Synlett 2021; 32(05): 511-516
DOI: 10.1055/s-0040-1707266
cluster
The Power of Transition Metals: An Unending Well-Spring of New Reactivity

Identification of a Surprising Boronic Acid Homocoupling Process in Suzuki–Miyaura Cross-Coupling Reactions Utilizing a Hindered Fluorinated Arene

Samantha L. Gargaro
a  Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, VA 23284-3028, USA
,
Bre'Shon Dunson
a  Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, VA 23284-3028, USA
b  Thomas Jefferson High School, 4100 W Grace Street, Richmond, VA 23230, USA
,
a  Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, VA 23284-3028, USA
› Author Affiliations
Startup funding was provided by the Virginia Commonwealth University and the Bill and Melinda Gates Foundation (The Medicines for All Institute, grant number OPP1176590)


Dedicated to Professor Barry Trost in honor of his 80th birthday.

Abstract

The Suzuki–Miyaura cross-coupling reaction of 2-bromo-1,3-bis(trifluoromethyl)benzene with arylboronic acids was evaluated and determined to suffer from the formation of large amounts of boronic acid homocoupling products in conjunction with dehalogenation. Homocoupling product formation in this process likely occurs through a rare protonolysis/second transmetalation event rather than by the well-established mechanism requiring the involvement of O2. The scope of this boronic acid homocoupling reaction was investigated and shown to predominate with electron-deficient arylboronic acids. Finally, a good yield of cross-coupling products could be obtained by employing dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (SPhos) as the ligand.

Supporting Information



Publication History

Received: 16 July 2020

Accepted after revision: 03 August 2020

Publication Date:
27 August 2020 (online)

© 2020. Thieme. All rights reserved

Georg Thieme Verlag KG
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  • References and Notes


