Electrooxidative Allene Annulations by Mild Cobalt-Catalyzed C–H

Subscriber access provided by UNIVERSITY OF TOLEDO LIBRARIES

Article

Electrooxidative Allene Annulations by Mild Cobalt-Catalyzed C–H Activation Tjark H. Meyer, João C. A. Oliveira, Samaresh Chandra Sau, Nate W. J. Ang, and Lutz Ackermann ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b03066 • Publication Date (Web): 15 Aug 2018 Downloaded from http://pubs.acs.org on August 15, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

Electrooxidative Allene Annulations by Mild Cobalt-Catalyzed C–H Activation Tjark H. Meyer, João C. A. Oliveira, Samaresh Chandra Sau, Nate W. J. Ang and Lutz Ackermann* Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstraße 2, 37077, Göttingen (Germany). Supporting Information Placeholder ABSTRACT: Versatile cobalt catalysis enabled the electrochemical C–H activation with allenes. Thus, allene annulations were accomplished in terms of C–H/N–H functionalizations with excellent levels of chemo-, site- and regio-selectivities under exceedingly mild conditions. Detailed mechanistic studies were conducted, including reactions with isotopicallylabeled compounds, kinetic investigations and in-operando infrared spectroscopic studies. Further, computational studies were supportive of a non-rate-determining C–H cleavage and gave key insights into the regio-selectivity of the allene annulation. The practical utility of the user-friendly approach was furthermore highlighted by gram-scale electrocatalsis.

KEYWORDS: C–H activation, allene, cobalt, cyclic voltammetry, DFT computation, electrochemistry, mechanism

INTRODUCTION Allenes have been recognized as key structural motifs in molecular syntheses,1,2 which also feature prominently in functional materials3 and bioactive4 compounds.5 In contrast to their increasing practical importance, syntheses with allenes continue to be dominated by lengthy, classical transformations relying on prefunctionalized substrates. A more operation-economical approach is represented by direct C–H activations6 with allenes, predominantly exploiting precious transition metal catalysts based on noble iridium,7 rhodium,8 palladium9 and ruthenium.10 While considerable recent progress was further realized by catalysts of earth-abundant metals11–14 all oxidative C–H activation reactions with allenes are restricted to equimolar quantities of chemical oxidants, such as toxic and/or expensive copper(II) or silver(I) salts. Thereby, stoichiometric amounts of undesired byproducts are unfortunately formed, which jeopardize the atomefficient nature of the C–H activation approach. In recent years, electrosynthesis15 has resurfaced as an increasingly potent tool in chemical16 synthesis. While electrochemical C–H activations17 were recently accomplished with alkenes18 and alkynes,19 C–H functionalizations that employ synthetically meaningful allenes20 by means of electrocatalysis have unfortunately not been accomplished thus far. Within our program towards sustainable C–H activation,21 we now unraveled the first electrocatalytic C–H activation employing allenes, which we disclose herein (Figure 1).

Figure 1. Electrochemical cobalt-catalyzed C–H/N–H annulation with allenes.

Salient features of our report comprise (a) oxidative C– H/N–H transformations for electrochemical allene annulations, (b) cost-effective, earth-abundant cobalt catalysis, (c) mild reaction conditions, (d) most user-friendly undivided cell set-up, and (e) key mechanistic insights into electrochemical allene transformations by experiment and computation. It is furthermore noteworthy that detailed computational studies rationalized the chemo- and regio-selectivity of the key elementary allene functionalization step (Scheme 1).

ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Scheme 1. Other possible C–H activations with allenes.

Page 2 of 10 Co(OAc)2∙4H2O

MeOH

0

14

–

MeOH

0

–

15

Co(OAc)2∙4H2O

MeOH

49

55

68

j

16

Co(OAc)2∙4H2O

MeOH

–

f,g,h

13

i

91

a

RESULTS AND DISCUSSION Optimization Studies. We initiated our studies by exploring different parameters for the envisioned C–H/N–H activation for the annulation of allene 2a (Table 1 and Tables S1–S4 in the Supporting Information).22 Preliminary experiments revealed that an operationally simple undivided cell set-up proved viable without major interference arising from cathodic electro-deposition, which predominantly occurred when using precious metals. A higher current led to diminished yields of the desired product 3aa. While a RVC anode was found to be beneficial, different cobalt(II) and cobalt(III) salts could be employed as the pre-catalyst. A variety of solvents was suitable for the electrochemical C–H activation, ranging from apolar CH2Cl2 and THF to polar protic alcohols. Thus, optimal reaction conditions involved MeOH as the solvent and NaOPiv23 as the additive. Thereby, the catalyst loading could be further significantly reduced. Control experiments verified the key role of the electricity and the cobalt complex.

Reaction conditions: 1 (0.3 mmol), 2 (1.2 equiv), [Co] (20 mol %), base (2.0 equiv), solvent (5.0 mL), 23°C, 9 h, constant current electrolysis (CCE) at 2 mA, undivided cell, 1 RVC anode, Pt-plate cathode. Conversion determined by HNMR analysis using 1,3,5-trimethoxybenzene as the internal b c standard; yields of isolated products in italics. 4 mA, 4.5 h. d e f Pt anode, Pt cathode. [Co] (10 mol %). 40 °C. 1 (0.5 mmol), g h i 15 h. Without current. Under nitrogen atmosphere. Dividj ed cell. Constant potential electrolysis (CPE) at 1.3 V. RVC = reticulated vitreous carbon, PyO = pyridine-1-oxide. FE = Faradaic efficiency.

