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WO2017112576A1 - Procédés de couplage de suzuki sans base externe - Google Patents

Procédés de couplage de suzuki sans base externe Download PDF

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Publication number
WO2017112576A1
WO2017112576A1 PCT/US2016/067474 US2016067474W WO2017112576A1 WO 2017112576 A1 WO2017112576 A1 WO 2017112576A1 US 2016067474 W US2016067474 W US 2016067474W WO 2017112576 A1 WO2017112576 A1 WO 2017112576A1
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WO
WIPO (PCT)
Prior art keywords
palladium
aromatic compound
bis
nickel
reaction mixture
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2016/067474
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English (en)
Inventor
Jason S. FISK
Carol GELBAUM
Bruce S. Holden
Arvind JAGANATHAN
Zhao Li
Charles Liotta
Pamela Pollet
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Georgia Tech Research Institute
Georgia Tech Research Corp
Dow Global Technologies LLC
Original Assignee
Georgia Tech Research Institute
Georgia Tech Research Corp
Dow Global Technologies LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Georgia Tech Research Institute, Georgia Tech Research Corp, Dow Global Technologies LLC filed Critical Georgia Tech Research Institute
Publication of WO2017112576A1 publication Critical patent/WO2017112576A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/04—Substitution

Definitions

  • a Suzuki-style reaction scheme using one or more heteroaryl molecules is desired.
  • a Suzuki-style reaction scheme performed without the addition of an external base is desired where the initial pH of the reaction mixture is less than 11 and the final pH is less than 7.
  • the present disclosure describes a method of coupling a first aromatic compound to a second aromatic compound, the method comprising: (a) preparing a reaction mixture comprising the first aromatic compound, the second aromatic compound, a catalyst and water; the reaction mixture does not contain an external base, the reaction mixture having an initial pH of from 11 to 1; the catalyst having at least one group 10 atom; the first aromatic compound having a halogen, triflate or sulfonate substituent; the second aromatic compound having a boron-containing substituent; wherein, at least one of the first aromatic compound or the second aromatic compound includes one or more heteroatom; and (b) reacting the first aromatic compound and the second aromatic compound in the reaction mixture, the reaction mixture having a final pH of less than 7 following reaction of the first aromatic compound and the second aromatic compound.
  • numeric ranges for instance "from 2 to 10,” are inclusive of the numbers defining the range (e.g., 2 and 10).
  • molecular weight refers to the number average molecular weight as measured in conventional manner.
  • Alkyl as used in this specification, whether alone or as part of another group (e.g., in dialkylamino), encompasses straight, branched and cyclic chain aliphatic groups having the indicated number of carbon atoms. If no number is indicated (e.g., aryl-alkyl-), then 1- 12 alkyl carbons are contemplated.
  • Preferred alkyl groups include, without limitation, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, cyclopentyl, hexyl, cyclohexyl and tert-octyl.
  • heteroalkyl refers to an alkyl group as defined above with one or more heteroatoms (nitrogen, oxygen, sulfur, phosphorus) replacing one or more carbon atoms within the radical, for example, an ether or a thioether.
  • Aromatic compound refers to a ring system having 4n+2 pi electrons where n is an integer greater than or equal to zero.
  • Preferred aryls include, without limitation, phenyl, naphthyl, anthracenyl, and fluorenyl. Unless otherwise indicated, the aryl group is optionally substituted with 1 or more substituents that are compatible with the syntheses described herein. Such substituents include, but are not limited to, sulfonate groups, boron- containing groups, alkyl groups, nitro groups, halogens, cyano groups, carboxylic acids, esters, amides, C2-C 8 alkene, amines and other aromatic groups. Other substituents are known in the art. Unless otherwise indicated, the foregoing substituent groups are not themselves further substituted.
  • Heteroaryl refers to any functional group or substituent derived from an aromatic ring and containing at least one heteroatom within the ring and selected from nitrogen, oxygen, and sulfur.
  • the heteroaryl group is a five or six-membered ring.
