WO2018106337A1

WO2018106337A1 - Mono-ligated palladium catalyts, their synthesis and use in suzuki coupling

Info

Publication number: WO2018106337A1
Application number: PCT/US2017/055737
Authority: WO
Inventors: Chunming Zhang; Kelli A. OGAWA; Siyu TU; James W. Ringer; Christopher W. Derstine
Original assignee: Dow Global Technologies LLC
Current assignee: Dow Global Technologies LLC
Priority date: 2016-12-06
Filing date: 2017-10-09
Publication date: 2018-06-14
Anticipated expiration: 2019-06-06

Abstract

The present invention is certain mono-ligated palladium catalysts that are easy to synthesize and are effective in Suzuki coupling reactions. These catalysts are characterized by an aromatic ring with a substituent group having an oxygen atom adjacent the aromatic ring and either an oxygen or nitrogen atom associated with the palladium atom.

Description

MONO-LIGATED PALLADIUM CATALYSTS, THEIR SYNTHESIS

AND USE IN SUZUKI COUPLING

FIELD OF THE INVENTION

[001] This invention relates generally to palladium catalysts and their method of manufacture.

INTRODUCTION

[002] Transition metal (e.g. palladium, nickel, or platinum) catalyzed reactions of aryl halide (iodide, bromide, chloride), and aryl pseudohalides (e. g. triflate, tosylate, mesylate, fluorosulfnate) with various substrates is a general method employed for the formation of C- C, C-N, C-0 bonds, which plays an important role in synthesis of fine chemicals, agricultural and pharmaceutical products, and advanced materials. The activity of transition metal catalysts is greatly influenced by the structural features and the number of associated ligand to the metal. Mono-ligated Pd(0) catalysts, bearing one bulk and electron-rich ligand, havd been demonstrated to be effective. Mono-ligated Pd(0) catalyst have been generated in situ from mono-ligated palladium (II) precatalysts, such as biphenyl palladacycle precatalyst described in prior art WO2013/184198 Al by Buchwald, and mono-ligated allylpalladium (II) complex described in prior art WO2011161451 Al by Colacot. See also Chen et. al, Tri(l-adamantyl)phosphine: Expanding the Boundary of Electron-Releasing Character Available to Oroganophosphorous Compounds, J. Am. Chem. Soc. 2016, 138, 6392-6395.

SUMMARY OF INVENTION

[003] The present inventors have discovered mono-ligated palladium catalysts that are easy to synthesize and are effective in Suzuki coupling reactions.

[004] Thus, according to one aspect, the invention is a composition comprising a compound of formula I

Formula I

wherein X is an anion,

L is a ligand, Y is R₅ wherein R5 is H, alkyl, aryl, or Y is OR₆ where R₆ is alkyl or aryl, or Y is NR7R8 wherein R7, Rs are each independently, H, alkyl, aryl; and

Z is O (oxygen), or NR9 wherein R9 is H, alkyl or aryl; and

Ri -R4 are each independently, H, alkyl, aryl, alkoxy, aryloxy; Ri and R2, R2 and R3, or R3 and R₄ could form a cycle.

[005] A method comprising making the compound of formula I comprising reacting formula III in a solvent with a Pd(II) source and an acid (HX) at a temperature in the range of 20 °C to 100 °C and then reacting Formula II with two ligands, L, at 0 °C to 100 °C in a

Formula III Formula II Formula I

[006] A method comprising reacting an aryl halide or pseudohalide with an organoboron compound in the presence of compound of Formula I.

Detailed Description

[007] For the Precatalysts of Formula I, preferably Ri - R₄ are selected from hydrogen, alkyl, and alkyloxy, where the alkyl and alkyloxy, preferably have from 1 to 20, more preferably 1 to 10, and most preferably 1-6 carbon atoms.

