Palladium-Catalyzed Highly Regioselective Aromatic Substitution of

Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

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Palladium-Catalyzed Highly Regioselective Aromatic Substitution of Benzylic Ammonium Salts with Amines Ya-Nan Xu,† Meng-Zeng Zhu,† Yu-Kun Lin,† and Shi-Kai Tian*,†,‡ †

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Hefei National Laboratory for Physical Sciences at the Microscale, Center for Excellence in Molecular Synthesis, and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China ‡ Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China S Supporting Information *

ABSTRACT: An unprecedented aromatic substitution reaction of benzylic ammonium salts has been developed through palladiumcatalyzed C−N bond cleavage. A range of primary and secondary amines participated in a palladium-catalyzed aromatic substitution reaction of benzylic ammonium salts, delivering sterically hindered aromatic amines in moderate to excellent yields with extremely high regioselectivity. Preliminary mechanistic studies permitted successful identification of π-benzylpalladium complexes and γ-vinyl allylic amines as key intermediates. This study paves the way for the use of benzylic ammonium salts in the aromatic substitution reactions.

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benzylic ammonium salts serve as effective benzylating agents to couple with alkenes,6a aromatics,6b,k,m aldehydes,6p CO2,6f,p,r CO,6l organoborons,4h,k,6b−e,g−j,q and sulfur nucleophiles,6n,o offering a functional group handle orthogonal to benzylic halides and alcohol derivatives. Herein, we report for the first time an aromatic substitution reaction of benzylic ammonium salts through palladium-catalyzed C−N bond cleavage (Scheme 1b). In the course of exploring new C−N bond cleavage reactions of quaternary ammonium salts,5l,m,9 we unexpectedly found that the PdCl2/PPh3-catalyzed reaction of benzylic ammonium salt 1a with dialkylamine 2a afforded tertiary aromatic amine 3a, instead of the corresponding tertiary benzylic amine, in 70% yield (Table 1, entry 1). This reaction represents the first example of an aromatic substitution reaction of benzylic ammonium salts via C−N bond cleavage, offers a functional group handle orthogonal to the corresponding benzylic chlorides 10 and alcohol derivatives,11 and provides a convenient method for the synthesis of sterically hindered aromatic amines with high regioselectivity. Therefore, we decided to optimize the reaction conditions to achieve higher yields. We first surveyed a number of palladium sources (5 mol %) in the model reaction of benzylic ammonium salt 1a with dialkylamine 2a in the presence of PPh3 (10 mol %) and NaOtBu (3 equiv) in tetrahydrofuran at 70 °C for 5 h (entries 2−9). Gratifyingly, the use of inexpensive Pd(OAc)2 afforded tertiary aromatic amine 3a in the highest yield, 86% (entry 6). Importantly, the corresponding benzylic substitution product, 4-(naphthalen-1-ylmethyl)morpholine, was not observed at all. Increasing the scale from 0.2 to 5 mmol gave a slightly lower

uaternary ammonium salts are readily accessible and have been widely employed in promoting aqueous solubility or in interacting with anionic partners.1 While the C−N bond cleavage of quaternary ammonium salts has been frequently demonstrated in a few well-known reactions such as the Hofmann elimination2 and the Stevens rearrangement,3 it is less often utilized in bond formation reactions with other molecules. Despite the huge challenge in the discrimination of different C−N bonds, significant progress has been made in the intermolecular bond formation reactions of quaternary aryl,4 benzylic,4h,k,5,6 allylic,6p,7 and propargylic8 ammonium salts, releasing electronically neutral tertiary amines as leaving groups. Although benzylic ammonium salts can be directly substituted by nucleophiles at the benzylic position,5 the use of transition metal catalysts significantly broadens the scope of their coupling partners (Scheme 1a). In the presence of palladium, rhodium, iridium, nickel, and copper catalysts, Scheme 1. C−N Bond Cleavage Reactions of Benzylic Ammonium Salts

Received: August 8, 2019

© XXXX American Chemical Society

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DOI: 10.1021/acs.orglett.9b02820 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters Table 1. Optimization of the Reaction Conditionsa

Scheme 2. Scope of Benzylic Ammonium Saltsa

entry

[Pd]