With the optimal reaction conditions being identified, we probed the N-substitution pattern on benzamides 1. Thus, we confirmed the superior nature of the pyridyl-Noxide 1a, which was solely matched by benzhydrazide 1f, albeit with slightly decreased efficacy (Scheme 2). Scheme 2. N-Substitution pattern power for the C– H/N–H activation.

Table 1. Electrochemical C–H/N–H activation with allenes: Optimization.a

entry

[Co]

solvent

FE [%]

yield [%]

1

Co(OAc)2∙4H2O

TFE

64

82, 72

2

Co(OAc)2∙4H2O

TFE

44

49

3

Co(OAc)2∙4H2O

TFE

2

3

4

Co(acac)2

TFE

45

50

5

Co(acac)3

TFE

36

40

6

CoBr2

TFE

63

70

7

[Cp*Co(CO)I2]

TFE

55

62

8

Co(OAc)2∙4H2O

CH2Cl2

65

73

9

Co(OAc)2∙4H2O

THF

62

69

10

Co(OAc)2∙4H2O

MeOH

71

78

11

Co(OAc)2∙4H2O

MeOH

71

12

Co(OAc)2∙4H2O

MeOH

81

b

c

85, 79

Versatility. Thereafter, we studied the robustness of the C–H activation approach (Scheme 3). Hence, we were delighted to observe efficient annulations of allene 2a by differently decorated benzamides 1, being fully tolerant of functional groups, including iodo, thioether, ester and enolazible ketone substituents. The versatile cobalt catalyst performed with excellent levels of position control. The electrochemical C–H/N–H activation was not limited to arenes. Indeed, heterocycles and alkenes were likewise identified as amenable substrates to furnish the desired products 3va and 3wa, respectively. Intramolecular competition experiments with meta-substituted arenes 1p-1r occurred with unique site-selectivity through steric interactions (3pa), unless a secondary directing group effect was operative (3qa, 3ra).

d,e

d,e,f

92, 91

ACS Paragon Plus Environment

Page 3 of 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

Scheme 3. Electrochemical C–H/N–H activation with benz- and acrylamides 1.

Scheme 4. Electrochemical allene annulation.

a

Co(OAc)2∙4H2O (20 mol %).

Moreover, the cobalt-catalyzed electrochemical C–H activation was also accomplished with more challenging internal allenes 2 (Scheme 5). Interestingly, here the cobalt catalysts delivered the corresponding exo-methylene isoquinolones 4, providing instrumental mechanistic information on the migratory allene insertion/isomerization manifold. Scheme 5. Electrochemical C–H/N–H activation with internal allenes 2. The robustness and versatility of the electrochemical C– H activation were reflected by enabling the smooth annulation of diversely substituted allenes 2 (Scheme 4). Thus, decorated allenes 2 delivered the desired products 3 with complete control of the chemo- and regio-selectivity, thus solely occurring at the allene’s terminal position. The connectivity of the isoquinolones 3 was unambiguously established using inter alia detailed 2D-NMR spectroscopic and X-ray diffraction analysis.

ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 10

Mechanistic Studies by Experiment. Given the versatility of the first electrochemical C–H activation with allenes 2, we became attracted to rationalizing its mode of action. Hence, electrochemical C–H/N–H activation in the presence of isotopically labeled cosolvent led to deuterium incorporation solely in the benzylic position by facile post-catalysis H/D exchange (Scheme 6a). Intermolecular competition studies revealed the inherently increased reactivity of electron-rich arenes 1h and 1g (Scheme 6b), which can be rationalized in terms of a base-assisted internal electrophilic-type substitution (BIES) C–H metalation.24 In-operando infrared spectroscopic studies showed that a significant induction period was not of relevance, highlighting an initial rate of 1.53⋅⋅10-2 mol⋅⋅sec-1 (Scheme 6c). Furthermore, studies directed towards elucidating a kinetic isotope effect (KIE) were indicative of a non-rate-determining C–H cleavage (Scheme 6d). Scheme 6. Summary of key mechanistic findings.

Moreover, we tested the oxidative electrochemical cobalt-catalyzed C–H transformation by means of cyclic voltammetry (Figure 2). Substrate 1a gave rise to an irreversible oxidation at 1.51 VSCE, whereas allene 2a did not show any relevant oxidation in MeOH. The cobalt precatalyst, however, revealed an irreversible oxidation peak at 1.19 VSCE, which is in good agreement with previous reports,25 and is likely due to carboxylate adsorption on the electrode. A mixture of the cobalt complex and substrate 1a did not affect the oxidation potential of the cobalt complex, being indicative of a key anodic oxidation towards cobalt(III) carboxylate species. Moreover, irreversible oxidation of product 3aa was observed at potentials beyond 1.44 VSCE, and of allene 2e at potential of 1.60 VSCE (Table S4), rendering mild constant-potential electrocatalysis an alternative.

ACS Paragon Plus Environment

Page 5 of 10

ACS Catalysis –1

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 2. Cyclic voltammetry at 100 mV s in MeOH. (a) Impact of reaction components. (b) Different allenes 2.

