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. 2026 Sep 29. Online ahead of print. doi: 10.1039/d6qo01119e

A one carbon linchpin for Rh(iii)-catalyzed, C(sp3)-directed C–H annulation

Michael R Hollerbach a,†, Eleda V Plouch a,†, Samantha M Velazquez a, Simon B Blakey a,✉
PMCID: PMC13639656  PMID: 42840465

Abstract

We disclose a new platform for C(sp3)-directed C–H annulations to generate valuable heterocycles from readily available starting materials. A commercially available one carbon linchpin is leveraged to access alkyl boron species from simple anilines. Rhodium-catalyzed C(sp3) transmetallation from this key intermediate provides a C–Rh bond appropriately positioned for ortho-C–H activation, enabling formation of a C,C-rhodacycle. With the addition of a variety of alkyne coupling partners, diverse dihydroquinolines are synthesized.

We report a C(sp3)-directed C–H annulation using a one-carbon linchpin to form an alkyl boron substrate that undergoes Rh(iii)-catalyzed transmetallation, C–H activation, and alkyne annulation, enabling access to diverse dihydroquinolines.graphic file with name d6qo01119e-ga.webp

Introduction

C–H functionalization is a straightforward and effective method to generate complexity in organic molecules. The ubiquity of C–H bonds allows for a uniquely broad scope of potential transformations but also presents a challenge in selectivity due to similarity in the chemical environments of various C–H bonds in the substrate. One method to overcome this challenge is to utilize the coordination of a nearby functional group to position the metal close to the desired C–H bond. The majority of directing groups are heteroatom based, requiring appropriately positioned native functionality or the installation and removal of the directing group.1–4 A less-explored alternative to this paradigm is direct utilization of carbon atoms to position the metal. These directing groups then form the carbon skeleton of the products, providing access to novel C–C bond forming reactions and offering significant promise to expand the scope of directed C–H functionalization.

Carbon-directed C–H functionalization was pioneered by Baudoin,5–9 Knochel,10 Fagnou,11 Ohno,12 Kündig,13–15 Cramer,16,17 and others,18 who first accessed these directing C–M bonds via palladium-catalyzed oxidative addition from a C–X species (Fig. 1a). Subsequent activation of a nearby C–H bond generates a metallocycle, and reductive elimination furnishes the cyclic products. Satoh and Miura developed a carbon-directed C–H activation reaction utilizing transmetallation from an aryl boronic acid (Fig. 1b), and Ackermann and coworkers subsequently developed an electrochemical equivalent.19–21 In these rhodium-catalyzed reactions, one equivalent of alkyne is introduced through migratory insertion to position the metal appropriately for ortho C–H activation, generating a 5-membered metallocycle. Migratory insertion of a second equivalent of alkyne followed by reductive elimination gives the tetraphenylnaphthalene products. Currently, carbon-directed C–H annulation chemistry remains underdeveloped. Few examples of C(sp3)-directed annulations exist,22–24 and coupling partners are limited.

Fig. 1. Background and overview of this carbon-directed C–H functionalization.

Fig. 1

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Limited additional reports utilizing a boron species as a precursor for carbon-directed C–H annulation reactions are known,20,21,25–27 although others have used these materials in 1,4-metal migration reactions.28 Inspired by the work of Satoh, Miura, and Ackermann, we recognized the untapped potential for boron as a traceless transmetallation agent to enable carbon-directed C–H annulation reactions. Specifically, we envisioned that commercially available 1 could act as a linchpin reagent, readily introduced to heteroatom nucleophiles to install the alkyl boron,29 which can be used to affect a variety of annulations, yielding heterocyclic skeletons (Fig. 1c). Incorporation of a carbon directing group directly into the skeleton unlocks a new scope of reactivity. Herein, we demonstrate this platform in the context of a modular synthesis of dihydroquinolines from simple anilines and alkynes.