L

base

solvent

yield (%)b

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 29c 30d

PdCl2 Pd(PPh3)2Cl2 [Pd(allyl)Cl]2 Pd(PhCN)Cl2 Pd(COD)Cl2 Pd(OAc)2 Pd(OCOCF3)2 Pd(dba)2 Pd(PPh3)4 none Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2

PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 none PPh3 none (±)-BINAP dppf dppb dppp PCy3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3

NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu LiOtBu KOtBu NaOEt NaOH NaH K3PO4 Cs2CO3 DBU NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu

THF THF THF THF THF THF THF THF THF THF THF THF THF THF THF THF THF THF THF THF THF THF THF THF MTBE dioxane toluene hexane THF THF

70 86 25 78 75 86 80 81 85 0 0 trace 46 84 64 69 trace 84 0 0 82 0 0 0 46 0 45 26 79 60

a Reaction conditions: 1 (0.20 mmol), 2a (0.20 mmol), Pd(OAc)2 (5 mol %), PPh3 (10 mol %), NaOtBu (3 equiv), THF (1.0 mL), 70 °C, 5 h. Isolated yields are given. For the synthesis of 3r, N,N,N-trimethyl1-(thiophen-2-yl)methanaminium triflate (1r) was prepared in situ from N,N-dimethyl-1-(naphthalen-1-yl)-1-(thiophen-2-yl)methanamine and MeOTf.

a

Reaction conditions: 1a (0.20 mmol), 2a (0.20 mmol), [Pd] (5 mol %), L (10 mol %), base (3 equiv), solvent (1.0 mL), 70 °C, 5 h. b Isolated yield. c1a was replaced with N,N,N-trimethyl-1-(naphthalen1-yl)methanaminium chloride (1aa). d1a was replaced with N,N,Ntrimethyl-1-(naphthalen-1-yl)methanaminium iodide (1ab).

high regioselectivity (3a−h). The aromatic substitution reaction was successfully extended to a range of branched benzylic and dibenzylic ammonium triflates, in which only the naphthalene ring was substituted by dialkylamine 2a at the para position (3i−r).13 In all the above cases, the benzylic substitution products were not detected. Aromatic amine 3i was obtained in a low yield simply because competing Hofmann elimination of the benzylic ammonium triflate occurred to afford 1-vinylnaphthalene in 22% yield. Moreover, this method provides orthogonal reactivity to aryl halides (3c and 3o−q), which are amenable to further synthetic elaboration. We then surveyed the substrate scope for the amine partners in the aromatic substitution reaction of benzylic ammonium salt 1a (Scheme 3). The reaction proceeded well with both cyclic and acyclic secondary dialkylamines as well as Nmethylaniline under the standard conditions (3s−x). Notably, these reaction conditions selectively activate the benzylic C−N bond in the presence of benzylic C−O bonds (3v), highlighting the complementarity of benzylic ammonium salts to benzylic ethers. We next examined a number of primary amines. While the use of benzylamine as a nitrogen nucleophile led to the formation of secondary aromatic amine

yield (81%). The reaction failed to occur in the absence of either a palladium source or a phosphine ligand (entries 10 and 11). Next, we examined some other readily available phosphine ligands, bases,12 and solvents and failed to enhance the yield (entries 12−28). Finally, we investigated the counterion effect of the benzylic ammonium salt and obtained lower yields when replacing the triflate anion with a chloride anion or an iodide anion (entries 29 and 30). Under the optimized conditions (Table 1, entry 6), we observed a broad substrate scope for the benzylic ammonium triflates in the aromatic substitution reaction using dialkylamine 2a as a nitrogen nucleophile (Scheme 2). In addition to various substituted (naphthalen-1-yl)methylammonium triflates, (anthracen-9-yl)methyl and (phenanthren-1-yl)methylammonium triflates served as suitable substrates in the reaction to afford the corresponding sterically hindered tertiary aromatic amines in moderate to good yields with extremely B

DOI: 10.1021/acs.orglett.9b02820 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters Scheme 3. Scope of Secondary and Primary Aminesa

Scheme 4. Mechanistic Studies

a Reaction conditions: 1a (0.20 mmol), 2 (0.20 mmol), Pd(OAc)2 (5 mol %), PPh3 (10 mol %), NaOtBu (3 equiv), THF (1.0 mL), 70 °C, 5 h. Isolated yields are given. For the synthesis of 3w, NHMe2·HCl and NaOtBu (5 equiv) were used. The synthesis of 3y was run at 80 °C with Pd(PPh3)2Cl2 and o-phenylphenyl diphenylphosphane instead of Pd(OAc)2 and PPh3.