The migratory insertion of allene 2c was shown to occur with excellent regio-selectivity. The insertion distal to the allene’s substituent (Figure 3a) is favored by 2.2 kcal mol-1 compared to the one proximal to the allene’s substituent (Figure 3b). Notably, our findings were indicative of a plausible spin cross-over scenario (Figure 3a). This allows the allene insertion transition-state to proceed through a singlet spin-state pathway, which is favored by 3.3 kcal mol-1 with regard to the overall most stable triplet spinstate, leading to a more facile allene insertion.

Computational Mechanistic Studies. In addition, we probed the catalyst’s working mode by means of computational studies on the PW6B95-D3BJ/def2-TZVPSMD(MeOH)//PBE0-D3BJ/def2-SVP level of theory.26 A close assessment of the reaction path between the allene insertion and the reductive elimination elementary steps (Figure 3a) reveals that the allene insertion is the rate-determining step, featuring an activation barrier of 16 kcal mol-1 versus 7.7 kcal mol-1 for a reductive elimination. a)

b)

O

N N O CoIII OPiv CO2Et

O

O

N N CoIII O

N N CoIII O

OPiv

OPiv

EtO2C O

EtO2C

N N O CoIII OPiv

O

N

N O CoI EtO2C OPiv

EtO2C

insertion

N N O CoIII OPiv

O

CO2Et

insertion

reductive elimination –1

Figure 3. Computed Gibbs free energies (ΔG313.15) in kcal mol for the regio-selective allene annulation. All values include dispersion corrections. In the computed transition-state structures non-relevant hydrogens were omitted for clarity.

Proposed Catalytic Cycle for Electrooxidative Allene Annulation. Based on our experimental and computational mechanistic studies, we propose the electrochemical C–H/N–H activation to commence by anodic cobalt oxidation, which sets the stage for an efficient BIES-C–H scission by carboxylate24 assistance (Scheme 7). Then, migratory insertion of allene 2 and reductive elimination deliver the exo-methylene isoquinolone 4 (vide supra), which upon isomerization provides the desired product 3. The active cobalt catalyst is thereafter regenerated by the key anodic oxidation, producing H2 as the only byproduct. Our approach thus prevents metal-based terminal oxidants towards atom- and step-efficient C–H activation.

Scheme 7. Proposed catalytic cycle. CoII(OPiv)2

cathodic reduction

OPiv

1a

anodic oxidation O

2H

H2

N H

CoIII(OPiv)3 5

anodic oxidation

H

N O

2 HOPiv

C H cleavage

2 HOPiv O CoI(OPiv) 8 O N

4

N O

6

reductive elimination

R

OPiv isomerization HOPiv

insertion • O

N N O CoIII OPiv

3aa R 7

ACS Paragon Plus Environment

N N CoIII O OPiv

R 2

BIES

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Gram-Scale Reaction. Finally, the user-friendly nature of our electrochemical C–H/N–H activation was illustrated by the gram-scale electrocatalytic preparation of product 3la with similar levels of efficiency (Scheme 8). Scheme 8. Gram-scale electrochemical allene annulation.

CONCLUSIONS In conclusion, we have devised the first electrocatalytic C–H activation with allenes. Thus, a robust cobalt catalyst allowed for C–H/N–H functionalizations on arenes, heteroarenes and alkenes with broad substrate scope. The allene annulation was characterized by excellent levels of chemo-, position-, and regio-selectivity. Detailed mechanistic studies by experiment and computation were supportive of a fast C–H cleavage by carboxylate assistance and rationalized the regio-selectivity of the allene annulation.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Detailed experimental procedures, compound characterization data, and computational analysis (PDF) Data for C30H27N2O4P

AUTHOR INFORMATION Corresponding Author * E-mail: [email protected]

Notes The authors declare no competing financial interests.

ACKNOWLEDGMENT Generous support by the DFG (Gottfried-Wilhelm-Leibniz prize), and the Science and Engineering Research Board (fellowship to S.C.S.) is gratefully acknowledged. We thank Dr. Christopher Golz (University Göttingen) for assistance with the X-ray diffraction analysis.

REFERENCES (1) (a) Yang, B.; Qiu, Y.; Bäckvall, J.-E. Control of Selectivity in Palladium(II)-Catalyzed Oxidative Transformations of Allenes. Acc. Chem. Res. 2018, 51, 1520-1531; (b) Ye, J.; Ma, S. Palladium-Catalyzed Cyclization Reactions of Allenes in the Presence of Unsaturated Carbon−Carbon Bonds. Acc. Chem. Res.