Results and discussion

We began our investigation into the annulation reaction by exploring the possibility of using Cp* ligated Co, Rh, and Ir complexes to catalyze the reaction under oxidative conditions (Table 1). After investigating the reaction parameters, we found that the reaction could be successfully conducted using 5 mol% [RhCp*Cl2]2 as the catalyst, with 20 mol% AgSbF6 employed as a halide scavenger under rigorously dry conditions in dioxane. We found that 2 equivalents of Cu(OAc)2 were necessary as the oxidant and that 1.2 equivalents of alkyne coupling partner was optimal. We noted that the addition of an acid additive to aid in proton abstraction during the proposed concerted metalation-deprotonation (CMD) step significantly improved yields, with benzoic acid derivatives leading to fewer side products and providing an opportunity for electronic tuning.30–32 We identified 4-CF3BzOH to be optimal and a 1 : 1 ratio of additive to rhodium to be necessary for higher yield. We found iridium and cobalt catalysts to be ineffective in this transformation. However, [RhCptBuCl2]2 and [RhInd*Cl2]2 both successfully catalyzed the reaction, albeit in diminished yields.

Table 1. Optimization of reaction for catalyst, additive, and oxidant.

graphic file with name d6qo01119e-u1.webp
Entry Deviation from std. cond. Yield of 4 a
1 None 76% (72%)b
2 [lrCp*Cl2]2 (5 mol%) as catalyst 0%
3 [CoCp*(CO)l2] (10 mol%) as catalyst 0%
4 [RhCptBuCl2]2 (5 mol%) as catalyst 38%
5 [Rhlnd*Cl2]2 (5 mol%) as catalyst 42%
6 AcOH in place of 4-CF3BzOH 46%
7 PivOH in place of 4-CF3BzOH 21%
8 BzOH in place of 4-CF3BzOH 35%
9 AgOAc in place of Cu(OAch)2 >5%
10 AgOBz in place of Cu(OAch)2 >5%
11 100 °C 52%
12 140 °C 40%
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a

Reactions were run on a 0.1 mmol scale. Yields were calculated by 19F NMR using α,α,α-trifluorotoluene as an internal standard.

b

Isolated yield.

During early optimization, we observed low yields along with the formation of quinoline byproduct 5 resulting from elimination of the tosyl group from 4. When the reaction was doped with 20 mol% of this byproduct, reactivity was completely inhibited, suggesting that the quinoline may be acting as a Lewis basic poison, coordinating with the rhodium and removing it from a productive catalytic cycle. Fortunately, our optimization efforts, and particularly the use of additive 4-CF3BzOH, minimized the formation of this byproduct.

With the optimized system in hand, we investigated the reactions of a variety of anilines and substituted arylalkynes. We first examined a series of para-substituted aniline derivatives (Fig. 2a, 6a–6h). These included a continuum of electron-donating to electron-withdrawing substituents, all of which were well-tolerated and generated the desired products in moderate to good yields (27–78%). No clear electronic trends were observed in the data. Notably, handles for further functionalization such as an aryl halide (6e, 59% yield), an olefin (6g, 53% yield), and an ester (6h, 63% yield) were well-tolerated.

Fig. 2. Scope of aniline and alkyne coupling partners. a Yields refer to the isolated product. Regioselectivity determined by 1H NMR. Reactions were run on a 0.2 mmol scale. b Enantioselectivity determined by HPLC using a chiral stationary phase.

Fig. 2

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Substituents at the meta-position gave products in moderate yields (7a–7d, 32–63%), potentially due to increased steric congestion. Again, both electron-donating and electron-withdrawing substituents were tolerated. Notably, the meta-substitutions bearing an alkyl group (7c and 7d; 32% and 54% yield) were highly regioselective at >20 : 1 rr for the less sterically encumbered product. However, meta-alkoxy substituents (7a and 7b; 57% and 63% yield) resulted in more moderate regioselectivities (1.1 : 1 and 1.7 : 1 respectively). Although it is possible that the reduced regioselectivity arises from the smaller size of the alkoxy substituents (A-values: CH3 = 1.8 kcal mol−1vs. CH3O = 0.60 kcal mol−1),33 we speculate that this observed mixture of products may be attributed to either a coordination effect, in which the oxygen atom may be coordinating with the Rh catalyst and guiding it to the more sterically congested site, or to the well-documented ortho-effect, in which the ortho-electronegative substituents increase the bond strength of M–C bonds.34,35 Reaction with a 3,4-dioxole-containing substrate produced 13 in 41% yield and 1.6 : 1 rr and favored the ortho-substituted product regioisomer.

