2/.sup.tBuBrettPhos 14 <1 16 9 [.sup.tBuBrettPhos-Pd-G3] 66 <1 <1 10 [.sup.tBuBrettPhos-Pd-G6 Br] 84 <1 2 11 [AdBrettPhos-Pd-G6 Br] 51 <1 2 12 [Pd(1-MeNAP)(.sup.tBuBrettPhos)Br] 77 <1 2 13.sup.b [.sup.tBuBrettPhos-Pd-G3] [N.sub.2H.sub.5][OTf] 1:2 87 <1 <1 14.sup.b [.sup.tBuBrettPhos-Pd-G6 Br] 89 <1 4 15.sup.b [Pd(1-MeNAP)(.sup.tBuBrettPhos)Br] 98 <1 <1 Conditions: 1.0 mmol 1a, 1.0 mol% [Pd], 1.0 mol% ligand, 1.5 equiv. KOH, 1.5 mL dioxane, 25 C., 16 h. .sup.19F NMR yields with 1,4-difluorobenzene as internal standard. .sup.a[Pd]/ligand = 1:1.5 .sup.b4.5 equiv. KOH, 3 mL dioxane

Additional Screening Results

TABLE-US-00004 [00022] entry [N.sub.2H.sub.4] 11a [%] 11b [%] 11c [%] 1 N.sub.2H.sub.4H.sub.2O 95 <1 <1 2.sup.b [N.sub.2H.sub.5][OAc] 82 3 3.sup.b [N.sub.2H.sub.5][Cl] 95 <1 4.sup.b [N.sub.2H.sub.5][Br] 34 5.sup.b [N.sub.2H.sub.5] 93 1/2[SO.sub.4] 6.sup.b [N.sub.2H.sub.5][OTf] 96 7.sup.bc [N.sub.2H.sub.5][OTf] 98 .sup.aConditions: 1.0 mmol 10a, 2.0 equiv. [N.sub.2H.sub.4], 1.0 mol% [Pd(1-MeNAP)(.sup.tBuBrettPhos)Br], 3.0 equiv. KOH, 1.5 mL Dioxane, 25 C., 16 h. .sup.b4.5 equiv. KOH. .sup.c3 mL Dioxane. Yields determined by .sup.19F NMR using 1,4-difluorobenzene as internal standard.