Page 6 of 10

2014, 47, 989-1000; (c) Yu, S.; Ma, S. Allenes in Catalytic Asymmetric Synthesis and Natural Product Syntheses. Angew. Chem. Int. Ed. 2012, 51, 3074-3112; (d) Aubert, C.; Fensterbank, L.; Garcia, P.; Malacria, M.; Simonneau, A. Transition Metal Catalyzed Cycloisomerizations of 1,n-Allenynes and -Allenenes. Chem. Rev. 2011, 111, 1954-1993; (e) Ma, S. Some Typical Advances in the Synthetic Applications of Allenes. Chem. Rev. 2005, 105, 28292872. (2) (a) Hoffmann-Röder, A.; Krause, N. Synthesis and Properties of Allenic Natural Products and Pharmaceuticals. Angew. Chem. Int. Ed. 2004, 43, 1196-1216; (b) Hashmi, A. S. K. New and Selective Transition Metal Catalyzed Reactions of Allenes. Angew. Chem. Int. Ed. 2000, 39, 3590-3593. (3) Rivera-Fuentes, P.; Diederich, F. Allenes in Molecular Materials. Angew. Chem. Int. Ed. 2012, 51, 2818-2828. (4) For examples of allenes in natural product synthesis, see: (a) Li, Y.; Dai, M. Total Syntheses of the Reported Structures of Curcusones I and J through Tandem Gold Catalysis. Angew. Chem. Int. Ed. 2017, 56, 11624-11627; (b) Suto, T.; Yanagita, Y.; Nagashima, Y.; Takikawa, S.; Kurosu, Y.; Matsuo, N.; Sato, T.; Chida, N. Unified Total Synthesis of Madangamines A, C, and E. J. Am. Chem. Soc. 2017, 139, 2952-2955; (c) Cai, L.; Zhang, K.; Kwon, O. Catalytic Asymmetric Total Synthesis of (−)Actinophyllic Acid. J. Am. Chem. Soc. 2016, 138, 3298-3301; (d) Ahlers, A.; Haro, T.; Gabor, B.; Fürstner, A. Concise Total Synthesis of Enigmazole A. Angew. Chem. Int. Ed. 2016, 55, 14061411; (e) Haydl, A. M.; Breit, B. Atom-Economical Dimerization Strategy by the Rhodium-Catalyzed Addition of Carboxylic Acids to Allenes: Protecting-Group-Free Synthesis of Clavosolide A and Late-Stage Modification. Angew. Chem. Int. Ed. 2015, 54, 1553015534. (5) Krause, N.; Hashmi, A. S. K. Modern Allene Chemistry. Wiley-VCH: Weinheim, 2004. (6) (a) Gandeepan, P.; Ackermann, L. Transient Directing Groups for Transformative C–H Activation by Synergistic Metal Catalysis. Chem 2018, 4, 199-222; (b) Chu, J. C. K.; Rovis, T. Complementary Strategies for Directed C(sp3)−H Functionalization: A Comparison of Transition-Metal-Catalyzed Activation, Hydrogen Atom Transfer, and Carbene/Nitrene Transfer. Angew. Chem. Int. Ed. 2018, 57, 62-101; (c) Wei, Y.; Hu, P.; Zhang, M.; Su, W. Metal-Catalyzed Decarboxylative C–H Functionalization. Chem. Rev. 2017, 117, 8864-8907; (d) Ma, W.; Gandeepan, P.; Li, J.; Ackermann, L. Recent Advances in Positional-Selective Alkenylations: Removable Guidance for Twofold C–H Activation. Org. Chem. Front. 2017, 4, 1435-1467; (e) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu, J.-Q. PalladiumCatalyzed Transformations of Alkyl C–H Bonds. Chem. Rev. 2017, 117, 8754-8786; (f) Park, Y.; Kim, Y.; Chang, S. Transition MetalCatalyzed C–H Amination: Scope, Mechanism, and Applications. Chem. Rev. 2017, 117, 9247-9301; (g) Zheng, Q.-Z.; Jiao, N. AgCatalyzed C–H/C–C Bond Functionalization. Chem. Soc. Rev. 2016, 45, 4590-4627; (h) Ye, B.; Cramer, N. Chiral Cyclopentadienyls: Enabling Ligands for Asymmetric Rh(III)Catalyzed C–H Functionalizations. Acc. Chem. Res. 2015, 48, 1308-1318; (i) Rouquet, G.; Chatani, N. Catalytic Functionalization of C(sp2)–H and C(sp3)–H Bonds by Using Bidentate Directing Groups. Angew. Chem. Int. Ed. 2013, 52, 11726-11743; (j) Hickman, A. J.; Sanford, M. S. High-valent Organometallic Copper and Palladium in Catalysis. Nature 2012, 484, 177; (k) Morton, D.; Davies, H. M. L. Guiding Principles for Site Selective and Stereoselective Intermolecular C–H Functionalization by Donor/Acceptor Rhodium Carbenes. Chem. Soc. Rev. 2011, 40, 1857-1869; (l) Lyons, T. W.; Sanford, M. S. Palladium-Catalyzed Ligand-Directed C−H Functionalization Reactions. Chem. Rev. 2010, 110, 1147-1169; (m) Daugulis, O.; Do, H. Q.; Shabashov, D. Palladiumand Copper-Catalyzed Arylation of Carbon−Hydrogen Bonds. Acc. Chem. Res. 2009, 42, 1074–1086;