In evaluating multi-substituted aryl rings, a 3,5-methoxy-substituted substrate gave 8 in a 39% yield, and 3,4-disubstituted substrates gave 9 and 10 in yields of 75% and 74%, both with excellent regioselectivities (>20 : 1 rr) favoring the less sterically congested product. Importantly, several heterocyclic amines were tolerated. A 4-aminopyridine derivative gave the annulated product 11 in a 50% yield, and structure 12, from the 3-aminopyridine derivative, was obtained in a 69% yield and 4 : 1 rr between the 2- and 4-positions, respectively. Finally, nosyl and mesyl groups on the nitrogen were both tolerated, giving the desired products 14 and 15 in 68% and 81% yield, respectively.

Next, we turned our attention to the effect of various alkynyl substituents on the reaction (Fig. 2b). An alkyne bearing one electron-rich aryl substituent and one electron-deficient aryl substituent reacted efficiently (16, 80% yield), but with limited regioselectivity (1.7 : 1). Alkynes that were substituted with one aryl group and one alkyl group reacted with good yields (17–23, 52–74% yield) and excellent regioselectivity; in all but one case, products in which the alkyl group was adjacent to the aromatic ring were observed in >20 : 1 rr. Cyclopropane 18 was synthesized in 71% yield with excellent regioselectivity (>20 : 1 rr). Use of a TIPS protected propargyl alcohol gave 19 in a 64% yield and >20 : 1 rr, and no degradation of enantiopurity was observed for secondary alcohol 20 (62% yield, >20 : 1 rr, 98% ee).

Alkynes containing a variety of heteroaryl substituents were also well-tolerated (21–25, 28–75% yield). Again, simple alkyl-heteroaryl disubstituted alkynes were incorporated with excellent regioselectivity (21–22, >20 : 1 rr). However, an alkyne substituted with a tBu group and a pyridine provided product 23 in a 1 : 1 ratio of regioisomers, likely due to the similarity in size between these two substituents compared to other alkyl–aryl alkynes. Products 24 and 25, obtained from alkynes bearing phenyl substituents and a pyridine and pyrrole respectively, were obtained in modest yields and selectivities (49% yield, 2.1 : 1 rr, and 28% yield, 1.7 : 1 rr). 3-(Phenylethynyl)pyridine was not a viable substrate in this reaction, as no product was observed (SI page 37). Additionally, terminal alkynes were not tolerated in this reaction.

In assessing both the practicality and applicability of this reaction, we have demonstrated that the reaction can be successfully scaled to 2.2 mmol, maintaining a similar yield and the high regioselectivity (67%; >20 : 1 rr) observed in the original 0.1 mmol reaction (Fig. 3a). We have highlighted the value of these products by performing several one-step transformations to access other heterocycles (Fig. 3b). The fully aromatized quinoline 27 was accessed from 4 in quantitative yield using potassium hydroxide in ethanol at 100 °C. Rhodium-catalyzed oxidation of 17 provided conversion to tosyl deprotected 2-quinolone 28 in 61% yield. Hydrogenation of 17 gave tetrahydroquinoline 30 in a 71% yield, and tosyl deprotection of 29via acridine radical reduction provided 30 in 73% yield.36

Fig. 3. Representative functionalization of products. a Standard conditions (std. cond.): 2 (2.2 mmol), 26 (1.2 equiv.), [RhCp*Cl2]2 (5 mol%), AgSbF6 (20 mol%), 4-CF3BzOH (10 mol%), Cu(OAc)2 (2 equiv.), dioxane (45 mL), 120 °C, 24 h. Yield refers to the isolated product.