respectively. The structure of complex 5aaa was unambiguously confirmed by X-ray crystallography (CCDC 1907865), providing substantial evidence, for the first time, of the oxidative addition of a benzylic ammonium salt to a Pd(0) species through C−N bond cleavage. Both complexes 5aaa and 5aab participated in the coupling reaction with dialkylamine 2a to afford tertiary aromatic amine 3a albeit in unsatisfactory yields. Moreover, both of them were found to serve as effective catalysts in promoting the reaction between benzylic ammonium salt 1a and dialkylamine 2a. These results substantially support the intermediacy of π-benzylpalladium complexes in the aromatic substitution reaction of benzylic ammonium salts with amines. On the basis of the above experimental results and previous relevant reports,6g,q,10,15 we propose the following reaction pathway for the aromatic substitution reaction of benzylic ammonium salt 1a with dialkylamine 2a (Scheme 5). Oxidative addition of benzylic ammonium salt 1a to palladium(0) (PdLn), generated in situ from Pd(OAc)2 through reduction with the phosphine ligand or the amine substrate, affords trimethylamine and π-benzylpalladium complex 5a.6g Ligand substitution of complex 5a with dialkylamine 2a in the presence of a strong base affords π-benzylpalladium complex

3y in a low yield,14 the reaction with 1-adamantylamine, a very bulky primary aliphatic amine, gave a good yield (3z). In contrast, higher yields were achieved from the reaction with a range of primary aromatic amines, in which substitution was well tolerated at the para, meta, and ortho positions of the aromatic ring (3aa−ai). To gain insights into the reaction mechanism, we carried out several experiments to identify the intermediates generated in the aromatic substitution reaction of benzylic ammonium salts with amines (Scheme 4). After the reaction of benzylic ammonium salt 1k with dialkylamine 2a was performed under the standard conditions for 0.5 h, we quenched the reaction mixture and subsequently isolated γ-vinyl allylic amine 4k in 32% yield. Isomerization of this intermediate required the presence of NaOtBu and afforded aromatic amine 3k in 78% yield. Treatment of benzylic ammonium salt 1aa with a stoichiometric amount of Pd(PPh3)4 in tetrahydrofuran at room temperature permitted us to isolate two π-benzylpalladium complexes, 5aaa (having one phosphine ligand) and 5aab (having two phosphine ligands), in 38% and 32% yields, C

DOI: 10.1021/acs.orglett.9b02820 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters Scheme 5. Proposed Reaction Mechanism (L = PPh3, n = 1−4)

ORCID

Shi-Kai Tian: 0000-0002-2938-7013 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful for the financial support from the National Natural Science Foundation of China (21772182), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB20000000), and the Fundamental Research Funds for the Central Universities.

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6a.15 Then, complex 6a undergoes reductive elimination to afford γ-vinyl allylic amine 4a in a highly regioselective manner via intramolecular C−N bond coupling between the para carbon atom of the η3-exo-(1-naphthyl)methyl ligand and the nitrogen atom of the amide ligand (as shown in transition state 7a), and concurrently regenerates palladium(0) to continue the catalytic cycle.15 Finally, γ-vinyl allylic amine 4a participates in aromatization via isomerization under basic conditions to afford tertiary aromatic amine 3a.10 In summary, we have developed for the first time an aromatic substitution reaction of benzylic ammonium salts through palladium-catalyzed C−N bond cleavage. In the presence of 5 mol % Pd(OAc)2, 10 mol % PPh3, and 3 equiv of NaOtBu, a range of primary and secondary amines participated in the aromatic substitution reaction of benzylic ammonium salts to afford sterically hindered aromatic amines in moderate to excellent yields with extremely high regioselectivity. A plausible reaction mechanism was proposed according to the successful identification of π-benzylpalladium complexes and γ-vinyl allylic amines as key intermediates. This study paves the way for the use of benzylic ammonium salts in the aromatic substitution reactions.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b02820. Experimental procedures, characterization data, X-ray crystallographic data, and copies of NMR spectra (PDF) Accession Codes

CCDC 1907865 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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REFERENCES