ACS Paragon Plus Environment

Page 7 of 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

(n) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Palladium(II)Catalyzed C–H Activation/C–C Cross-Coupling Reactions: Versatility and Practicality. Angew. Chem. Int. Ed. 2009, 48, 5094-5115; (o) Ackermann, L.; Vicente, R.; Kapdi, A. R. Transition-Metal-Catalyzed Direct Arylation of (Hetero)Arenes by C–H Bond Cleavage. Angew. Chem. Int. Ed. 2009, 48, 97929826; (p) Bergman, R. G. Organometallic Chemistry: C–H Activation. Nature 2007, 446, 391; and cited references. (7) Zhang, Y. J.; Skucas, E.; Krische, M. J. Direct Prenylation of Aromatic and α,β-Unsaturated Carboxamides via Iridium-Catalyzed C−H Oxidative Addition−Allene Insertion. Org. Lett. 2009, 11, 4248-4250. (8) (a) Kong, D. S.; Wang, Y. F.; Zhao, Y. S.; Li, Q. H.; Chen, Y. X.; Tian, P.; Lin, G. Q. Bisannulation of Benzamides and Cyclohexadienone-Tethered Allenes Triggered by Cp*Rh(III)Catalyzed C–H Activation and Relay Ene Reaction. Org. Lett. 2018, 20, 1154-1157; (b) Jai, Z.-J.; Merten, C.; Gontla, R.; Danilicu, C. G.; Antonchick, A. P.; Waldmann, H. General Enantioselective C−H Activation with Efficiently Tunable Cyclopentadienyl Ligands. Angew. Chem. Int. Ed. 2017, 56, 2429-2434; (c) Zhou, Z.; Liu, G.; Lu, X. Regiocontrolled Coupling of Aromatic and Vinylic Amides with α-Allenols To Form γ-Lactams via Rhodium(III)Catalyzed C–H Activation. Org. Lett. 2016, 18, 5668-5671; (d) Ye, B.; Cramer, N. A Tunable Class of Chiral Cp Ligands for Enantioselective Rhodium(III)-Catalyzed C–H Allylations of Benzamides. J. Am. Chem. Soc. 2013, 135, 636-639; (e) Wang, H.; Beiring, B.; Yu, D. G.; Collins, K. D.; Glorius, F. [3]Dendralene Synthesis: Rhodium(III)-Catalyzed Alkenyl C–H Activation and Coupling Reaction with Allenyl Carbinol Carbonate. Angew. Chem. Int. Ed. 2013, 52, 12430-12434; (f) Zeng, R.; Ye, J.; Fu, C.; Ma, S. Arene C–H Bond Functionalization Coupling with Cyclization of Allenes. Adv. Synth. Catal. 2013, 355, 1963-1970; (g) Zeng, R.; Fu, C.; Ma, S. Highly Selective Mild Stepwise Allylation of N-Methoxybenzamides with Allenes. J. Am. Chem. Soc. 2012, 134, 9597-600; (h) Wang, H.; Glorius, F. Mild Rhodium(III)Catalyzed C–H Activation and Intermolecular Annulation with Allenes. Angew. Chem. Int. Ed. 2012, 51, 7318-7322; (i) Tran, D. N.; Cramer, N. syn-Selective Rhodium(I)-Catalyzed Allylations of Ketimines Proceeding through a Directed C–H Activation/Allene Addition Sequence. Angew. Chem. Int. Ed. 2010, 49, 8181-8184. (9) (a) Qiu, Y.; Mendoza, A.; Posevins, D.; Himo, F.; Kalek, M.; Bäckvall, J. E. Mechanistic Insight into Enantioselective Palladium-Catalyzed Oxidative Carbocyclization–Borylation of Enallenes. Chem. Eur. J. 2018, 24, 2433-2439; (b) Xia, X. F.; Wang, Y. Q.; Zhang, L. L.; Song, X. R.; Liu, X. Y.; Liang, Y. M. PalladiumCatalyzed C–H Activation and Intermolecular Annulation with Allenes. Chem. Eur. J. 2014, 20, 5087-5091; (c) Rodriguez, A.; Albert, J.; Ariza, X.; Garcia, J.; Granell, J.; Farras, J.; La Mela, A.; Nicolas, E. Catalytic C–H Activation of Phenylethylamines or Benzylamines and Their Annulation with Allenes. J. Org. Chem. 2014, 79, 9578-9585; (d) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Palladium-Catalyzed Reactions of Allenes. Chem. Rev. 2000, 100, 3067-3126. (10) Nakanowatari, S.; Ackermann, L. Ruthenium(II)Catalyzed C–H Functionalizations with Allenes: Versatile Allenylations and Allylations. Chem. Eur. J. 2015, 21, 16246-16251. (11) (a) Kuppusamy, R.; Santhoshkumar, R.; Boobalan, R.; Wu, H.-R.; Cheng, C.-H. Synthesis of 1,2-Dihydroquinolines by Co(III)-Catalyzed [3 + 3] Annulation of Anilides with Benzylallenes. ACS Catal. 2018, 8, 1880-1883; (b) Zhai, S.; Qiu, S.; Chen, X.; Tao, C.; Li, Y.; Cheng, B.; Wang, H.; Zhai, H. Trifunctionalization of Allenes via Cobalt-Catalyzed MHPAssisted C–H Bond Functionalization and Molecular Oxygen Activation. ACS Catal. 2018, 8, 6645–6649; (c) Yao, X.; Jin, L.; Rao, Y. Synthesis of Phosphaisoquinolin-1-one by Annulation of Aryl Phosphinamides with Allenes through a Cobalt-Promoted C−H Functionalization. Asian J. Org. Chem. 2017, 6, 825-830; (d)