Fig. 3

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To better understand the mechanism of this reaction, we performed several probing experiments. We investigated the reversibility of C–H activation by synthesizing deuterated analogues of our starting materials to study hydrogen incorporation at the position ortho to the amine. Under standard reaction conditions, we observed only 5% H/D exchange in product 32 (Fig. 4a). Increasing the loading of the benzoic acid resulted in greatly diminished yields, and notably did not lead to a measurable increase in deuterium incorporation. In a separate experiment, one equivalent of tAmOH was included as a proton source, and only 2% H/D exchange was observed (SI page 42). These experiments suggest the C–H activation is largely irreversible. In a competitive intermolecular kinetic isotope effect (KIE) experiment, we observed a KIE of kH/kD = 1.0, indicating that the C–H activation step is not turnover-limiting (Fig. 4b).37

Fig. 4. Mechanistic investigations and proposed mechanism. a Standard conditions: 31 (0.1 mmol), 3 (1.2 equiv.) [RhCp*Cl2]2 (5 mol%), AgSbF6 (20 mol%), 4-CF3BzOH (10 mol%), Cu(OAc)2 (2 equiv.), dioxane (2 mL), 120 °C, 24 h. Yield refers to the isolated product. b Standard conditions: 33 (0.05 mmol, 0.5 equiv.), 31 (0.05 mmol,0.5 equiv.), [RhCp*Cl2]2 (5 mol%), AgSbF6 (20 mol%), 4-CF3BzOH (10 mol%), Cu(OAc)2 (2 equiv.), dioxane (2 mL), 100 °C, 24 h.

Fig. 4

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Based on these findings and previous reports,19,38,39 we propose a plausible mechanism for this transformation (Fig. 4c). Initially, [RhCp*Cl2]2 is dehalogenated by AgSbF6. The resulting catalytic species I can engage the substrate and undergo transmetallation to form intermediate II. Subsequent carboxylate assisted CMD of the ortho C–H proton and alkyne coordination gives intermediate III as a 5-membered rhodacycle. Formal migratory insertion of the alkyne gives 7-membered C,C-rhodacycle intermediate IV, which undergoes reductive elimination, then oxidation with copper acetate to complete the catalytic cycle. To provide further evidence for this catalytic cycle, we attempted to isolate intermediates II or III; however, we were not successful.

Conclusions

In conclusion, we have developed a new platform for C(sp3)-directed C–H annulation reactions, presenting a novel method for the generation of dihydroquinolines using a convenient commercially available linchpin reagent. Exceptional regioselectivity is observed in many cases, and a diverse array of heterocyclic coupling partners is tolerated. The dihydroquinoline products are readily transformed into a variety of valuable motifs, highlighting this as a versatile new method for medicinal chemistry campaigns. Underpinning the methodology, we have demonstrated that, through efficient access to a traceless alkyl boron species, sp3 transmetallation is an effective route to access carbon-based directing groups capable of affecting novel annulation reactions. We anticipate further development of this novel strategy will open many opportunities for new carbon-directed C–H annulation reactions.

Author contributions

All authors have given approval to the final version of the manuscript. M. R. H and E. V. P. contributed equally and are listed in alphabetical order.

Conflicts of interest

There are no conflicts to declare.

Supplementary Material

QO-OLF-D6QO01119E-s001

Acknowledgments

This research was supported by the National Institutes of Health (GM136880). In addition, this material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. 1937971. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. NMR data were collected on instruments obtained with support from the National Science Foundation (CHE-1521620).

Data availability

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information: experimental procedures, characterization data, and figures including NMR spectra and HPLC traces. See DOI: https://doi.org/10.1039/d6qo01119e.