[008] In certain embodiments, the precatalyst has the formula 1-1 (An embodiment of Formula I, wherein Y = R5 , R5 is H, alkyl or aryl, preferably of 1 to 20, more preferably 1 to 10, and most preferably 1-6 carbon carbon atoms, Z = O, and Ri - R₄ are as defined above and X and L are as defined herein :

Formula 1-1 [009] In certain embodiments, the precatalyst has the formula 1-2 (An embodiment of Formula I, wherein Y = R₅ , R₅ is H, alkyl or aryl, preferably of 1 to 20, more preferably 1 to 10, and most preferably 1-6 carbon carbon atoms, Z = NR9 wherein R9 is H, alkyl, aryl, and Ri - R₄ are as defined above and X and L are as defined herein):

Formula 1-2

[0010] In certain embodiments, the precatalyst has the formula 1-3 (An embodiment of Formula I, wherein Y = OR₆ , R₆ is alkyl or aryl, preferably of 1 to 20, more preferably 1 to 10, and most preferably 1-6 carbon carbon atoms, Z = O, and Ri - R₄ are as defined above and X and L are as defined herein):

Formula 1-3

[0011] In certain embodiments, the precatalyst has the formula 1-4 (An embodiment of Formula I, wherein Y = OR₆ , R₆ is alkyl or aryl, preferably of 1 to 20, more preferably 1 to 10, and most preferably 1-6 carbon carbon atoms, Z = NR9 wherein R9 is H, alkyl, aryl, and Ri - R₄ are as defined above and X and L are as defined herein):

Formula 1-4

[0012] In certain embodiments, the precatalyst has the formula 1-5 (An embodiment of Formula I, wherein Y = NR7R8 where R7, Rs are each independently, H, alkyl, aryl, Z = O, and Ri - R₄ are as defined above and X and L are as defined herein):

Formula 1-5

[0013] In certain embodiments, the precatalyst has the formula 1-6 (An embodiment of Formula I, wherein Y = NR₇Rs where R₇, Rs are each independently, H, alkyl, aryl, Z = wherein R9 is H, alkyl, aryl, and Ri - R₄ are as defined above and X and L are as defined herein)

Formula 1-6

[0014] In certain embodiments, the precatalyst has the formula 1-7 (An embodiment of Formula I and 1-5, wherein Ri, R2, R₄ are H and Y = NR₇Rs, Z = O, and R3, R₇, Rs are as defined above and X and L are as defined herein):

Formula 1-7

[0015] In certain embodiments, the precatalyst has the formulae 1-8, 1-9, and 1-10 (An embodiments of Formula 1, 1-5 and 1-7 where Ri, R2, R* are H and R3 is as shown, Me = methyl, Y = NR₇Rs, Z = O, and R₇, Rs are as defined above and X and L are as defined herein):

Formula 1-8 Formula 1-9 Formula 1-10

[0016] In certain embodiments, the precatalyst has Formulae I-l 1, 1-12 or 1-13 (subspecies of Formulae 1-8, 1-9 and 1-10 where R₇ and Rs are Me, and X and L are as defined herein):

-5-

The Ligand and Anion

[0019] The precatalyst of this invention can contain any of a variety of known ligands. Among the preferred ligands are trialkylphosphine, triarylphosphine, dialkylarylphosphine, alkyldiarylphosphine, bis(phosphine), phosphoramide, or N-heterocyclic carbene.

The ligands may be selected from the group consisting of triphenylphosphine (PI13P), tri-t- butylphosphine(P(t-Bu)3), tricyclohexylphosphine (P(Cy)3) , tri(o-tolyl)phosphine( P(o- tol)₃), (+)-2,2'-Bis(diphenylphosphino)- 1 , 1 '-binaphthalene((+)-BINAP), 1,1'-

XantPhos

-7-

-8-

where Me is methyl, i-Pr is isopropyl, Cy is cyclohexyl, tBu is t-butyl, Ad is adamantyl, Xi is N or CH, R is alkyl, cycloalkyl or aryl of 1-20, preferably 1-10, more preferably 1-6 carbon atoms.

