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Catalytic C–H Arylation of Unactivated C–H Bonds by Silylium Ion-Promoted C(sp)–F Bond Activation 2
Hendrik F. T. Klare ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.7b02658 • Publication Date (Web): 06 Sep 2017 Downloaded from http://pubs.acs.org on September 7, 2017
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Catalytic C–H Arylation of Unactivated C–H Bonds by Silylium Ion-Promoted C(sp2)–F Bond Activation Hendrik F. T. Klare* Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 115, 10623 Berlin, Germany ABSTRACT: Silylium ions facilitate the catalytic direct cross-coupling of aryl fluorides with simple arenes and alkanes. This C–H arylation approach is initiated by silylium ion-mediated fluoride abstraction, followed by Friedel–Crafts or C–H insertion reactions of the resulting phenyl cation equivalents. An ortho-silyl group in the fluoroarene substrate is the key for selective intermolecular transformations, stabilizing the aryl cation intermediate and serving as an internal silylium ion precursor.
KEYWORDS: carbocations, C–F bond activation, C–H bond activation, cross-coupling, main-group catalysis, silylium ions
The catalytic functionalization of C–F bonds has emerged as an attractive tool to directly access valuable chemical building blocks from fluorinated molecules.1 Considerable progress in this area relies on the transition-metal-mediated cross-coupling of aryl fluorides with prefunctionalized coupling partners for the formation of C(sp2)–C(sp2) bonds.2 Conversely, strong main-group Lewis acids such as silylium ions (R3Si+) have been shown to effect heterolytic fluoride abstraction in saturated fluorocarbons, thereby generating stabilized carbenium ions that can undergo classical inter- or intramolecular Friedel–Crafts reactions in the presence of sufficiently nucleophilic arenes (Scheme 1, top).3–6 While this process is thermodynamically favored, the reverse approach, i.e. using aryl fluorides as electrophile source, is hampered by both the intrinsic instability of the aryl cation and the inertness of the hydrocarbon C–H bond (Scheme 1, bottom). Hence, such catalytic C–H arylation reactions were not known until the recent pioneering contributions from the Siegel7–9 and Nelson groups.10 Scheme 1. Complementary Strategies for C(sp2)– C(sp3) Bond Formation by Silylium IonPromoted C–F Bond Activationa
aThe weakly coordinating counteranion is omitted for clarity.
In a seminal report, a team led by Reed, Baldridge and Siegel discovered that silylium ions are indeed capable of heterolytic C(sp2)–F bond activation when paired with Reed’s robust and extremely weakly coordinating carborane anion [CHB11Cl11]–.7 Fluoride abstraction from fluorobenzene (1) by solvent-stabilized triethylsilylium ion 2 is observed at 80 °C, resulting in the formation of fluorosilane 3 and a highly unstable phenyl cation intermediate that is stabilized by regioisomeric adduct formation with the carborane anion (Scheme 2, top). The thus-generated zwitterionic phenyl chloronium salts 4a and 4b are inert in solution but serve as phenylating agents in the presence of stronger nucleophiles such as pyridine, Et3N, or Ph3P. The use of the intramolecularly arene-stabilized terphenylsilylium ion 5 allows for fluoride abstraction even at room temperature (Scheme 2, bottom). The C(sp2)–F bond cleavage is facilitated by concomitant nucleophilic attack of the adjacent xylyl ring. Deprotonation of the intermediate Wheland complex by a sterically hindered base such as phosphine 6 yields the Friedel–Crafts arylation product 7 along with fluorosilane 8 and phosphonium salt 9. Scheme 2. Heterolytic C(sp2)–F Bond Activation by Silylium Ions