References

  1. Davies H. M. L. Morton D. Recent advances in C–H functionalization. J. Org. Chem. 2016;81:343–350. doi: 10.1021/acs.joc.5b02818. [DOI] [PubMed] [Google Scholar]
  2. Guillemard L. Kaplaneris N. Ackermann L. Johansson M. J. Late-stage C–H functionalization offers new opportunities in drug discovery. Nat. Rev. Chem. 2021;5:522–545. doi: 10.1038/s41570-021-00300-6. [DOI] [PubMed] [Google Scholar]
  3. Rej S. Ano Y. Chatani N. Bidentate directing groups: an efficient tool in C–H bond functionalization chemistry for the expedient construction of C–C bonds. Chem. Rev. 2020;120:1788–1887. doi: 10.1021/acs.chemrev.9b00495. [DOI] [PubMed] [Google Scholar]
  4. Sambiagio C. Schönbauer D. Blieck R. Dao-Huy T. Pototschnig G. Schaaf P. Wiesinger T. Zia M. F. Wencel-Delord J. Besset T. Maes B. U. W. Schnürch M. A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry. Chem. Soc. Rev. 2018;47:6603–6743. doi: 10.1039/C8CS00201K. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baudoin O. Herrbach A. Guéritte F. The Palladium-Catalyzed C–H Activation of Benzylic gem-Dialkyl Groups. Angew. Chem., Int. Ed. 2003;42:5736–5740. doi: 10.1002/anie.200352461. [DOI] [PubMed] [Google Scholar]
  6. Hitce J. Retailleau P. Baudoin O. Palladium-Catalyzed Intramolecular C(sp3)–H Functionalization: Catalyst Development and Synthetic Applications. Chem. – Eur. J. 2007;13:792–799. doi: 10.1002/chem.200600811. [DOI] [PubMed] [Google Scholar]
  7. Chaumontet M. Piccardi R. Audic N. Hitce J. Peglion J. L. Clot E. Baudoin O. Synthesis of benzocyclobutenes by palladium-catalyzed C–H activation of methyl groups: method and mechanistic study. J. Am. Chem. Soc. 2008;130:15157–15166. doi: 10.1021/ja805598s. [DOI] [PubMed] [Google Scholar]
  8. Yang L. Melot R. Neuburger M. Baudoin O. Palladium(0)-catalyzed asymmetric C(sp3)–H arylation using a chiral binol-derived phosphate and an achiral ligand. Chem. Sci. 2017;8:1344–1349. doi: 10.1039/C6SC04006C. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holstein P. M. Vogler M. Larini P. Pilet G. Clot E. Baudoin O. Efficient Pd0-Catalyzed Asymmetric Activation of Primary and Secondary C–H Bonds Enabled by Modular Binepine Ligands and Carbonate Bases. ACS Catal. 2015;5:4300–4308. doi: 10.1021/acscatal.5b00898. [DOI] [Google Scholar]
  10. Ren H. Knochel P. Chemoselective Benzylic C–H Activations for the Preparation of Condensed N–Heterocycles. Angew. Chem., Int. Ed. 2006;45:3462–3465. doi: 10.1002/anie.200600111. [DOI] [PubMed] [Google Scholar]
  11. Lafrance M. Gorelsky S. I. Fagnou K. High-yielding palladium-catalyzed intramolecular alkane arylation: reaction development and mechanistic studies. J. Am. Chem. Soc. 2007;129:14570–14571. doi: 10.1021/ja076588s. [DOI] [PubMed] [Google Scholar]
  12. Watanabe R. Oishi S. Fujii N. Ohno H. Palladium-Catalyzed sp3 C–H Activation of Simple Alkyl Groups: Direct Preparation of Indoline Derivatives from N-Alkyl-2-bromoanilines. Org. Lett. 2008;10:1759–1762. doi: 10.1021/ol800425z. [DOI] [PubMed] [Google Scholar]
  13. Larionov E. Nakanishi M. Katayev D. Besnard C. Kündig E. P. Scope and mechanism of asymmetric C(sp3)–H/C(Ar)–X coupling reactions: computational and experimental study. Chem. Sci. 2013;4:1995–2005. doi: 10.1039/C3SC00098B. [DOI] [Google Scholar]