Thrimurtulu, N.; Nallagonda, R.; Volla, C. M. Cobalt-Catalyzed Aryl C–H Activation and Highly Regioselective Intermolecular Annulation of Sulfonamides with Allenes. Chem. Commun. 2017, 53, 1872-1875; (e) Boobalan, R.; Ramajayam, K.; Santhoshkumar, R.; Gandeepan, P.; Cheng, C.-H. Access to Isoquinolin-1(2 H)ones and Pyridones by Cobalt-Catalyzed Oxidative Annulation of Amides with Allenes. ChemCatChem 2017, 9, 273-277; (f) Nakanowatari, S.; Mei, R.; Feldt, M.; Ackermann, L. Cobalt(III)Catalyzed Hydroarylation of Allenes via C–H Activation. ACS Catal. 2017, 7, 2511-2515; (g) Li, T.; Zhang, C.; Tan, Y.; Pan, W.; Rao, Y. Cobalt-Catalyzed C–H Activation and Regioselective Intermolecular Annulation with Allenes. Org. Chem. Front. 2017, 4, 204-209; (h) Lan, T.; Wang, L.; Rao, Y. Regioselective Annulation of Aryl Sulfonamides with Allenes through CobaltPromoted C–H Functionalization. Org. Lett. 2017, 19, 972-975; (i) Thrimurtulu, N.; Dey, A.; Maiti, D.; Volla, C. M. CobaltCatalyzed sp2-C−H Activation: Intermolecular Heterocyclization with Allenes at Room Temperature. Angew. Chem. Int. Ed. 2016, 55, 12361-12365. (12) Nakanowatari, S.; Müller, T.; Oliveira, J. C. A.; Ackermann, L. Bifurcated Nickel-Catalyzed Functionalizations: Heteroarene C−H Activation with Allenes. Angew. Chem. Int. Ed. 2017, 56, 15891-15895. (13) (a) Shi‐Yong, C.; Xiang‐Lei, H.; Jia‐Qiang, W.; Qingjiang, L.; Yunyun, C.; Honggen, W. Manganese(I)-Catalyzed Regio- and Stereoselective 1,2-Diheteroarylation of Allenes: Combination of C−H Activation and Smiles Rearrangement. Angew. Chem. Int. Ed. 2017, 56, 9939-9943; (b) Chen, S.‐Y.; Li, Q..; Liu, X.‐G.; Wu, J.‐Q.; Zhang, S.‐S.; Wang, H. Polycyclization Enabled by Relay Catalysis: One-Pot Manganese-Catalyzed C−H Allylation and Silver-Catalyzed Povarov Reaction. ChemSusChem 2017, 10, 2360-2364; (c) Chen, S. Y.; Li, Q.; Wang, H. Manganese(I)-Catalyzed Direct C–H Allylation of Arenes with Allenes. J. Org. Chem. 2017, 82, 11173-11181. (14) Mo, J.; Müller, T.; Oliveira, J. C. A.; Ackermann, L. 1,4Iron Migration for Expedient Allene Annulations through IronCatalyzed C−H/N−H/C−O/C−H Functionalizations. Angew. Chem. Int. Ed. 2018, 57, 7719-7723. (15) For representative reviews, see: (a) Ma, C.; Fang, P.; Mei, T.-S. Recent Advances in C–H Functionalization Using Electrochemical Transition Metal Catalysis. ACS Catal. 2018, 8, 7179-7189; (b) Sauermann, N.; Meyer, T. H.; Qiu, Y.; Ackermann, L. Electrocatalytic C–H Activation. ACS Catal. 2018, 8, 7086-7103; (c) Waldvogel, S. R.; Möhle, S.; Zirbes, M.; Rodrigo, E.; Gieshoff, T.; Wiebe, A. Modern Electrochemical Aspects for the Synthesis of Value-Added Organic Products. Angew. Chem. Int. Ed. 2018, 57, 6018-6041; (d) Kärkäs, M. D. Electrochemical Strategies for C– H Functionalization and C–N Bond Formation. Chem. Soc. Rev. 2018, 47, 5786-5865; (e) Jiang, Y.; Xu, K.; Zeng, C. Use of Electrochemistry in the Synthesis of Heterocyclic Structures. Chem. Rev. 2018, 118, 4485-4540; (f) Yang, Q.-L.; Fang, P.; Mei, T.S. Recent Advances in Organic Electrochemical C–H Functionalization. Chin. J. Chem. 2018, 36, 338-352; (g) Yan, M.; Kawamata, Y.; Baran, P. S. Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance. Chem. Rev. 2017, 117, 13230-13319; (h) Jiao, K.-J.; Zhao, C.-Q.; Fang, P.; Mei, T.S. Palladium catalyzed C–H Functionalization with Electrochemical Oxidation. Tetrahedron Lett. 2017, 58, 797-802; (i) Hou, Z.-W.; Mao, Z.-Y.; Xu, H.-C. Recent Progress on the Synthesis of (Aza)indoles through Oxidative Alkyne Annulation Reactions. Synlett 2017, 28, 1867-1872; (j) Waldvogel, S. R.; Janza, B. Renaissance of Electrosynthetic Methods for the Construction of Complex Molecules. Angew. Chem. Int. Ed. 2014, 53, 7122-7123; (k) Nguyen, B. H.; Redden, A.; Moeller, K. D. Sunlight, Electrochemistry, and Sustainable Oxidation Reactions. Green Chem. 2014, 16, 69-72; (l) Francke, R.; Little, R. D. Redox Catalysis in Organic Electrosynthesis: Basic Principles and

ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Recent Developments. Chem. Soc. Rev. 2014, 43, 2492-2521; For Examples of Catalyzed Cross-coupling Reaction, see: (m) Gomes, P.; Gosmini, C.; Périchon, J. Cobalt-Catalyzed Electrochemical Vinylation of Aryl Halides using Vinylic Acetates. Tetrahedron 2003, 59, 2999-3002; (n) Gomes, P.; Fillon, H.; Gosmini, C.; Labbé, E.; Périchon, J. Synthesis of Unsymmetrical Biaryls by Electroreductive Cobalt-Catalyzed Cross-Coupling of Aryl Halides. Tetrahedron 2002, 58, 8417-8424, and references cited therehin. (16) Waldvogel, S. R.; Wiebe, A.; Gieshoff, T.; Möhle, S.; Rodrigo, E.; Zirbes, M. Electrifying Organic Synthesis. Angew. Chem. Int. Ed. 2018, 57, 5594-5619. (17) (a) Shrestha, A.; Lee, M.; Dunn, A. L.; Sanford, M. S. Palladium-Catalyzed C–H Bond Acetoxylation via Electrochemical Oxidation. Org. Lett. 2018, 20, 204-207; (b) Sauermann, N.; Mei, R.; Ackermann, L. Electrochemical C−H Amination by Cobalt Catalysis in a Renewable Solvent. Angew. Chem. Int. Ed. 2018, 57, 5090-5094; (c) Gao, X.; Wang, P.; Zeng, L.; Tang, S.; Lei, A. Cobalt(II)-Catalyzed Electrooxidative C–H Amination of Arenes with Alkylamines. J. Am. Chem. Soc. 2018, 140, 4195-4199; (d) Yang, Q.-L.; Li, Y.-Q.; Ma, C.; Fang, P.; Zhang, X.-J.; Mei, T.-S. Palladium-Catalyzed C(sp3)–H Oxygenation via Electrochemical Oxidation. J. Am. Chem. Soc. 2017, 139, 32933298; (e) Sauermann, N.; Meyer, T. H.; Tian, C.; Ackermann, L. Electrochemical Cobalt-Catalyzed C–H Oxygenation at Room Temperature. J. Am. Chem. Soc. 2017, 139, 18452-18455; (f) Li, Y.Q.; Yang, Q.-L.; Fang, P.; Mei, T.-S.; Zhang, D. PalladiumCatalyzed C(sp2)–H Acetoxylation via Electrochemical Oxidation. Org. Lett. 2017, 19 , 2905–2908; (g) Ma, C.; Zhao, C.Q.; Li, Y.-Q.; Zhang, L.-P.; Xu, X.-T.; Zhang, K.; Mei, T.-S. Palladium-Catalyzed C–H Activation/C–C Cross-Coupling Reactions via Electrochemistry. Chem. Commun. 2017, 53, 1218912192; (h) Khrizanforov, M. N.; Strekalova, S. O.; Grinenko, V. V.; Khrizanforova, V. V.; Gryaznova, T. V.; Budnikova, Y. H. Fe and Ni-Catalyzed Electrochemical Perfluoroalkylation of C–H Bonds of Coumarins. Russ. Chem. Bull. 2017, 66, 1446-1449; (i) Saito, F.; Aiso, H.; Kochi, T.; Kakiuchi, F. Palladium-Catalyzed Regioselective Homocoupling of Arenes Using Anodic Oxidation: Formal Electrolysis of Aromatic Carbon–Hydrogen Bonds. Organometallics 2014, 33, 6704-6707; (j) Aiso, H.; Kochi, T.; Mutsutani, H.; Tanabe, T.; Nishiyama, S.; Kakiuchi, F. Catalytic Electrochemical C–H Iodination and One-Pot Arylation by ON/OFF Switching of Electric Current. J. Org. Chem. 2012, 77, 7718-7724; (k) Kakiuchi, F.; Kochi, T.; Mutsutani, H.; Kobayashi, N.; Urano, S.; Sato, M.; Nishiyama, S.; Tanabe, T. PalladiumCatalyzed Aromatic C−H Halogenation with Hydrogen Halides by Means of Electrochemical Oxidation. J. Am. Chem. Soc. 2009, 131, 11310-11311. (18) (a) Qiu, Y.; Kong, W. J.; Struwe, J.; Sauermann, N.; Rogge, T.; Scheremetjew, A.; Ackermann, L. Electrooxidative Rhodium-Catalyzed C−H/C−H Activation: Electricity as Oxidant for Cross-Dehydrogenative Alkenylation. Angew. Chem. Int. Ed. 2018, 57, 5828-5832; (b) Amatore, C.; Cammoun, C.; Jutand, A. Electrochemical Recycling of Benzoquinone in the Pd/Benzoquinone-Catalyzed Heck-Type Reactions from Arenes. Adv. Synth. Catal. 2007, 349, 292-296. (19) (a) Xu, F.; Li, Y.-J.; Huang, C.; Xu, H.-C. RutheniumCatalyzed Electrochemical Dehydrogenative Alkyne Annulation. ACS Catal. 2018, 3820-3824; (b) Tian, C.; Massignan, L.; Meyer, T. H.; Ackermann, L. Electrochemical C−H/N−H Activation by Water-Tolerant Cobalt Catalysis at Room Temperature. Angew. Chem. Int. Ed. 2018, 57, 2383-2387; (c) Zhang, G.; Lin, Y.; Luo, X.; Hu, X.; Chen, C.; Lei, A. Oxidative [4+2] Annulation of Styrenes with Alkynes Under External-Oxidant-Free Conditions. Nat. Commun. 2018, 9, 1225. (d) Qiu, Y.; Tian, C.; Massignan, L.; Rogge, T.; Ackermann, L. Electrooxidative Ruthenium-Catalyzed C−H/O−H Annulation by Weak O-Coordination. Angew. Chem.