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Providing practicable access to aryl cation equivalents, this previously unprecedented reactivity profile of silylium ions opened the door to novel synthetically useful C–H arylation protocols. Based on their early results, Siegel and co-workers developed an intramolecular Friedel–Crafts-type coupling of fluoroarenes, affording various polycyclic aromatic hydrocarbons and graphene frameworks.8 As illustrated by the synthesis of fluoranthene (10 → 13, Scheme 3), these C(sp2)–H arylation reactions are initiated by fluoride abstraction from 10 with catalytic amounts of silylium ion 11 (10 → 17+). The high kinetic barrier of this step is likely to be lowered by simultaneous intramolecular nucleophilic attack of the proximal aryl moiety (17+ → 18+), thereby generating Wheland complex 18+ without unfavorable formation of free aryl cation 17+ via a dissociative mechanism analogous to classical SN1-type reactions. To close the catalytic cycle, the group of Siegel has elaborated a cleverly devised strategy: Instead of simply neutralizing the Wheland intermediate by addition of a base, they made use of the Brønsted acidity of 18+ to regenerate a silylium ion by protodesilylation of dimesityldimethylsilane (12). In this thermodynamically driven process, intermolecular proton transfer from 18+ to stoichiometrically added silane 12 affords product 13 (18+ → 13) with concomitant formation of the more stable β-silicon-stabilized Wheland complex 19+ (12 → 19+) that, in turn, rearomatizes to mesitylene (14) with release of a silylium ion due to the greater bond strength of the C–H over the C–Si bond (19+ → 14 + 20+). The newly formed silylium ion 20+ then acts as the fluoride-abstracting reagent in the following catalytic turnover. Scheme 3. Intramolecular Friedel–Crafts-Type C(sp2)–H Arylation by Silylium Ion-Promoted C(sp2)–F Bond Activation
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The tremendous synthetic potential of this methodology was recently demonstrated by Bonifazi and coworkers in the first straightforward synthesis of borazino-doped coronene derivative 22, involving six (!) C(sp2)–C(sp2) ring closure steps at the same time (Scheme 4).11 Scheme 4. Application of Siegel’s Protocol in Materials Science
Notably, Siegel and co-workers also observed competing C(sp2)–C(sp3) bond formation when the biaryl fluoride is decorated with an aliphatic ortho-substituent (e.g., 23 → 24 versus 23 → 25 in Scheme 5).9 The chemoselectivity is generally poor, but exclusive C(sp2)– C(sp3) coupling is seen in cases where the Friedel–Crafts reaction would result in the energetically unfavored formation of a strained four-membered ring. Theoretical calculations and a control experiments using a deuterium-labeled probe support a mechanism including a C(sp3)–H bond insertion of the incipient aryl cation. Such intramolecular cyclizations under formal C–H bond activation find precedence in the Mascarelli reaction for the synthesis of fluorenes by thermolysis of diazonium salts.12,13
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Scheme 5. Competing Intramolecular C(sp2)–H and C(sp3)–H Arylation
From a synthetic point of view, it would be particularly attractive to implement the cross-coupling of aryl fluorides and hydrocarbons in selective intermolecular processes. While the application of Siegel’s intramolecular protocol failed, Nelson and co-workers now successfully addressed this unmet challenge by taking advantage of the well-established β-silicon effect: The use of an orthosilyl group in the fluoroarene substrate not only allows for the intermolecular Friedel–Crafts-type C–H arylation of unactivated arenes (26 + 27 → 28, Scheme 6) but also for the direct cross-coupling of β-silylated