    • For reviews, see:
    • 1a Suzuki A. J. Organomet. Chem. 1999; 576: 147
    • 1b Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457
    • 1c Alonso F, Beletskaya IP, Yus M. Tetrahedron 2008; 64: 3047
    • 1d Miyaura N. Top. Curr. Chem. 2002; 219: 11
    • 2a Bellina F, Carpita A, Rossi R. Synthesis 2004; 2419
    • 2b Christmann U, Vilar R. Angew. Chem. Int. Ed. 2005; 44: 366
    • 2c Johansson Seechurn CC. C, Kitching MO, Colacot TJ, Snieckus V. Angew. Chem. Int. Ed. 2012; 51: 5062
    • 2d Lundgren RJ, Stradiotto M. Chem. Eur. J. 2012; 18: 9758
    • 2e Miura M. Angew. Chem. Int. Ed. 2004; 43: 2201
    • 2f Martin R, Buchwald SL. Acc. Chem. Res. 2008; 41: 1461
    • 2g DeAngelis AJ, Gildner PG, Chow R, Colacot TJ. J. Org. Chem. 2015; 80: 6794
    • 2h Kinzel T, Zhang Y, Buchwald SL. J. Am. Chem. Soc. 2010; 132: 14073
    • 2i Yang Y, Oldenhuis NJ, Buchwald SL. Angew. Chem. Int. Ed. 2013; 52: 615
    • 2j Bruno NC, Tudge MT, Buchwald SL. Chem. Sci. 2013; 4: 916
    • 2k Li H, Johansson Seechurn CC. C, Colacot TJ. ACS Catal. 2012; 2: 1147
    • 2l Gildner PG, Colacot TJ. Organometallics 2015; 34: 5497
    • 4a Cox PA, Reid M, Leach AG, Campbell AD, King EJ, Lloyd-Jones GC. J. Am. Chem. Soc. 2017; 139: 13156
    • 4b Cox PA, Leach AG, Campbell AD, Lloyd-Jones GC. J. Am. Chem. Soc. 2016; 138: 9145
  • 5 Lennox AJ. J, Lloyd-Jones GC. Isr. J. Chem. 2010; 50: 664
    • 6a Adamo C, Amatore C, Ciofini I, Jutand A, Lakmini H. J. Am. Chem. Soc. 2006; 128: 6829
    • 6b Moreno-Mañas M, Pérez M, Pleixats R. J. Org. Chem. 1996; 61: 2346
    • 6c Aramendia MA, Lafont F. J. Org. Chem. 1999; 64: 3592
    • 6d Yoshida H, Yamaryo Y, Ohshita J, Kunai A. Tetrahedron Lett. 2003; 44: 1541
    • 6e Wong MS, Zhang XL. Tetrahedron Lett. 2001; 42: 4087
    • 7a Dolbier WR. J. Fluorine Chem. 2005; 126: 157
    • 7b Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
    • 7c O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
    • 7d Purser S, Moor PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
    • 7e Yale HL. J. Med. Pharm. Chem. 1959; 1: 121
    • 8a Liu Q, Lan Y, Liu J, Li G, Wu Y.-D, Lei A. J. Am. Chem. Soc. 2009; 131: 10201
    • 8b Wang J, Meng G, Xie K, Li L, Sun H, Huang Z. ACS Catal. 2017; 7: 7421
  • 9 Walker SD, Barder TE, Martinelli JR, Buchwald SL. Angew. Chem. Int. Ed. 2004; 43: 1871
  • 10 Biphenyl-4,4′-dicarbaldehyde (14a); Typical HC Procedure A crimp-cap vial equipped with magnetic stirrer bar was charged with (dppf)PdCl2 ·CH2Cl2 (8.2 mg, 0.010 mmol), (4-formylphenyl)boronic acid (2a; 97.9 mg, 0.653 mmol), Na2CO3 (69.2 mg, 0.653 mmol), and 2-bromo-1,3-bis(trifluoromethyl)benzene (6; 95.7 mg, 0.327 mmol). The vial was sealed with a crimp-cap septum and filled with Ar by using three vacuum–purge cycles. Degassed (Ar sparge) 1,4-dioxane (0.70 mL) and H2O (0.25 mL) were added, and the vial was immersed in an oil bath at 90 °C for 2 h, then cooled to r.t. H2O was added and the mixture was extracted with CH2Cl2 (2 × 4 mL). The combined organics were mixed with PhCF3 (60.0 μL, 0.488 mmol) as an added standard, and an aliquot was diluted in CDCl3 for quantitative 19F NMR spectroscopy. The organics were then dried (Na2SO4) and concentrated in vacuo. Purification by flash chromatography [silica gel, hexanes–EtOAc (0–25%)] gave a white solid; yield: 53.2 mg (77%); mp 141–143 °C; Rf = 0.26 (25% EtOAc–hexanes). 1H NMR (600 MHz, CDCl3): δ = 10.09 (s, 2 H), 8.00 (d, J = 8.0 Hz, 4 H), 7.80 (d, J = 8.0 Hz, 4 H). 13C NMR (CDCl3, 150 MHz): δ = 191.7, 145.5, 135.9, 130.4, 128.0. HRMS (DART): m/z [M + H]+ calcd for C14H11O2: 211.0759; found: 211.0788.
  • 11 O’Duill ML, Engle KM. Synthesis 2018; 50: 4699
    • 12a Carrow BP, Hartwig JF. J. Am. Chem. Soc. 2011; 133: 2116
    • 12b Thomas AA, Denmark SE. Science 2016; 352: 329
    • 12c Thomas AA, Wang H, Zahrt AF, Denmark SE. J. Am. Chem. Soc. 2017; 139: 3805
    • 12d Thomas AA, Zahrt AF, Delaney CP, Denmark SE. J. Am. Chem. Soc. 2018; 140: 4401
    • 12e Lennox AJ. J, Lloyd-Jones GC. Angew. Chem. Int. Ed. 2013; 52: 7362
    • 12f Amatore C, Jutand A, Le Duc G. Chem. Eur. J. 2011; 17: 2492
    • 12g Ortuño MA, Lledós A, Maseras F, Ujaque G. ChemCatChem 2014; 6: 3132
    • 12h Sicre C, Braga AA. C, Maseras F, Cid MM. Tetrahedron 2008; 64: 7437
    • 12i Braga AA. C, Morgon NH, Ujaque G, Maseras F. J. Am. Chem. Soc. 2005; 127: 9298
    • 12j Braga AA. C, Morgon NH, Ujaque G, Lledós A, Maseras F. J. Organomet. Chem. 2006; 691: 4459
    • 12k Braga AA, Ujaque G, Maseras F. Organometallics 2006; 25: 3647
    • 12l Miyaura N. J. Organomet. Chem. 2002; 653: 54
  • 13 The results obtained are also consistent with the formation of HC product 14a from 21 through a bimetallic-catalyst-exchange mechanism where aryl–aryl exchange between two molecules of 18 occurs to generate 21 along with a symmetrical Pd complex bearing two 2,6-bis(trifluoromethyl)phenyl fragments that would need to undergo protonolysis to form 9 and reenter the catalytic cycle. For an example of bimetallic exchange, see: Wang D., Izawa Y., Stahl S. S.; J. Am. Chem. Soc.; 2014, 136: 9914