Page 8 of 10

Int. Ed. 2018, 57, 5818-5822; (e) Mei, R.; Sauermann, N.; Oliveira, J. C. A.; Ackermann, L. Electroremovable Traceless Hydrazides for Cobalt-Catalyzed Electro-Oxidative C–H/N–H Activation with Internal Alkynes. J. Am. Chem. Soc. 2018, 140, 7913-7921. (20) (a) Pattenden, G.; Robertson, G. M. Synthesis of Functionalised Cyclopentanes by Intramolecular RadicalMediated Cyclisations of Terminal Allenic Ketones. Tetrahedron 1985, 41, 4001-4011; (b) Schlegel, G.; Schäfer, H. Elektrochemische Reduktion und Oxidation von Allenen. J. Chem. Ber. 1983, 116, 960-969. (21) (a) Ackermann, L. Carboxylate-Assisted RutheniumCatalyzed Alkyne Annulations by C–H/Het–H Bond Functionalizations. Acc. Chem. Res. 2014, 47, 281-295; (b) Ackermann, L. Catalytic Arylations with Challenging Substrates: From Air-Stable HASPO Preligands to Indole Syntheses and C–H Bond Functionalizations. Synlett 2007, 4, 507-526. (22) For detailed information, see the Supporting Information. (23) (a) Ackermann, L. Carboxylate-Assisted TransitionMetal-Catalyzed C−H Bond Functionalizations: Mechanism and Scope. Chem. Rev. 2011, 111, 1315-1345; (b) Davies, D. L.; Macgregor, S. A., McMullin, C. L. Computational Studies of CarboxylateAssisted C–H Activation and Functionalization at Group 8–10 Transition Metal Centers. Chem. Rev. 2017, 117, 8649-8709. (24) (a) Tan, E.; Quinonero, O.; Elena de Orbe, M.; Echavarren, A. M. Broad-Scope Rh-Catalyzed InverseSonogashira Reaction Directed by Weakly Coordinating Groups. ACS Catal. 2018, 8, 2166-2172; (b) Zell, D.; Bursch, M.; Müller, V.; Grimme, S.; Ackermann, L. Full Selectivity Control in Cobalt(III)-Catalyzed C−H Alkylations by Switching of the C−H Activation Mechanism. Angew. Chem. Int. Ed. 2017, 56, 1037810382; (c) Ma, W.; Mei, R.; Tenti, G.; Ackermann, L. Ruthenium(II)-Catalyzed Oxidative C−H Alkenylations of Sulfonic Acids, Sulfonyl Chlorides and Sulfonamides. Chem. Eur. J. 2014, 20, 15248-15251. (25) (a) Beattie, J. K.; Beck, C. U.; Lay, P. A.; MastersA. F. Chemistry of Cobalt Acetate. 7. Electrochemical Oxidation of μ3Oxo-Centered Cobalt(III) Acetate Trimers. Inorg. Chem. 2003, 42, 8366–8370; (b) Malyszko, J. ;Michalkiewicz, S.; Goral, D.; Scendo,M. Electrochemical Characteristics of the Mn(III)/Mn(II) and Co(II)/Co(II) Systems at Platinum in Anhydrous Acetic Acid Solutions. J. Appl. Electrochem. 1998, 28, 107-113. (26) (a) Grimme, S.; Ehrlich, S.; Goerigk, L. Effect of the Damping Function in Dispersion Corrected Density Functional Theory. J. Comput. Chem. 2011, 32, 1456-1465; (b) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. A Consistent and Accurate ab initio Parametrization of Density Functional Dispersion Correction (DFT-D) for the 94 Elements H-Pu. J. Chem. Phys. 2010, 132, 154104; (c) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions. J. Phys. Chem. B 2009, 113, 6378-6396; (d) Zhao, Y.; Truhlar, D. G. Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions. J. Phys. Chem. A 2005, 109, 5656-5667; (e) Ernzerhof, M.; Scuseria, G. E. Assessment of the Perdew–Burke–Ernzerhof Exchange-Correlation Functional. J. Chem. Phys. 1999, 110, 5029-5036; (f) Adamo, C.; Barone, V. Toward Reliable Density Functional Methods without Adjustable Parameters: The PBE0 model. J. Chem. Phys. 1999, 110, 6158-6170; (g) Weigend, F. Accurate Coulomb-fitting Basis Sets for H to Rn. Phys. Chem. Chem. Phys. 2006, 8, 1057-1065; (h) Weigend, F.; Ahlrichs, R. Balanced Basis Sets of Split Valence, Triple Zeta Valence and Quadruple Zeta Valence Quality for H to Rn: Design and Assessment of Accuracy. Phys. Chem. Chem. Phys. 2005, 7, 3297-3305; (i) Schäfer, A.; Huber, C.; Ahlrichs, R. Fully

ACS Paragon Plus Environment

Page 9 of 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

Optimized Contracted Gaussian Basis Sets of Triple Zeta Valence Quality for Atoms Li to Kr. J. Chem. Phys. 1994, 100, 5829-5835; (j) Schäfer, A.; Horn, H.; Ahlrichs, R. Fully Optimized Contracted Gaussian Basis Sets for Atoms Li to Kr. J. Chem. Phys. 1992, 97, 2571-2577.

ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Paragon Plus Environment

Page 10 of 10