  • the heteroaryl ring may be fused or otherwise attached to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings or heterocycloalkyl rings.
  • heteroaryl groups include, without limitation, pyridine, pyrimidine, pyridazine, pyrrole, triazine, imidazole, triazole, furan, thiophene, oxazole, thiazole.
  • the heteroaryl group may be optionally substituted with one or more substituents that are compatible with the syntheses described herein.
  • substituents include, but are not limited to, fluorosulfonate groups, boron-containing groups, Ci-C 8 alkyl groups, nitro groups, halogens, cyano groups, carboxylic acids, esters, amides, C2-C8 alkenes, amines and other aromatic groups.
  • substituents are known in the art. Unless otherwise indicated, the foregoing substituent groups are not themselves further substituted.
  • an "external base” refers to a base that is added to the reaction scheme separate from the reactants.
  • the reaction mixture described herein does not include an external base.
  • the reaction mixture described herein has an initial pH, as measured after all of the reactants have been combined. In one instance, the initial pH is from 11 to 1. More preferably, the initial pH is from 10 to 4.
  • Heteroatom refers to an atom that is not carbon or hydrogen. Examples of suitable heteroatoms include N, O, S, P, CI, Br, or I.
  • Equation 1 A 1 refers to a first aromatic compound
  • a 2 refers to a second aromatic compound
  • X refers to a halogen, triflate or fluorosulfonate
  • B Y refers to a boron- containing substituent.
  • suitable substituents include, but are not limited to, C1-C10 alkyl, C1-C10 amino, and C1-C10 heteroalkyl. At least one of A 1 or A 2 includes a heteroatom.
  • the heteroatom of at least one of A 1 or A 2 is a member of an aromatic ring. In one instance, the heteroatom of at least one of A 1 or A 2 is a member of a substituent to one of the aromatic rings. The heteroatom of at least one of A 1 or A 2 is separate from any heteroatoms present in X or B Y . In one instance the heteroatom is nitrogen.
  • the result of the reactions shown in Equation 1 is the formation of a new carbon-carbon bond between the first aromatic compound and the second aromatic compound, thereby coupling the first aromatic compound to the second aromatic compound. Unexpectedly, it has been found that the reaction of Equation 1 may be performed without adding external base with a reaction mixture having an initial pH of less than 11 and a final pH of less than 7.
  • the second aromatic compound includes a boron-containing substituent as identified in Equation 1 as B Y .
  • the boron-containing substituent is of the formula -BF 3 M "1" where M + is an alkali metal cation or an unsubstituted ammonium ion. Unsubstituted ammonium ion refers to NH 4 + .
  • the boron of the boron-containing substituent has one or more alkyl substituent, for example, 9- borabicyclo[3.3.1]nonane.
  • the boron-containing substituent is of the formula shown in Equation 2.
  • the catalyst includes at least one group 10 atom.
  • the group 10 atoms include nickel, palladium and platinum.
  • the catalyst is generated in-situ from a palladium precatalyst, the palladium precatalyst is selected from the group consisting of: Palladium(II) acetate, Palladium(II) chloride, Dichlorobis(acetonitrile)palladium(II),
  • the catalyst is generated in-situ from a nickel precatalyst
  • the nickel precatalyst is selected from the group consisting of: nickel(II) acetate, nickel(II) chloride, Bis(triphenylphosphine)nickel(II) dichloride, Bis(tricyclohexylphosphine)nickel(II) dichloride, [1,1 '-Bis(diphenylphosphino)ferrocene]dichloronickel(II) , Dichloro [ 1 ,2- bis(diethylphosphino)ethane]nickel(II), Chloro(l-naphthyl)bis(triphenylphosphine) nickel(II), l,3-Bis(2,6-diisopropylphenyl)imidazolium chloride, Bis(l,5- cyclooctadiene)nickel(O), Nickel(II) acetate, nickel
  • pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI) type catalysts are used, for example, [1,3-Bis(2,6- Diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) dichloride, and (1,3- Bis(2,6-diisopropylphenyl)imidazolidene) ( 3-chloropyridyl) palladium(II) dichloride.
  • nickel precatalysts include, but are not limited to, nickel(II) acetate, nickel(II) chloride, Bis(triphenylphosphine)nickel(II) dichloride,