R^x is alkyl (such as butyl, adamantyl (Ad), benzyl, aryl

N-heterocyclic carbene, selected from imidazoline-2-ylidenes of the formula

or protonated salts thereof (which generate imidazoline-2-ylidenes in the presence of a base), wherein Ar is an aryl, R' and R", each are independently, hydrogen, halo, alkyl, or aryl. R' and R" are structures

Mes IPr

[0020] The anion X may be any anion but is preferably selected from group consisting of halide, alkylcarboxylate, boron tetrafluoride, tetraarylborates (such as B(C6Hs)4^~, and (B[3,5-(CF3)2C6H3]4)^"), alkylsulfonate, haloalkylsulfonate, and arylsulfonate. According to one preferred embodiment, the anion is a halide selected from fluoride, chloride, bromide or iodide. According to another preferred embodiment, X is alkylcarboxylate, and the alkyl is substituted or unsubstituted alkyl of 1 to 12 carbon atoms. Suitable substituents include halides (fluoro, chloro) and alkoxyl, aryloxyl, cyano, nitro, carbonyl. X may be acetate. X may be a haloalkylcarboxylate such as triflouroacetate (TFA) or trichloroacetate.

[0021] According to another embodiment X is alkylsulfonate, cycloalkyl or arylsulfonate, and the alkyl is a substituted or unsubstituted alkyl of 1 to 4 carbon atoms and the aryl may be a substituted or unsubstitued aryl of preferably 6 to 12 carbon atoms. X may be methylsulfonate, ethylsulfonate, methylphenylsulfonate or p-toluenesulfonate (TsO ). Suitable substituents include halides and alkoxyl, aryloxyl,cyano, nitro, carbonyl. X may be fluoroalkylsulfonate, such as trifluoromethylsulfonate (TfO ), nonafluorobutane sulfonate (NfO-).

Method of Making Precatalysts

[0022] In certain emodiments, the invention relates to a method of making any one of the aforementioned precatalysts, according to Scheme 1 from a palladacycle dimer of Formula

II

Formula II Formula I

Scheme 1

[0023] Preferably the above reaction is run in a polar aprotic solvent such as

tetrahydrofuran (THF) or methylene chloride (CH2CI2). Conditions for the reaction may be in the range of 0 °C to about 40 °C. The reaction should be allowed to run until substantially complete which may occur in the range of 30 minutes to 20 hours. It is preferable to perform the reactions under an inert atmosphere using a gas such as nitrogen or argon.

[0024] The dimers of Formula II may be obtained from any known source or may be made accordi

Formula III Formula II

Scheme 2 wherein the substrate of Formula III is obtained from a commercial source or prepared by known methods; X, Ri - R5, and Y are defined above. The Pd(II) source may be any known suitable source but is preferably palladium acetate (Pd(OAc)2). The solvent may be a non- polar or a polar aprotic solvent. Preferred solvents are toluene, methylene chloride, THF, or 1,4-dioxane. The reaction in scheme 2 takes place at 20 °C to about 100 °C. The reaction is typically complete after about 30 minutes to 20 hours.

Methods/Application of the Invention Suzuki Coupling

[0025] This invention also relates to the application of any one of the aforementioned precatalysts in Suzuki-Miyaura cross-coupling reactions of Scheme 3: precatalyst

R₁₀— X-l + Ri i- Βί - *~ Rl O^— Rl 1 base

solvent

organoboron tepmerature

Scheme 3

wherein,

the precatalyst is any one of the aforementioned precatalysts;

Rio is aryl, heteroaryl, alkyl, or alkenyl

Xi is I, Br, CI, or sulfonate (such as triflate, nonflate, tosylate, mesylate,

fluorosulfonate);

Rii is aryl, alkenyl, or alkyl, preferably of from 1 to 20, more preferably 1 to 10, and most preferably 1-6 carbon atoms ;

is a boron functional group, which is preferably selected from a group consisting of boronic acid, boronic ester (e.g. boronic acid binacol ester (BPin)), potasium trifluoroborate (-BF3K), N-methyliminodiacetic acid boronate (BMIDA), etc.

