Photoredox-Catalyzed Diamidation and Oxidative Amidation of

Letter pubs.acs.org/OrgLett

Photoredox-Catalyzed Diamidation and Oxidative Amidation of Alkenes: Solvent-Enabled Synthesis of 1,2-Diamides and α‑Amino Ketones Qixue Qin,† Yue-Yue Han,† Yan-Yan Jiao, Yanyan He, and Shouyun Yu* State Key Laboratory of Analytical Chemistry for Life Science, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China S Supporting Information *

ABSTRACT: Photoredox-catalyzed difunctionalizations of alkenes with O-acyl hydroxylamine derivatives are described. The solvent tunes the outcome of these reactions. Diamidation and oxidative amidation of alkenes can be achieved in CH3CN and DMSO, respectively. A variety of 1,2-diamidates and α-amino ketones bearing many functional groups are prepared using Ir(ppy)3 as the photocatalyst under visible light irradiation.

V

was reported.16v Inspired by these works and our continuous interest in visible-light-mediated N-centered radical chemistry,15 we envisioned that diamidation and oxidative amidation of alkenes could be achieved under similar photoredox conditions. As demonstrated in Scheme 1, photoreductive cleavage of an O-

icinal difunctionalization of alkenes is a powerful tool to create complex molecular architectures and offers an attractive route to numerous classes of N-containing molecules.1 Amination or amidation of alkenes offers the most attractive route to numerous classes of N-containing molecules.2 Generally, C−N and C−X (X = H, O, N, halide, etc.) bonds can be introduced through direct functionalization of alkenes, including hydroamination,3 aminohydroxylation,4 diamination,5 and haloamination6 reactions. Despite the significance of these achievements, different sets of starting materials must be selected specifically and reaction conditions have to be optimized for each of these processes. Vicinal diamines and α-amino ketones are important motifs that are widely found in natural products and physiologically active molecules,7 such as levamisole,8 Sch 425078,9 Tamiflu,10 and MK-320711 (Figure 1). Diamination12 and oxidative amination13 of alkenes are direct and attractive methods to access these structures. Recently, it was found that N-centered radicals are widely involved in C−N bond formation under photoredox conditions.14−16 Intermolecular aminohydroxylation of alkenes enabled by photoredox catalysis16d and synthesis of imidazolines and oxazolidines through nitrogen-centered radicals

Scheme 1. Rationale for the Solvent-Enabled Synthesis of 1,2Diamides and α-Amino Ketones

acyl hydroxylamine derivative could give a N-centered radical I, which could be trapped by an alkene to generate alkyl radical intermediate II. Oxidation of radical II could produce carbocation III. The fate of cation III could be determined by the solvent that is used: In CH3CN, III would be trapped by the solvent to generate a diamidation product IV through a Ritter-type reaction17 followed by acyl migration. If DMSO was used as the solvent, an α-amino ketone V could be generated via a Kornblum oxidation process.18 Herein, we report the solvent-enabled selective synthesis of 1,2-diamides and α-amino ketones by Figure 1. Pharmaceuticals incorporating the vicinal diamines and αamino ketones. © 2017 American Chemical Society

Received: April 14, 2017 Published: May 16, 2017 2909

DOI: 10.1021/acs.orglett.7b01145 Org. Lett. 2017, 19, 2909−2912

Letter

Organic Letters photoredox-catalyzed difunctionalization of alkenes with O-acyl hydroxylamine derivatives. We first investigated the photoredox-catalyzed diamidation of styrenes with O-acyl hydroxylamine derivatives in CH3CN. Given that the protecting group on the N atom of hydroxylamine and the leaving propensity of an O-acyl group are crucial to the generation of the N-centered radical,15,19 a series of N-centered radical precursors were prepared and evaluated under photoredox conditions (Scheme 2). With Ir(ppy)3 as the photocatalyst

afford the corresponding diamidation products 4b−4i in moderate to good yields (47−68%). The ortho- and metasubstituted styrenes were also suitable substrates in this transformation, giving products 4j−4l in 48−69% yields. Disubstituted styrenes worked well to provide the diamidation products 4m and 4n in 76 and 64% yields, respectively. When 1and 2-vinylnaphthalene were used in this reaction, 4o and 4p were isolated in 52 and 54% yields, respectively. N-Methyl hydroxylamine derivative 2h was more efficient than 2d, which reacted with para-methylstyrene (1a) to give the corresponding diamidation product 4q in 80% yield. A biologically important estrone-derived alkene went through this transformation smoothly with 2d and 2h to afford 4r and 4s in 44 and 66% yields, respectively. Linear 1,2-disubstituted olefins could not undergo this reaction. Having achieved success in the photoredox-catalyzed diamidation of styrenes, we next explored the possibility of photoredoxcatalyzed oxidative amidation of styrenes using this strategy. After a quick screening (Scheme 4; for a full condition screening, see the