  • the halogen of the first aromatic compound is bromine and the reaction mixture does not include a ligand. In one instance, the halogen of the first aromatic compound is chlorine and the reaction mixture further comprises a ligand. In one instance, the reaction mixture further comprises a ligand. In one instance, the reaction mixture does not contain a ligand.
  • the present disclosure describes a method of coupling a first aromatic compound to a second aromatic compound, the method comprising: (a) preparing a reaction mixture comprising the first aromatic compound, the second aromatic compound, a catalyst and water; the reaction mixture having an initial pH of from 11 to 1 ; the catalyst having at least one group 10 atom; the first aromatic compound having a halogen, triflate or sulfonate substituent; the second aromatic compound having a boron-containing substituent; wherein, at least one of the first aromatic compound or the second aromatic compound includes one or more heteroatom; and (b) reacting the first aromatic compound and the second aromatic compound in the reaction mixture, the reaction mixture having a final pH of less than 7 following reaction of the first aromatic compound and the second aromatic compound.
  • the present disclosure further describes a method of coupling a first aromatic compound to a second aromatic compound, the method comprising: (a) preparing a reaction mixture comprising the first aromatic compound, the second aromatic compound, a catalyst and water; the reaction mixture does not contain an external base, the reaction mixture having an initial pH of from 11 to 1; the catalyst having at least one group 10 atom; the first aromatic compound having a halogen, triflate or sulfonate substituent; the second aromatic compound having a boron-containing substituent; wherein, at least one of the first aromatic compound or the second aromatic compound includes one or more heteroatom; and (b) reacting the first aromatic compound and the second aromatic compound in the reaction mixture, the reaction mixture having a final pH following reaction of the first aromatic compound and the second aromatic compound, the final pH less than 7.
  • the reactions were biphasic with an aqueous phase and a solid phase.
  • the cooled reaction mixture was basified to pH > 12 using 30% NaOH aqueous solution, and then thoroughly extracted with ethyl acetate.
  • the combined organic phase was dried over anhydrous MgSC , filtered, and then concentrated in vacuo.
  • the crude product was analyzed by GC and ! ⁇ NMR, as provided in Table 1.
  • phenylboronic acid 1.341 g, 11 mmol, 1.1 equiv
  • K 3 PO 4 as specified in Table 2
  • Pd(OAc) 2 0.0449 g, 0.2 mmol, 0.02 equiv
  • H 2 0 25 mL, 1384 mmol
  • the initial and final pH values of the aqueous phase were measured before and after the heating was enabled when the temperature was stabilized at 25 - 27 °C, and listed in Table 2.
  • the cooled reaction mixture was basified to pH > 12 using 30% NaOH aqueous solution, and then was thoroughly extracted with organic solvent (chloroform for aliphatic amine-containing substrates and ethyl acetate for aminopyridine substrates).
  • organic solvent chloroform for aliphatic amine-containing substrates and ethyl acetate for aminopyridine substrates.
  • the combined organic phase was dried over anhydrous MgSC , filtered, and then concentrated in vacuo.
  • the crude product was analyzed by GC and ! ⁇ NMR, as provided in Table 5.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un procédé de couplage d'un premier composé aromatique à un second composé aromatique. Le procédé consiste: a) à préparer un mélange réactionnel comprenant le premier composé aromatique, le second composé aromatique, un catalyseur et de l'eau; le mélange réactionnel ne contient pas de base externe, le mélange réactionnel ayant un pH initial de 11 à 1; le catalyseur comportant au moins un atome du groupe 10; le premier composé aromatique comportant un substituant halogène, triflate ou sulfonate; le second composé aromatique comporte un substituant boré; et le premier composé aromatique et/ou le second composé aromatique comprennent un ou plusieurs hétéroatomes; et b) à mettre en réaction le premier composé aromatique et le second composé aromatique dans le mélange réactionnel, lequel présente un pH final après réaction du premier composé aromatique et du second composé aromatique.
PCT/US2016/067474 2015-12-21 2016-12-19 Procédés de couplage de suzuki sans base externe Ceased WO2017112576A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201562270296P 2015-12-21 2015-12-21
US62/270,296 2015-12-21
US201662427436P 2016-11-29 2016-11-29
US62/427,436 2016-11-29