[0026] An embodiment of this invention provides a process which comprises mixing, in a liquid medium, i) at least one base; ii) at least one aryl halide or aryl pseudohalide (as defined below) in which all substituents are other than boron functionalized groups, wherein the aryl halide has, directly bonded to the aromatic ring(s), at least one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom, wherein aryl pseudohalide has, directly bonded to the aromatic ring(s), at least one pseudohalide group selected from sulfonates consisting of triflate (OTf), tosylate (OTs), nonflate, mesylate (OMs), and fluorosulfonate (SO2F); iii) at least one organoboron compound selected from arylboronic acid, arylboronic ester, aryltrifluoroborate, aryl-9- BBN (9-BBN refers to 9-borabicyclo[3.3.1]nonane), aryl-BMIDA, alkylboronic acid, alkylboronic ester, alkyl-9-BBN in which all substituents are other than chlorine atoms, bromine atoms, iodine atoms, or pseudohalide groups; iv) at least one of the aforementioned precatalysts, or in situ generated one of the aforementioned precatalysts via mixing of any one of aforementioned dimers and any one of the aforementioned ligands.

[0027] The liquid medium for the processes in this invention can include any of a wide range of solvents, and mixtures of solvents are also usable. The types of solvents that can be used include hydrocarbons, ethers, amides, ketones, alcohols, nitriles (acetonitrile), dimethyl sulfoxide, and water. Polar solvents are preferred. Ethers that may be used include, for example, 1 ,4-dioxane, tetrahydrofuran, glyme, diglyme. [0028] A large variety of bases are suitable for the processes in this invention. Generally, these are inorganic bases. Alkali metal salts are a preferred group of inorganic bases. Examples of suitable alkali metal salts include, but are not limited to, sodium acetate, sodium bicarbonate, sodium carbonate, sodium tert-butoxide, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium phosphate, potassium hydroxide, potassium tert-botoxide, cesium bicarbonate, and cesium carbonate. Alkali metal salts of carboxylic acid anions (e.g., acetate) are also suitable for use as an inorganic base in this invention. Amines (e.g. triethylamine, pyridine) are also suitable for use as a base in this invention. Choice(s) of base will vary with the particular system of aryl halide or pseudohalide and organoboron compound involved.

[0029] The aryl halide or pseudohalide has at least one halogen atom directly bonded to the aromatic ring(s) selected from a chlorine atom, a bromine atom, and a iodine atom, or at least one pseudohalide group. The term "pseudohalide group" includes such groups as arylsulfonate (e.g., p-toluenesulfonate (tosylate)), alkylsulfonate (e.g., methanesulfonate, OMs; trifluoromethanesulfonate (triflate)), and fluorosulfonate. The aryl moiety for the aryl halide or pseudohalide can be homocyclic or heterocyclic. Examples of suitable homocyclic aryl moieties include, but are not limited to benzene, naphthalene, anthracene,

phenanthrene, pyrene, biphenyl, fluorine and indene. Heterocyclic aryl moieties that can be used include, for example, furan, thiophene, oxathiolane, nitrogen-containing heterocycles, such as pyridine, indole, and isoxazole, and the like.

[0030] The organoboron compond in this invention is selected from aryl organoboron compounds, alkenyl organoboron compounds, and alkyl organoboron compounds. Suitable aryl organoboron compounds include arylboronic acid, arylboronic ester, aryl-BMIDA, aryltrifluoroborate, the aryl moieties are homocyclic or heteroyclic. Corresponding alkenyl and alkyl boron compounds may also be used in this invention.

[0031] Suitable reaction temperature ranges are from 0 - 200 °C, preferably 20 - 80 °C.

[0032] An embodiment of this invention is the Suzuki coupling of aryl halide/pesudohalide and aryl boron compound to generate biaryl compounds, illustrated in Scheme 3a

Precatalyst

Ar X Ar-|— B; base

1 + Ar-Ar-i

solvent

temaperature

Scheme 3 a wherein, Ar, Ari are each, independently, aryl groups (homocyclic or heterocyclic). The other components and reaction conditions are as discussed above.