    • Other strategies to facilitate reductive elimination using electron-deficient fluorinated styrenes as additives have been reported. It is possible that coordination of electron-deficient arene 9 to the Pd-intermediates involved in these processes might play a role in the observed reaction outcomes. For examples, see:
    • 14a Giovannini R, Knochel P. J. Am. Chem. Soc. 1998; 120: 11186
    • 14b Giovannini R, Stüdemann T, Devasagayaraj A, Dussin G, Knochel P. J. Org. Chem. 1999; 64: 3544
    • 14c Giovannini R, Stüdemann T, Dussin G, Knochel P. Angew. Chem. Int. Ed. 1998; 37: 2387
  • 15 See the Supporting Information.
  • 16 2′,6′-Bis(trifluoromethyl)biphenyl-4-carbaldehyde (13a): Typical CC Procedure A crimp-cap vial equipped with magnetic stirrer bar was charged with Pd(OAc)2 (2.2 mg, 0.010 mmol), SPhos (8.3 mg, 0.020 mmol), (4-formylphenyl)boronic acid (2a; 97.9 mg, 0.653 mmol), Na2CO3 (69.2 mg, 0.653 mmol), and 2-bromo-1,3-bis(trifluoromethyl)benzene (6; 95.7 mg, 0.327 mmol). The vial was sealed with a crimp-cap septum and filled with Ar by using three vacuum–purge cycles. Degassed (Ar sparge) 1,4-dioxane (0.70 mL) and H2O (0.25 mL) were added, and the vial was immersed in an oil bath at 90 °C for 2 h, then cooled to r.t. H2O was added, and the mixture was extracted with CH2Cl2 (2 × 4 mL). The combined organics were mixed with PhCF3 (60.0 μL, 0.488 mmol) as an added standard, and an aliquot was diluted in CDCl3 for quantitative 19F NMR spectroscopy. The organics were then dried (Na2SO4) and concentrated in vacuo. Purification by flash chromatography [silica gel, hexanes–EtOAc (0–25%)] gave a yellow oil; yield: 84.6 mg (85%); Rf = 0.59 (25% EtOAc–hexanes). 1H NMR (600 MHz, CDCl3): δ = 10.09 (s, 1 H), 7.99 (d, J = 8.0 Hz, 2 H), 7.91 (d, J = 8.0 Hz, 2 H), 7.68 (t, J = 8.0 Hz, 1 H), 7.45 (d, J = 8.0 Hz, 2 H). 13C NMR (150 MHz, CDCl3): δ = 191.8, 140.3, 138.7, 136.1, 130.9 (q, J = 30.0 Hz), 130.8, 129.4 (q, J = 5.0 Hz), 128.5, 128.2, 123.1 (q, J = 275.0 Hz). 19F NMR (565 MHz, CDCl3): δ = –57.5. HRMS (DART): m/z [M + H]+ calcd for C15H9F6O: 319.0558; found: 319.0578.
    • 17a Patel ND, Sieber JD, Tcyrulnikov S, Simmons BJ, Rivalti D, Duvvuri K, Zhang Y, Gao DA, Fandrick KR, Haddad N, Lao KS, Mangunuru HP. R, Biswas S, Qu B, Grinberg N, Pennino S, Lee H, Song JJ, Gupton B F, Garg NK, Kozlowski MC, Senanayake CH. ACS Catal. 2018;  8: 10190
    • 17b Yin JJ, Buchwald SL. J. Am. Chem. Soc. 2000; 122: 12051
    • 17c Shen X, Jones GO, Watson DA, Bhayana B, Buchwald SL. J. Am. Chem. Soc. 2010; 132: 11278
    • 17d Cammidge AN, Crépy KV. L. Chem. Commun. 2000; 1723
    • 17e Cammidge AN, Crépy KV. L. Tetrahedron 2004; 60: 4377
    • 17f Bermejo A, Ros A, Fernández R, Lassaletta JM. J. Am. Chem. Soc. 2008; 130: 15798
    • 17g Uozumi Y, Matsuura T, Arakawa T, Yamada YM. Angew. Chem. Int. Ed. 2009; 48: 2708
    • 17h Jensen JF, Johannsen M. Org. Lett. 2003; 5: 3025
    • 17i Genov M, Almorín A, Espinet P. Chem. Eur. J. 2006; 12: 9346
    • 17j Mešková M, Putala M. Tetrahedron: Asymmetry 2013; 24: 894