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WO2017112576A1 true WO2017112576A1 (fr) 2017-06-29

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999028313A1 (fr) * 1996-12-05 1999-06-10 Merck & Co., Inc. Inhibiteurs de la farnesyl-proteine transferase
US20040063744A1 (en) * 2002-05-28 2004-04-01 Tao Wang Indole, azaindole and related heterocyclic 4-alkenyl piperidine amides
US20040224952A1 (en) * 2003-05-07 2004-11-11 Cowart Marlon D. Fused bicyclic-substituted amines as histamine-3 receptor ligands
WO2009110985A2 (fr) * 2008-02-29 2009-09-11 Renovis, Inc. Composés amides, compositions à base de ces composés et leurs utilisations
WO2011086125A1 (fr) * 2010-01-15 2011-07-21 N.V. Organon Derives de 1h-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999028313A1 (fr) * 1996-12-05 1999-06-10 Merck & Co., Inc. Inhibiteurs de la farnesyl-proteine transferase
US20040063744A1 (en) * 2002-05-28 2004-04-01 Tao Wang Indole, azaindole and related heterocyclic 4-alkenyl piperidine amides
US20040224952A1 (en) * 2003-05-07 2004-11-11 Cowart Marlon D. Fused bicyclic-substituted amines as histamine-3 receptor ligands
WO2009110985A2 (fr) * 2008-02-29 2009-09-11 Renovis, Inc. Composés amides, compositions à base de ces composés et leurs utilisations
WO2011086125A1 (fr) * 2010-01-15 2011-07-21 N.V. Organon Derives de 1h-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
AIICHIRO NAGAKI ET AL: "Flow synthesis of arylboronic esters bearing electrophilic functional groups and space integration with Suzuki-Miyaura coupling without intentionally added base", CHEMICAL COMMUNICATIONS - CHEMCOM., vol. 48, no. 91, 1 January 2012 (2012-01-01), pages 11211, XP055353094, ISSN: 1359-7345, DOI: 10.1039/c2cc36197c *
AIICHIRO NAGAKI ET AL: "Supporting Information Flow Synthesis of Arylboronic Esters Bearing Electrophlic Functional Groups and Space Integration with Suzuki- Miyaura Coupling Without Intentionally Added Base", ELECTRONIC SUPPLEMENTARY MATERIAL (ESI) FOR CHEMICAL COMMUNICATIONS, 1 January 2012 (2012-01-01), pages 1 - 18, XP055353095, Retrieved from the Internet <URL:http://www.rsc.org/suppdata/cc/c2/c2cc36197c/c2cc36197c.pdf> [retrieved on 20170309] *
ALASTAIR J. J. LENNOX ET AL: "Selection of boron reagents for Suzuki-Miyaura coupling", CHEMICAL SOCIETY REVIEWS., vol. 43, no. 1, 1 January 2014 (2014-01-01), GB, pages 412 - 443, XP055349575, ISSN: 0306-0012, DOI: 10.1039/C3CS60197H *
JAMES J. SAHN ET AL: "Expedient Synthesis of Norbenzomorphan Library via Multicomponent Assembly Process Coupled with Ring-Closing Reactions", ACS COMBINATORIAL SCIENCE, vol. 14, no. 9, 10 September 2012 (2012-09-10), US, pages 496 - 502, XP055313866, ISSN: 2156-8952, DOI: 10.1021/co300068a *
KOBAYASHI Y ET AL: "Scope and limitation of the nickel-catalyzed coupling reaction between lithium borates and mesylates", JOURNAL OF ORGANOMETALLIC CHEMISTRY, ELSEVIER-SEQUOIA S.A. LAUSANNE, CH, vol. 653, no. 1-2, 1 July 2002 (2002-07-01), pages 91 - 97, XP004361509, ISSN: 0022-328X, DOI: 10.1016/S0022-328X(02)01174-9 *
TOMOYUKI SAEKI ET AL: "Boron Trifluoride Induced Palladium-Catalyzed Cross-Coupling Reaction of 1-Aryltriazenes with Areneboronic Acids", ORGANIC LETTERS , 14(23), 6012-6015 CODEN: ORLEF7; ISSN: 1523-7052, vol. 6, no. 4, 1 February 2004 (2004-02-01), pages 617 - 619, XP055353093, ISSN: 1523-7060, DOI: 10.1021/ol036436b *
VITO GALLO ET AL: "Ionic Liquids as Reaction Media for Palladium-Catalysed Cross-Coupling of Aryldiazonium Tetrafluoroborates with Potassium Organotrifluoroborates", EUROPEAN JOURNAL OF INORGANIC CHEMISTRY - CHEMISCHE BERICHTE, vol. 2005, no. 3, 1 February 2005 (2005-02-01), DE, pages 582 - 588, XP055353072, ISSN: 1434-1948, DOI: 10.1002/ejic.200400637 *
ZHAO LI ET AL: "Aqueous Suzuki Coupling Reactions of Basic Nitrogen-Containing Substrates in the Absence of Added Base and Ligand: Observation of High Yields under Acidic Conditions", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 81, no. 18, 25 August 2016 (2016-08-25), pages 8520 - 8529, XP055349593, ISSN: 0022-3263, DOI: 10.1021/acs.joc.6b01683 *
ZHIMIN PENG ET AL: "Palladium-Catalyzed Suzuki Cross-Coupling of Arylhydrazines via C-N Bond Cleavage", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 79, no. 6, 21 March 2014 (2014-03-21), pages 2733 - 2738, XP055349590, ISSN: 0022-3263, DOI: 10.1021/jo500026g *

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