Scheme 2. Screening of N-Centered Radical Precursors for Diamidation

Scheme 4. Scope of Synthesis of α-Amino Ketonesa under visible light irradiation and 2,2,2-trichloroethyl 4cyanobenzoyloxycarbamate (2d) as the N-centered radical precursor, the corresponding diamidation product was obtained in 71% yield (for more detailed reaction screening, see the Supporting Information (SI)). The protecting groups on the N atom were also examined. When Boc (2f) and Cbz (2g) groups were used instead of the 2,2,2-trichloroethoxycarbonyl (Troc) group, no desired products were observed. We then investigated the scope and limitations of our photoredox-catalyzed diamidation of alkenes (Scheme 3). Styrenes bearing electron-withdrawing, -neutral, and -donating substituents at the para positions reacted smoothly with 2d to Scheme 3. Scope of 1,2-Diamidation of Styrenesa

a Reaction conditions: 1 (0.1 mmol, 1 equiv), 2c, 2i, or 2j (0.2 mmol, 2 equiv), and Ir(ppy)3 (0.001 mmol, 1 mol %) in DMSO (3 mL) were irradiated by white LED strips for 3−12 h. Isolated yield. b3.5 mmol scale.

SI), the photoredox-catalyzed oxidative amidation of styrene 1e was achieved in DMSO using Ir(ppy)3 as the photocatalyst irradiated by white LEDS, with hydroxylamine derivative 2c as the best N-centered radical precursor with 81% yield for 5c. Comparable yield (78%, 0.93 g) of 5c was obtained when the reaction was scaled up to 3.5 mmol scale. With the optimized conditions in hand, we next prepared a variety of α-amino ketones using this method (Scheme 4). Styrenes with various substituents reacted smoothly with 2c to generate the corresponding α-amino ketones 5a−5k in 47−81% yields. Naphthalene- and thiophenederived alkenes went through this reaction smoothly to give the desired α-amino ketones 5l−5n in 41−66% yields. Indene could

a Reaction conditions: solution of 1 (0.1 mmol, 1 equiv), 2d or 2h (0.2 mmol, 2 equiv), and Ir(ppy)3 (0.001 mmol, 1 mol %) in CH3CN (2 mL) was irradiated by white LED strips for 3−12 h. Isolated yield.

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DOI: 10.1021/acs.orglett.7b01145 Org. Lett. 2017, 19, 2909−2912

Letter

Organic Letters react with 2c to give the α-amino ketone 5o in 46% yield. Notably, N-methyl hydroxylamine derivative 2i was a more suitable Ncentered radical precursor and could react with styrenes with excellent yields (96% for 5p and 92% for 5q). While N-phenyl hydroxylamine derivative 2j was less efficient and afforded the corresponding α-amino ketone 5r with decreased yield (38%). Modified biologically valuable molecules, such as estrone and amino acid, were also feasible. Estrone-derived amino ketones 5s and 5t and phenylalanine-derived amino ketone 5u could be prepared in reasonable yields using this method. To better understand the mechanism of this photoredoxcatalyzed difunctionalization of alkenes, a series of control experiments were performed (Scheme 5). The radical nature of Scheme 5. Control Experiments

Figure 2. Proposed mechanism.

then trapped by styrene 1 to produce alkyl radical intermediate 10, which is oxidized to carbocation 11 by IrIV with the regeneration of photocatalyst IrIII. At this stage, the fate of 11 is determined by the solvent. In CH3CN, 11 is trapped by the solvent to give the nitrilium ion 12 through a Ritter-type reaction.17 Attack by the 9 followed by acyl migration then affords the final diamidation product 4. When DMSO is used as the solvent, 11 can also be attacked by the solvent to afford the alkoxysulfonium intermediate 14, which undergoes a Kornblum oxidation process18 to provide the α-amino ketone 5. The possibility of radical chain propagation (radical 10 undergoing SET with 2, inducing reductive cleavage to generate radicals 8, and feeding a radical chain) cannot be ruled out at this stage. In conclusion, we developed a photoredox-catalyzed diamidation and oxidative amidation of alkenes with O-acyl hydroxylamine derivatives. In this process, N-centered radicals are generated from O-acyl hydroxylamine derivatives under visible light irradiation, and the outcome of this reaction is determined by the solvent. Diamidation and oxidative amidation of alkenes can be achieved in CH3CN and DMSO, respectively. We showed that a variety of 1,2-diamidates and α-amino ketones bearing different functional groups can be prepared using this strategy. Our current research is focusing on the synthesis and modification of biologically important N-containing molecules with this method.