(1) (a) Hashimoto, T.; Maruoka, K. Chem. Rev. 2007, 107, 5656− 5682. (b) Brière, J.-F.; Oudeyer, S.; Dalla, V.; Levacher, V. Chem. Soc. Rev. 2012, 41, 1696−1707. (c) Zhang, C.; Cui, F.; Zeng, G.-M.; Jiang, M.; Yang, Z.-Z.; Yu, Z.-G.; Zhu, M.-Y.; Shen, L.-Q. Sci. Total Environ. 2015, 518−519, 352−362. (d) Qian, D.; Sun, J. Chem. - Eur. J. 2019, 25, 3740−3751. (2) Cope, A. C.; Trumbull, E. R. Org. React. 1960, 11, 317−388. (3) (a) Markó, I. E. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3; pp 913−974. (b) BachAuthor Vitae, R.; HarthongAuthor Vitae, S.; Lacour, J. In Comprehensive Organic Synthesis II, 2nd ed.; Knochel, P., Molander, G. A., Eds.; Elsevier: Oxford, 2014; Vol. 3; pp 992−1037. (4) (a) Wenkert, E.; Han, A.-L.; Jenny, C.-J. J. Chem. Soc., Chem. Commun. 1988, 975−976. (b) Blakey, S. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 6046−6047. (c) Reeves, J. T.; Fandrick, D. R.; Tan, Z. L.; Song, J. J.; Lee, H.; Yee, N. K.; Senanayake, C. H. Org. Lett. 2010, 12, 4388−4391. (d) Xie, L.-G.; Wang, Z.-X. Angew. Chem., Int. Ed. 2011, 50, 4901−4904. (e) Zhang, X.-Q.; Wang, Z.-X. J. Org. Chem. 2012, 77, 3658−3663. (f) Guo, W.-J.; Wang, Z.-X. Tetrahedron 2013, 69, 9580−9585. (g) Zhang, X.-Q.; Wang, Z.-X. Org. Biomol. Chem. 2014, 12, 1448−1453. (h) Zhang, H.; Hagihara, S.; Itami, K. Chem. - Eur. J. 2015, 21, 16796−16800. (i) Zhu, F.; Tao, J.-L.; Wang, Z.-X. Org. Lett. 2015, 17, 4926−4929. (j) Wu, D.; Tao, J.-L.; Wang, Z.-X. Org. Chem. Front. 2015, 2, 265−273. (k) Hu, J.; Sun, H.; Cai, W.; Pu, X.; Zhang, Y.; Shi, Z. J. Org. Chem. 2016, 81, 14−24. (l) Wang, D.-Y.; Kawahata, M.; Yang, Z.-K.; Miyamoto, K.; Komagawa, S.; Yamaguchi, K.; Wang, C.; Uchiyama, M. S. Nat. Commun. 2016, 7, 12937. (m) Yi, Y.-Q.-Q.; Yang, W.-C.; Zhai, D.-D.; Zhang, X.-Y.; Li, S.-Q.; Guan, B.-T. Chem. Commun. 2016, 52, 10894−10897. (n) Ogawa, H.; Yang, Z.-K.; Minami, H.; Kojima, K.; Saito, T.; Wang, C.; Uchiyama, M. ACS Catal. 2017, 7, 3988−3994. (o) He, F.; Wang, Z.-X. Tetrahedron 2017, 73, 4450−4457. (5) (a) Snyder, H. R.; Eliel, E. L.; Charnahan, R. E. J. Am. Chem. Soc. 1951, 73, 970−973. (b) Brasen, W. R.; Hauser, C. R. J. Org. Chem. 1953, 18, 806−809. (c) Kellner, K.; Rothe, S.; Steyer, E. M.; Tzschach, A. Phosphorus Sulfur Relat. Elem. 1980, 8, 269−274. (d) Barton, D. H. R.; Fekih, A.; Lusinchi, X. Tetrahedron Lett. 1985, 26, 6197−6200. (e) Bordwell, F. G.; Hughes, D. L. J. Am. Chem. Soc. 1986, 108, 7300−7309. (f) Crozet, M. P.; Jentzer, O.; Vanelle, P. Tetrahedron Lett. 1987, 28, 5531−5534. (g) Kornblum, N.; Ackermann, P.; Manthey, J. W.; Musser, M. T.; Pinnick, H. W.; Singaram, S.; Wade, P. A. J. Org. Chem. 1988, 53, 1475−1481. (h) Stará, I. G.; Stary, I.; Závada, J. J. Org. Chem. 1992, 57, 6966− 6969. (i) Axelsson, O.; Peters, D. J. Heterocycl. Chem. 1997, 34, 461− 463. (j) Khalafi-Nezhad, A.; Zare, A.; Parhami, A.; Hasaninejad, A.; Moosavi Zare, A. R. J. Iran. Chem. Soc. 2008, 5, S40−S46. (k) Maraš, N.; Polanc, S.; Kočevar, M. Org. Biomol. Chem. 2012, 10, 1300−1310. (l) Gui, Y.; Tian, S.-K. Org. Lett. 2017, 19, 1554−1557. (m) Chen, Z.; Han, L.; Tian, S.-K. Org. Lett. 2017, 19, 5852−5855. (6) (a) Yi, P.; Zhuangyu, Z.; Hongwen, H. Synthesis 1995, 1995, 245−247. (b) de la Herrán, G.; Segura, A.; Csákÿ, A. G. Org. Lett. 2007, 9, 961−964. (c) Maity, P.; Shacklady-McAtee, D. M.; Yap, G. P. A.; Sirianni, E. R.; Watson, M. P. J. Am. Chem. Soc. 2013, 135, 280− 285. (d) Shacklady-McAtee, D. M.; Roberts, K. M.; Basch, C. H.;