[0033] The second embodiment of this invention is the Suzuki coupling of aryl

halides/pseudohalides and alkyl boron compounds, illustrated in Scheme 3b

Precatalyst

+ ^R-- — £ Ar-R₁₂

temaperature

Scheme 3b

Wherein, Ar is aryl groups (homocyclic or heterocyclic), R12 is an alkyl group, which can be non-cyclic or cyclic. The other components and reaction conditions are as discussed above.

[0034] The third embodiment of this invention is the Suzuki coupling of alkyl

halides/pseudohalides and alkyl boron compounds, illustrated in Scheme 3c

Precatalyst

R,3— X, ₊ K«-B? — - R₁₃-R₁₄

temaperature

Scheme 3c

wherein, R13 and Ri34are each, independently, alkyl groups or cycloalkyl groups. The other components and reaction conditions are as discussed above.

Examples

Example 1. Preparation of Di^-trifluoroacetoxy-bis(2-(dimethylcarbamoyl)oxy-4- methylphenyl-2C,0) dipalladium(II) (1)

1

In a 10-mL vial was added m-tolyl dimethylcarbamate (0.179 g, 1.0 mmol), methylene chloride (2 mL), and trifluoroacetic acid (114 mg, 1.0 mmol). The mixture was stirred for 5 min, then Pd(OAc)2 (225 mg, 1.0 mmol) was added. The mixture was stirred at ambient temperature overnight (20 h), resulting in a dark solution. The reaction mixture was concentrated under reduced pressure and the resulting oily residue was triturated with hexane (5 mL), followed by a mixture of t-butyl methyl ether (1 mL) and hexane (5 mL). The solid was filtered, rinsed with hexane, and dried in a vacuum oven to give the desired product (1), 0.18 g (45%), as a brown powder. Ή-ΝΜίΙ (400 HMz/DMSO-d6) δ 7.18 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.70 (s, 1H), 3.23 (s, 3 H), 2.97 (s, 3H), 2.24 (s, 3H).

Example 2. Trifluoroacetoxy-(2-(dimethylcarbamoyl)oxy-4-methylphenyl-2C,0)(tri-t- butylphosphine)dipalladium (II) (2

In a 10 mL flask was added the palladacycle dimer 1 (0.180 g, 0.453 mmol of monomer) and degassed THF (3 mL) and stirred at ambient temperature to form a brown solution, then 1.0 M t-Bu3P in toluene (0.46 mL, 0.46 mmol) was added. The mixture was stirred at ambient temperature under nitrogen atmosphere for 2 h, and was then concentrated under reduced pressure to give a brown oil. The oil was triturated with hexane (3 mL) to give a yellow solid. The solid was filtered, rinsed with hexane, and dried to give the desired product (2), 0.236 g (87%). ^!H-NMR (400 HMz?CDCl₃) δ 7.24 (m, 1H), 6.69 (d, J = 8.0 Hz, 1H), 6.61 (s, 1H), 3.23 (s, 3 H), 3.06 (s, 3H), 2.24 (s, 3H), 1.54 (d, J = 12.8 Hz, 27H). Example 3: The Suzuki Coupling reactions of 4-bromotoluene or 4-chlorotoluene and phenylboronic Acid

Entry XI Precatalyst yield³

1» Br 2 88%

2 CI 2 58%

3 CI Pd(OAc)₂/t-Bu₃P (1:1) 0%

¹ estimated by H-NMR; The reaction was complete in 20 min

General procedure: A palladium precatalyst (3 mol%) and phenylboronic acid (140.0 mg, 1.1 mmol, 1.1 equiv.) were added to a 25 mL tube flask under nitrogen. Then, a solution of 4-halotoluene (1.0 mmol) and octadecanol (internal standard, 0.50 mmol, 0.50 equiv) in ethanol (5 mL, degassed) was added, followed by addition of a solution of cesium carbonate (CS2CO3, 717 mg, 2.2 mmol, 2.2 equiv.) in water (1 mL, degassed). The tube was then heated and stirred at 60 °C for 1 h. A sample of the reaction mixture (~ 0.05 mL) was taken and analyzed by ^-NMR (in CD Ch) to determine yields.