  14. Katayev D. Larionov E. Nakanishi M. Besnard C. Kündig E. P. Palladium–N–Heterocyclic Carbene (NHC)–Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp3)–H Activation: Scope and DFT Study. Chem. – Eur. J. 2014;20:15021–15030. doi: 10.1002/chem.201403985. [DOI] [PubMed] [Google Scholar]
  15. Nakanishi M. Katayev D. Besnard C. Kündig E. P. Fused Indolines by Palladium–Catalyzed Asymmetric C–C Coupling Involving an Unactivated Methylene Group. Angew. Chem., Int. Ed. 2011;50:7438–7441. doi: 10.1002/anie.201102639. [DOI] [PubMed] [Google Scholar]
  16. Saget T. Lemouzy S. J. Cramer N. Chiral Monodentate Phosphines and Bulky Carboxylic Acids: Cooperative Effects in Palladium–Catalyzed Enantioselective C(sp3)–H Functionalization. Angew. Chem., Int. Ed. 2012;51:2238–2242. doi: 10.1002/anie.201108511. [DOI] [PubMed] [Google Scholar]
  17. Donets P. A. Saget T. Cramer N. Chiral monodentate trialkylphosphines based on the phospholane architecture. Organometallics. 2012;31:8040–8046. doi: 10.1021/om3008772. [DOI] [Google Scholar]
  18. Anas S. Cordi A. Kagan H. B. Enantioselective synthesis of 2-methyl indolines by palladium catalysed asymmetric C(sp3)–H activation/cyclisation. Chem. Commun. 2011;47:11483–11485. doi: 10.1039/C1CC14292E. [DOI] [PubMed] [Google Scholar]
  19. Kong W. J. Finger L. H. Oliveira J. C. A. Ackermann L. Rhodaelectrocatalysis for annulative C–H activation: polycyclic aromatic hydrocarbons through versatile double electrocatalysis. Angew. Chem., Int. Ed. 2019;58:6342–6346. doi: 10.1002/anie.201901565. [DOI] [PubMed] [Google Scholar]
  20. Fukutani T. Hirano K. Satoh T. Miura M. Synthesis of highly substituted naphthalene and anthracene derivatives by rhodium-catalyzed oxidative coupling of arylboronic acids with alkynes. Org. Lett. 2009;11:5198–5201. doi: 10.1021/ol9021172. [DOI] [PubMed] [Google Scholar]
  21. Fukutani T. Hirano K. Satoh T. Miura M. Synthesis of highly substituted acenes through rhodium-catalyzed oxidative coupling of arylboron reagents with alkynes. J. Org. Chem. 2011;76:2867–2874. doi: 10.1021/jo200339w. [DOI] [PubMed] [Google Scholar]
  22. Pedroni J. Boghi M. Saget T. Cramer N. Access to β–Lactams by Enantioselective Palladium(0)–Catalyzed C(sp3)–H Alkylation. Angew. Chem., Int. Ed. 2014;53:9064–9067. doi: 10.1002/anie.201405508. [DOI] [PubMed] [Google Scholar]
  23. Pedroni J. Cramer N. Chiral γ–Lactams by Enantioselective Palladium (0)–Catalyzed Cyclopropane Functionalizations. Angew. Chem., Int. Ed. 2015;54:11826–11829. doi: 10.1002/anie.201505916. [DOI] [PubMed] [Google Scholar]
  24. Romanov-Michailidis F. Ravetz B. D. Paley D. W. Rovis T. Ir(iii)-catalyzed carbocarbation of alkynes through undirected double C–H bond activation of anisoles. J. Am. Chem. Soc. 2018;140:5370–5374. doi: 10.1021/jacs.8b02716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Moon S. Kato M. Nishii Y. Miura M. Synthesis of Benzo[b]thiophenes through Rhodium–Catalyzed Three–Component Reaction using Elemental Sulfur. Adv. Synth. Catal. 2020;362:1669–1673. doi: 10.1002/adsc.202000112. [DOI] [Google Scholar]
  26. Liu B. Yang L. Dong Z. Chang J. Li X. Rh(iii)-Catalyzed Annulation of 2-Biphenylboronic Acid with Diverse Activated Alkenes. Org. Lett. 2021;23:7199–7204. doi: 10.1021/acs.orglett.1c02597. [DOI] [PubMed] [Google Scholar]
  27. Liu X. Zhou B. Yan K. Wen J. Li Q. Wang X. Wang X. Application of Sulfoxonium Ylides or Iodonium Ylides in Rhodium–Catalyzed Synthesis of Phenanthrenes. Adv. Synth. Catal. 2024;366:1744–1750. doi: 10.1002/adsc.202301451. [DOI] [Google Scholar]