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Corresponding Author

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DOI: 10.1021/acs.orglett.9b02820 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters Song, Y.-G.; Watson, M. P. Tetrahedron 2014, 70, 4257−4263. (e) Basch, C. H.; Cobb, K. M.; Watson, M. P. Org. Lett. 2016, 18, 136−139. (f) Moragas, T.; Gaydou, M.; Martin, R. Angew. Chem., Int. Ed. 2016, 55, 5053−5057. (g) Wang, T.; Yang, S.; Xu, S.; Han, C.; Guo, G.; Zhao, J. RSC Adv. 2017, 7, 15805−15808. (h) Liu, X.-Y.; Zhu, H.-B.; Shen, Y.-J.; Jiang, J.; Tu, T. Chin. Chem. Lett. 2017, 28, 350−353. (i) Türtscher, P. L.; Davis, H. J.; Phipps, R. J. Synthesis 2018, 50, 793−802. (j) Zhang, Z.; Wang, H.; Qiu, N.; Kong, Y.; Zeng, W.; Zhang, Y.; Zhao, J. J. Org. Chem. 2018, 83, 8710−8715. (k) Sasagawa, A.; Yamaguchi, M.; Ano, Y.; Chatani, N. Isr. J. Chem. 2017, 57, 964−967. (l) Yu, W.; Yang, S.; Xiong, F.; Fan, T.; Feng, Y.; Huang, Y.; Fu, J.; Wang, T. Org. Biomol. Chem. 2018, 16, 3099−3103. (m) Li, J.; Zheng, Z.; Xiao, T.; Xu, P.-F.; Wei, H. Asian J. Org. Chem. 2018, 7, 133−136. (n) Lu, F.; Chen, Z.; Li, Z.; Wang, X.; Peng, X.; Li, C.; Li, R.; Pei, H.; Wang, H.; Gao, M. Asian J. Org. Chem. 2018, 7, 141−144. (o) Jiang, W.; Li, N.; Zhou, L.; Zeng, Q. ACS Catal. 2018, 8, 9899−9906. (p) Liao, L.-L.; Cao, G.-M.; Ye, J.-H.; Sun, G.-Q.; Zhou, W.-J.; Gui, Y.-Y.; Yan, S.-S.; Shen, G.; Yu, D.-G. J. Am. Chem. Soc. 2018, 140, 17338−17342. (q) Wang, T.; Guo, J.; Wang, X.; Guo, H.; Jia, D.; Wang, H.; Liu, L. RSC Adv. 2019, 9, 5738−5741. (r) Yang, D.-T.; Zhu, M.; Schiffer, Z. J.; Williams, K.; Song, X.; Liu, X.; Manthiram, K. ACS Catal. 2019, 9, 4699−4705. (7) (a) Dressaire, G.; Langlois, Y. Tetrahedron Lett. 1980, 21, 67−70. (b) Langlois, Y.; Van Bac, N.; Fall, Y. Tetrahedron Lett. 1985, 26, 1009−1012. (c) Van Bac, N.; Fall, Y.; Langlois, Y. Tetrahedron Lett. 1986, 27, 841−844. (d) Hosomi, A.; Hoashi, K.; Tominaga, Y. J. J. Org. Chem. 1987, 52, 2947−2948. (e) Gupton, J. T.; Layman, W. J. J. Org. Chem. 1987, 52, 3683−3686. (f) Hosomi, A.; Hoashi, K.; Kohra, S.; Tominaga, Y.; Otaka, K.; Sakurai, H. J. Chem. Soc., Chem. Commun. 