these reactions was supported by TEMPO-trapping and radical clock experiments. Desired diamidation reaction of alkene 1a with 2d in CH3CN was totally shut down in the presence of radical scavenger TEMPO. Instead, TEMPO-trapped product 6 was isolated in 17% yield (Scheme 5a). When probe molecule 1x was subjected to the standard oxidative amidation conditions, the ring-opened product 7 was obtained in 41% yield (Scheme 5b). When the diamidation reaction of alkene 1a was studied with 2d in CD3CN, deuterated product 4t was produced in 60% yield. This experiment suggests that the acetyl group of the diamidation product derives from the CH3CN (Scheme 5c). We next tried to determine the source of oxygen in the oxidative amidation reactions via 18O-labeling experiments (Scheme 5d). When H218O was introduced into a reaction mixture of 1a and 2c in DMSO, 16O-5b was isolated (61% yield) without any 18O-labeled product. This reaction proceeded smoothly even in degassed DMSO and under nitrogen gas protection (58% yield). These experiments exclude the possibility that water and oxygen serve as the oxygen sources, which supports the idea that DMSO is the sole oxidant.20 Based on these observations, a plausible mechanism is proposed (Figure 2). Photoreductive cleavage of 2 by the excited-state photocatalyst IrIII* gives radical 8 and carboxylate anion 9 with the generation of IrIV. The N-centered radical 8 is

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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.7b01145. Experimental procedures and characterization data (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Shouyun Yu: 0000-0003-4292-4714 Author Contributions †

Q.Q. and Y.-Y.H. contributed equally.

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DOI: 10.1021/acs.orglett.7b01145 Org. Lett. 2017, 19, 2909−2912