aryl fluorides 26 with simple alkanes (26 + 30 → 32, Scheme 6).10 The ortho-silyl group is beneficial in several respects: β-silyl stabilization of the positive charge in aryl cation intermediate 33+ lowers the barrier for fluoride abstraction (26 and 36+ → 33+, Scheme 6) and is expected to tame the electrophilicity of 33+.14 After insertion of the incipient aryl cation into the C–H bond of hydrocarbon 30 (33+ + 30 → 34+) and subsequent 1,2hydride shift (34+ → 35+), the resulting β-siliconstabilized Wheland complex 35+ seeks rearomatization to yield product 32 with release of trimethylsilylium ion 36+ (35+ → 32 + 36+), thereby closing the catalytic cycle. Hence, the ortho-silyl group can be considered as both a traceless directing group and an internal silylium ion precursor that maintains catalytic turnover. Scheme 6. Intermolecular C(sp2)–H and C(sp3)– H Arylation by Silylium Ion-Promoted C(sp2)–F Bond Activation
The exceptional efficiency of this novel C–H arylation strategy was finally highlighted in a rare example of direct methane functionalization (Scheme 7).10 With only 3.6% initiator loading of silylium ion 2, the arylation of methane with β-silylated fluoronaphthalene 37 succeeded in 32% isolated yield under comparatively mild reaction conditions (60 °C and 35 bar methane pressure).15 Scheme 7. C–H Arylation of Methane by Silylium Ion-Promoted C(sp2)–F Bond Activation
To recap, the exceptionally high Lewis acidity and fluoride affinity of silylium ions paved the way to novel C– H arylation protocols based on heterolytic C(sp2)–F bond activation. A chemical twist of intermolecular (18+ + 12 → 20+, Scheme 3) to intramolecular protodesilylation (34+ → 36+, Scheme 6) for silylium ion regeneration led from intra- (10 → 13, Scheme 3) to intermolecular C–H arylation reactions (26 + 27 → 28 and 26 + 30 → 32, Scheme 6). For the latter scenario, the key to success was the presence of an ortho-silyl group in the fluoroarene substrate that stabilizes the putative aryl cation interme-
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diate and also serves as an internal silylium ion precursor. The direct cross-coupling of aryl fluorides and simple hydrocarbons by means of a tandem C–F/C–H bond activation process is an unprecedented transformation that has not been achieved under transition-metal catalysis. Owing to their non-oxidative nature, these metalfree coupling reactions provide access to molecules, which are difficult to prepare using traditional synthetic approaches. In particular, the recent advances offer new avenues for the synthesis of π-conjugated polycyclic arenes, which are important motifs in materials science (cf. Scheme 4). Moreover, this conceptually novel C–H arylation methodology allows for the selective functionalization of C–F bonds in the presence of weaker C–X bonds (X = Cl, Br, and I), thereby complementing classical transition metal-mediated cross-coupling reactions. However, some synthetic drawbacks remain: Aside from the necessary installation of the silyl group in the substrate for intermolecular processes, these reactions suffer from intrinsic limitations associated with the highly Lewis-acidic reaction conditions, such as limited functionalgroup compatibility, selectivity issues and undesired protodesilylation of the starting materials. Nevertheless, catalytic C–H arylations based on silylium ion-promoted C(sp2)–F bond activation represent another milestone in the emerging area of main-group catalysis. Further achievements can be expected. Stay tuned!
AUTHOR INFORMATION Corresponding Author *E-mail:
[email protected].
ORCID Hendrik F. T. Klare: 0000-0003-3748-6609.
Funding Sources Financial support by the Technische Universität Berlin is gratefully acknowledged.