1987, 570−571. (g) Doi, T.; Yanagisawa, A.; Miyazawa, M.; Yamamoto, K. Tetrahedron: Asymmetry 1995, 6, 389−392. (h) Raskatov, J. A.; Jäkel, M.; Straub, B. F.; Rominger, F.; Helmchen, G. Chem. Eur. J. 2012, 18, 14314−14328. (8) (a) Iwai, I.; Hiraoka, T. Chem. Pharm. Bull. 1962, 10, 81−86. (b) Murai, T.; Fukushima, K.; Mutoh, Y. Org. Lett. 2007, 9, 5295− 5298. (c) Guisán-Ceinos, M.; Martín-Heras, V.; Tortosa, M. J. Am. Chem. Soc. 2017, 139, 8448−8451. (d) Ma, S.; Liu, Q.; Tang, X.; Cai, Y. Asian J. Org. Chem. 2017, 6, 1209−1212. (e) Guisán-Ceinos, M.; Martín-Heras, V.; Soler-Yanes, R.; Cárdenas, D. J.; Tortosa, M. Chem. Commun. 2018, 54, 8343−8346. (f) Zhang, L.; Zhang, Z.-J.; Xiao, J.Y.; Song, J. Org. Lett. 2018, 20, 5519−5522. (9) (a) Zhang, J.; Chen, Z.-X.; Du, T.; Li, B.; Gu, Y.; Tian, S.-K. Org. Lett. 2016, 18, 4872−4875. (b) Zhou, M.-G.; Dai, R.-H.; Tian, S.-K. Chem. Commun. 2018, 54, 6036−6039. (c) Xu, Y.-N.; Tian, S.-K. Tetrahedron 2019, 75, 1632−1638. (d) Jin, Y.-X.; Yu, B.-K.; Qin, S.P.; Tian, S.-K. Chem. - Eur. J. 2019, 25, 5169−5172. (10) (a) Bao, M.; Nakamura, H.; Yamamoto, Y. J. Am. Chem. Soc. 2001, 123, 759−760. (b) Peng, B.; Feng, X.; Zhang, X.; Ji, L.; Bao, M. Tetrahedron 2010, 66, 6013−6018. (c) Zhang, S.; Wang, Y.; Feng, X.; Bao, M. J. Am. Chem. Soc. 2012, 134, 5492−5495. (d) Zhang, S.; Yu, X.; Feng, X.; Yamamoto, Y.; Bao, M. Chem. Commun. 2015, 51, 3842−3845. (e) Zhang, S.; Cai, J.; Yamamoto, Y.; Bao, M. J. Org. Chem. 2017, 82, 5974−5980. (f) Zhang, S.; Ullah, A.; Yamamoto, Y.; Bao, M. Adv. Synth. Catal. 2017, 359, 2723−2728. (11) (a) Ueno, S.; Komiya, S.; Tanaka, T.; Kuwano, R. Org. Lett. 2012, 14, 338−341. (b) Komatsuda, M.; Muto, K.; Yamaguchi, J. Org. Lett. 2018, 20, 4354−4357. (12) A small amount of the benzylic substitution product, 4(naphthalen-1-ylmethyl)morpholine, was observed when using the bases shown in Table 1 except NaOtBu, KOtBu, and NaH. (13) The aromatic substitution reaction was not observed with the phenyl ring (3k and 3q) and the thiophenyl ring (3r). Moreover, we did not observe the reaction of PhCH2NMe3OTf (1s) with dialkylamine 2a under the standard conditions. (14) Under the standard conditions amine 3y was obtained in 22% yield and 1-methylnaphthalene was isolated as an undesired product in 53% yield. (15) For density functional theory calculations, see: Xie, H.; Zhang, H.; Lin, Z. Organometallics 2013, 32, 2336−2343. E

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