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Organic Letters Notes

12, 4051. (f) Chen, J.-R.; Hu, X.-Q.; Lu, L.-Q.; Xiao, W.-J. Chem. Soc. Rev. 2016, 45, 2044. (g) Xiong, T.; Zhang, Q. Chem. Soc. Rev. 2016, 45, 3069. (15) (a) Jiang, H.; An, X.; Tong, K.; Zheng, T.; Zhang, Y.; Yu, S. Angew. Chem., Int. Ed. 2015, 54, 4055. (b) An, X.-D.; Yu, S. Org. Lett. 2015, 17, 2692. (c) Qin, Q.; Yu, S. Org. Lett. 2015, 17, 1894. (d) Qin, Q.; Yu, S. Org. Lett. 2014, 16, 3504. (e) Tong, K.; Liu, X.; Zhang, Y.; Yu, S. Chem. - Eur. J. 2016, 22, 15669. (f) Qin, Q.; Ren, D.; Yu, S. Org. Biomol. Chem. 2015, 13, 10295. (16) (a) Maity, S.; Zheng, N. Angew. Chem., Int. Ed. 2012, 51, 9562. (b) Cecere, G.; König, C. M.; Alleva, J. L.; MacMillan, D. W. C. J. Am. Chem. Soc. 2013, 135, 11521. (c) MartIń ez, C.; Muñiz, K. Angew. Chem., Int. Ed. 2015, 54, 8287. (d) Miyazawa, K.; Koike, T.; Akita, M. Chem. Eur. J. 2015, 21, 11677. (e) Pandey, G.; Laha, R. Angew. Chem., Int. Ed. 2015, 54, 14875. (f) O’Broin, C. Q.; Fernández, P.; MartIń ez, C.; Muñiz, K. Org. Lett. 2016, 18, 436. (g) Davies, J.; Booth, S. G.; Essafi, S.; Dryfe, R. W. A.; Leonori, D. Angew. Chem., Int. Ed. 2015, 54, 14017. (h) Hu, X.-Q.; Chen, J.-R.; Wei, Q.; Liu, F.-L.; Deng, Q.-H.; Beauchemin, A. M.; Xiao, W.-J. Angew. Chem., Int. Ed. 2014, 53, 12163. (i) Hu, X.-Q.; Qi, X.; Chen, J.-R.; Zhao, Q.-Q.; Wei, Q.; Lan, Y.; Xiao, W.-J. Nat. Commun. 2016, 7, 11188. (j) Miller, D. C.; Choi, G. J.; Orbe, H. S.; Knowles, R. R. J. Am. Chem. Soc. 2015, 137, 13492. (k) Allen, L. J.; Cabrera, P. J.; Lee, M.; Sanford, M. S. J. J. Am. Chem. Soc. 2014, 136, 5607. (l) Davies, J.; Svejstrup, T. D.; Fernandez Reina, D.; Sheikh, N. S.; Leonori, D. J. Am. Chem. Soc. 2016, 138, 8092. (m) Brachet, E.; Ghosh, T.; Ghosh, I.; König, B. Chem. Sci. 2015, 6, 987. (n) Kim, H.; Kim, T.; Lee, D. G.; Roh, S. W.; Lee, C. Chem. Commun. 2014, 50, 9273. (o) Song, L.; Zhang, L.; Luo, S.; Cheng, J.-P. Chem. - Eur. J. 2014, 20, 14231. (p) Xu, F.; Zhu, L.; Zhu, S.; Yan, X.; Xu, H.-C. Chem. - Eur. J. 2014, 20, 12740. (q) Zhu, L.; Xiong, P.; Mao, Z.-Y.; Wang, Y.-H.; Yan, X.; Lu, X.; Xu, H.-C. Angew. Chem., Int. Ed. 2016, 55, 2226. (r) Greulich, T. W.; Daniliuc, C. G.; Studer, A. Org. Lett. 2015, 17, 254. (s) Zhao, Y.; Huang, B.; Yang, C.; Xia, W. Org. Lett. 2016, 18, 3326. (t) Ren, X.; Guo, Q. H.; Chen, J. H.; Xie, H. J.; Xu, Q.; Lu, Z. Chem. - Eur. J. 2016, 22, 18695. (u) Liu, J. Z.; Wu, K.; Shen, T.; Liang, Y. J.; Zou, M. C.; Zhu, Y. C.; Li, X. W.; Li, X. Y.; Jiao, N. Chem. - Eur. J. 2017, 23, 563. (v) Chen, J.-Q.; Yu, W.-L.; Wei, Y.-L.; Li, T.-H.; Xu, P.-F. J. Org. Chem. 2017, 82, 243. (w) Zhao, Q.-Q.; Hu, X.-Q.; Yang, M.-N.; Chen, J.R.; Xiao, W.-J. Chem. Commun. 2016, 52, 12749. (x) Yu, X.-Y.; Zhou, F.; Chen, J.-R.; Xiao, W.-J. Huaxue Xuebao 2017, 75, 86. (17) (a) Ritter, J. J.; Minieri, P. P. J. Am. Chem. Soc. 1948, 70, 4045. (b) Ritter, J. J.; Kalish, J. J. Am. Chem. Soc. 1948, 70, 4048. (c) Prasad Hari, D.; Hering, T.; König, B. Angew. Chem., Int. Ed. 2014, 53, 725. (18) (a) Kornblum, N.; Powers, J. W.; Anderson, G. J.; Jones, W. J.; Larson, H. O.; Levand, O.; Weaver, W. M. J. Am. Chem. Soc. 1957, 79, 6562. (b) Liang, Y.-F.; Wu, K.; Song, S.; Li, X.; Huang, X.; Jiao, N. Org. Lett. 2015, 17, 876. (c) Tomita, R.; Yasu, Y.; Koike, T.; Akita, M. Angew. Chem., Int. Ed. 2014, 53, 7144. (19) (a) Lu, D. F.; Zhu, C. L.; Jia, Z. X.; Xu, H. J. Am. Chem. Soc. 2014, 136, 13186. (b) Liu, G. S.; Zhang, Y. Q.; Yuan, Y. A.; Xu, H. J. Am. Chem. Soc. 2013, 135, 3343. (c) Zhu, C. L.; Lu, D. F.; Sears, J. D.; Jia, Z. X.; Xu, H. Synthesis 2016, 48, 3031. (20) When reaction of 1a and 2c was conducted in 18O-labeled DMSO, a complicated mixture was generated.