Notes
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(4) For general reviews of silylium ion chemistry, see: (a) Müller, T. In Structure and Bonding; Scheschkewitz, D., Ed.; Springer: Berlin, 2014; Vol. 155, pp 107–162. (b) Müller, T. In Science of Synthesis: Knowledge Updates 2013/3; Oestreich, M., Ed.; Thieme: Stuttgart, 2013; pp 1–42. (c) Schulz, A.; Villinger, A. Angew. Chem., Int. Ed. 2012, 51, 4526–4528. (d) Klare, H. F. T.; Oestreich, M. Dalton Trans. 2010, 39, 9176– 9184. (5) For silylium ion-promoted C(sp3)–F bond activation, see: (a) Scott, V. J.; Çelenligil-Çetin, R.; Ozerov, O. V. J. Am. Chem. Soc. 2005, 127, 2852–2853. (b) Panisch, R.; Bolte, M.; Müller, T. J. Am. Chem. Soc. 2006, 128, 9676–9682. (c) Douvris, C.; Stoyanov, E. S.; Tham, F. S.; Reed, C. A. Chem. Commun. 2007, 1145–1147. (d) Douvris, C.; Ozerov, O. V. Science 2008, 321, 1188–1190. (e) Douvris, C.; Nagaraja, C. M.; Chen, C.-H.; Foxman, B. M.; Ozerov, O. V. J. Am. Chem. Soc. 2010, 132, 4946–4953. (6) For intermolecular Friedel–Crafts alkylations by silylium ion-promoted C(sp3)–F bond activation, see: Lühmann, N.; Panisch, R.; Müller, T. Appl. Organomet. Chem. 2010, 24, 533–537. (7) Duttwyler, S.; Douvris, C.; Fackler, N. L. P.; Tham, F. S.; Reed, C. A.; Baldridge, K. K.; Siegel, J. S. Angew. Chem., Int. Ed. 2010, 49, 7519–7522. (8) Allemann, O.; Duttwyler, S.; Romanato, P.; Baldridge, K. K.; Siegel, J. S. Science 2011, 332, 574–577. (9) Allemann, O.; Baldridge, K. K.; Siegel, J. S. Org. Chem. Front. 2015, 2, 1018–1021. (10) Shao, B.; Bagdasarian, A. L.; Popov, S.; Nelson, H. M. Science 2017, 355, 1403–1407. (11) Dosso, J.; Tasseroul, J.; Fasano, F.; Marinelli, D.; Biot, N.; Fermi, A.; Bonifazi, D. Angew. Chem., Int. Ed. 2017, 56, 4483–4487. (12) Mascarelli, L. Gazz. Chim. Ital. 1936, 66, 843–850. (13) For an example of a photoinduced intramolecular C–H insertion reaction of an aryl fluoride, see: Fasani, E.; Mella, M.; Caccia, D.; Fagnoni, M.; Albini, A. Chem. Commun. 1997, 1329–1330. (14) Laali, K. K.; Rasul, G.; Prakash, G. K. S.; Olah, G. A. J. Org. Chem. 2002, 67, 2913–2918. (15) For other C–H functionalizations of methane, see: (a) Hashiguchi, B. G.; Konnick, M. M.; Bischof, S. M.; Gustafson, S. J.; Devarajan, D.; Gunsalus, N.; Ess, D. H.; Periana, R. A. Science 2014, 343, 1232–1237. (b) Cook, A. K.; Schimler, S. D.; Matzger, A. J.; Sanford, M. S. Science 2016, 351, 1421–1424. (c) Smith, K. T.; Berritt, S.; González-Moreiras, M.; Ahn, S.; Smith III, M. R.; Baik, M.-H.; Mindiola, D. J. Science 2016, 351, 1424–1427.
The author declares no competing financial interest.
ACKNOWLEDGMENT The author thanks Professor Dr. Martin Oestreich (TU Berlin) for the fruitful teamwork and his generous support.
REFERENCES (1) For an authoritative review of C–F bond activation, see: Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119–2183. (2) For reviews of C–F bond functionalization by transitionmetal-mediated C–F bond activation, see: (a) Ahrens, T.; Kohlmann, J.; Ahrens, M.; Braun, T. Chem. Rev. 2015, 115, 931–972. (b) Keyes, L.; Love J. A. In C–H and C–X Bond Functionalization; Ribas X., Ed.; RSC Publishing: Cambridge, 2013; pp 159–192. (3) For reviews of C–F bond activation by silylium ions, see: (a) Stahl, T.; Klare, H. F. T.; Oestreich, M. ACS Catal. 2013, 3, 1578–1587. (b) Takikawa, H. J. Synth. Org. Chem., Jpn. 2012, 70, 395–396. (c) Meier, G.; Braun, T. Angew. Chem., Int. Ed. 2009, 48, 1546–1548.
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