  28. Ming J. Hayashi T. Aryloxymethyltrifluoroborates for Rhodium-Catalyzed Asymmetric Conjugate Arylation. o-Methoxyarylation through 1,4-Rhodium Shift. Org. Lett. 2016;18:6452–6455. doi: 10.1021/acs.orglett.6b03347. [DOI] [PubMed] [Google Scholar]
  29. Molander G. A. Shin I. Potassium Boc-Protected Secondary Aminomethyltrifluoroborates: Synthesis and Suzuki–Miyaura Cross-Coupling Reactions. Org. Lett. 2012;14:4458–4461. doi: 10.1021/ol301955s. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ackermann L. Carboxylate-assisted transition-metal-catalyzed C–H bond functionalizations: mechanism and scope. Chem. Rev. 2011;111:1315–1345. doi: 10.1021/cr100412j. [DOI] [PubMed] [Google Scholar]
  31. Lapointe D. Fagnou K. Overview of the mechanistic work on the concerted metallation–deprotonation pathway. Chem. Lett. 2010;39:1118–1126. doi: 10.1246/cl.2010.1118. [DOI] [Google Scholar]
  32. Walsh A. P. Jones W. D. Mechanistic Insights of a Concerted Metalation–Deprotonation Reaction with [Cp*RhCl2]2. Organometallics. 2015;34:3400–3407. doi: 10.1021/acs.organomet.5b00369. [DOI] [Google Scholar]
  33. Allinger N. L. Eliel E. L. Table of Conformational Energies. Top. Stereochem. 1967;1:199–222. [Google Scholar]
  34. Budiman Y. P. Perutz R. N. Steel P. G. Radius U. Marder T. B. Applications of Transition Metal-Catalyzed ortho-Fluorine-Directed C–H Functionalization of (Poly)fluoroarenes in Organic Synthesis. Chem. Rev. 2024;124:4822–4862. doi: 10.1021/acs.chemrev.3c00793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Clot E. Mégret C. Einstein O. Perutz R. N. Exceptional Sensitivity of Metal-Aryl Bond Energies to ortho-Fluorine Substituents: Influence of the Metal, the Coordination Sphere, and the Spectator Ligands on M–C/H–C Bond Energy Correlations. J. Am. Chem. Soc. 2009;131:7817–7827. doi: 10.1021/ja901640m. [DOI] [PubMed] [Google Scholar]
  36. MacKenzie I. A. Wang L. Onuska N. P. R. Williams O. F. Begam K. Moran A. M. Dunietz B. D. Nicewicz D. A. Discovery and Characterization of an Acridine Radical Photoreductant. Nature. 2020;580:76–80. doi: 10.1038/s41586-020-2131-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Simmons E. M. Hartwig J. F. On the Interpretation of Deuterium Kinetic Isotope Effects in C–H Bond Functionalizations by Transition-Metal Complexes. Angew. Chem., Int. Ed. 2012;51:3066–3072. doi: 10.1002/anie.201107334. [DOI] [PubMed] [Google Scholar]
  38. Pham M. V. Ye B. Cramer N. Access to Sultams by Rhodium(iii)-Catalyzed Directed C–H Activation. Angew. Chem., Int. Ed. 2012;51:10610–10614. doi: 10.1002/anie.201206191. [DOI] [PubMed] [Google Scholar]
  39. Pham M. V. Cramer N. Aromatic Homologation by Non-Chelate-Assisted RhIII-Catalyzed C–H Functionalization of Arenes with Alkynes. Angew. Chem., Int. Ed. 2014;53:3484–3487. doi: 10.1002/anie.201310723. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

QO-OLF-D6QO01119E-s001
QO-OLF-D6QO01119E-s001.pdf (13.5MB, pdf)

Data Availability Statement

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information: experimental procedures, characterization data, and figures including NMR spectra and HPLC traces. See DOI: https://doi.org/10.1039/d6qo01119e.

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