Claims

WHAT IS CLAIMED IS :

1. A composition comprising a compound of Formula I

Formula I

wherein X is an anion,

L is a ligand,

Y is R₅ wherein R5 is H, alkyl, aryl, or Y is OR₆ where R₆ is alkyl or aryl, or Y is NR7R8 wherein R7, Rs are each independently, H, alkyl, aryl; and

Z is O (oxygen), or NR9 wherein R9 is H, alkyl or aryl; and

Ri -R4 are each independently, H, alkyl, aryl, alkoxy, aryloxy; Ri and R2, R2 and R3, or R3 and R4 could form a cycle.

2. The composition according to claim 1 wherein Y is NR₇Rs, R7, Rs are each

independently, H, alkyl, aryl, Z = O.

3. The composition according to claim 1 and 2, wherein Y is NR7R8, R7, Rs are each

independently, H, alkyl of 1 to 20 carbon atoms, or R7, Rs combine to form a cycle group.

4. The composition according to claims 1-3 wherein R7 and Rs are methyl.

5. The composition according to any one of claims 1-4 wherein Ri, R2, R3, R4 are

independently, alkyl, alkoxyl, of 1 to 20 carbon atoms, or H, provided at least one of Ri, R2, R3, R4 is alkyl or alkoxyl

6. The composition according to claim 5 wherein Ri, R2, and R4 are H and R3 is methyl or methoxy

7. The composition according to any one of claims 1-4 wherein RI, R2, R3, R4 are H.

8. The composition according to any one of claim 1-7 wherein L is selected from

trialkylphosphine, dialkylarylphosphine, alkyldiarylphosphine, and N-heterocylic carbene

9. The composition according to any one of claims 1-9, wherein X is selected from the group consisting of boron tetrafluoride, tetraarylborates; hexafluoroantimonate, phosphorus tetrafluoride, phosphorus hexafluoride, alkylsulfonate, haloalkylsulfonate, arylsulfonate, perchlorate, bis(alkylsulfonyl)amide, bis(fluoroalkylsulfonyl)amide, bis(arylsulfonyl)amide, (fluoroalkylsulfonyl)(fluoroalkylcarbonyl)amide, nitrate, nitrite, sulfate, hydrogensulfate, alkylsulfate, aryl sulfate, carbonate, carboxylate, phosphate, hydrogen phosphate, dihydrogen phosphate, phosphinate, and hypochlorite.

10. A process for making the compound of any one of claims 1-10 comprising the reaction of Formula III in a solvent with a Pd(II) source and an acid, HX, at a temperature in the range of 0 °C to 100 °C

Formula III Formula II wherein X is an anion,

Y is R₅ wherein R₅ is H, alkyl, aryl, or Y is OR₆ where R₆ is alkyl or aryl, or Y is NR₇Rs wherein R₇, Rs are each independently, H, alkyl, aryl; and

Z is O (oxygen), or NR9 wherein R9 is H, alkyl or aryl; and

Ri -R4 are each independently, H, alkyl, aryl, alkoxy, aryloxy; Ri and R2, R2 and R3, or

R3 and R₄ could form a cycle; and

R5-R9 are each independently, H, alkyl, aryl;

and then reacting Formula II with ligand, L, at 0 ⁰ to 40 °C in a polar aprotic solvent to form the compound of any one of claims 1-10

11. A process comprising reacting an aryl or alkyl halide or aryl or alkyl or sulfonate with an organoboron compound in an organic solvent/water system in the presence of base and a composition of any of claims 1-12.

12. The process of claim 13 wherein an aryl halide or aryl sulfonate is reacted with the organoboron compound which has the formula Rn-^"~B,¾ where ^B^ is a boron functional group, selected from a group consisting of boronic acid, boronic ester, potasium trifluoroborate, and N-methyliminodiacetic acid boronate, and Rn is an aryl group.