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS National Natural Science Foundation of China (21472084, 21672098, and 81421091) is acknowledged for financial support. REFERENCES

(1) (a) Romero, R. M.; Woste, T. H.; Muñiz, K. Chem. - Asian J. 2014, 9, 972. (b) Yin, G. Y.; Mu, X.; Liu, G. S. Acc. Chem. Res. 2016, 49, 2413. (2) Muller, T. E.; Beller, M. Chem. Rev. 1998, 98, 675. (3) (a) Muller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795. (b) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673. (c) Beller, M.; Seayad, J.; Tillack, A.; Jiao, H. J. Angew. Chem., Int. Ed. 2004, 43, 3368. (d) Hultzsch, K. C. Adv. Synth. Catal. 2005, 347, 367. (e) Crozet, D.; Urrutigoity, M.; Kalck, P. ChemCatChem 2011, 3, 1102. (4) (a) Donohoe, T. J.; Callens, C. K. A.; Flores, A.; Lacy, A. R.; Rathi, A. H. Chem. - Eur. J. 2011, 17, 58. (b) O'Brien, P. Angew. Chem., Int. Ed. 1999, 38, 326. (c) Muñiz, K. Chem. Soc. Rev. 2004, 33, 166. (5) (a) Zhu, Y. G.; Cornwall, R. G.; Du, H. F.; Zhao, B. G.; Shi, Y. A. Acc. Chem. Res. 2014, 47, 3665. (b) De Jong, S.; Nosal, D. G.; Wardrop, D. J. Tetrahedron 2012, 68, 4067. (c) Cardona, F.; Goti, A. Nat. Chem. 2009, 1, 269. (d) Muñiz, K.; Martínez, C. J. Org. Chem. 2013, 78, 2168. (e) Beccalli, E. M.; Broggini, G.; Gazzola, S.; Mazza, A. Org. Biomol. Chem. 2014, 12, 6767. (f) Zhang, H.; Pu, W.; Xiong, T.; Li, Y.; Zhou, X.; Sun, K.; Liu, Q.; Zhang, Q. Angew. Chem., Int. Ed. 2013, 52, 2529. (6) (a) Li, G. G.; Kotti, S. R. S. S.; Timmons, C. Eur. J. Org. Chem. 2007, 2007, 2745. (b) Chemler, S. R.; Bovino, M. T. ACS Catal. 2013, 3, 1076. (7) (a) Lucet, D.; Le Gall, T.; Mioskowski, C. Angew. Chem., Int. Ed. 1998, 37, 2580. (b) Saibabu Kotti, S. R. S.; Timmons, C.; Li, G. G. Chem. Biol. Drug Des. 2006, 67, 101. (8) Moertel, C. G.; Fleming, T. R.; Macdonald, J. S.; Haller, D. G.; Laurie, J. A.; Goodman, P. J.; Ungerleider, J. S.; Emerson, W. A.; Tormey, D. C.; Glick, J. H.; Veeder, M. H.; Mailliard, J. A. N. Engl. J. Med. 1990, 322, 352. (9) (a) Shue, H.-J.; Chen, X.; Shih, N.-Y.; Blythin, D. J.; Paliwal, S.; Lin, L.; Gu, D.; Schwerdt, J. H.; Shah, S.; Reichard, G. A.; Piwinski, J. J.; Duffy, R. A.; Lachowicz, J. E.; Coffin, V. L.; Liu, F.; Nomeir, A. A.; Morgan, C. A.; Varty, G. B. Bioorg. Med. Chem. Lett. 2005, 15, 3896. (b) Shue, H.-J.; Chen, X.; Schwerdt, J. H.; Paliwal, S.; Blythin, D. J.; Lin, L.; Gu, D.; Wang, C.; Reichard, G. A.; Wang, H.; Piwinski, J. J.; Duffy, R. A.; Lachowicz, J. E.; Coffin, V. L.; Nomeir, A. A.; Morgan, C. A.; Varty, G. B.; Shih, N.-Y. Bioorg. Med. Chem. Lett. 2006, 16, 1065. (10) (a) Hernan, M. A.; Lipsitch, M. Clin. Infect. Dis. 2011, 53, 277. (b) Butler, D. Nature 2014, 508, 439. (11) Bell, I. M.; Gallicchio, S. N.; Wood, M. R.; Quigley, A. G.; Stump, C. A.; Zartman, C. B.; Fay, J. F.; Li, C. C.; Lynch, J. J.; Moore, E. L.; Mosser, S. D.; Prueksaritanont, T.; Regan, C. P.; Roller, S.; Salvatore, C. A.; Kane, S. A.; Vacca, J. P.; Selnick, H. G. ACS Med. Chem. Lett. 2010, 1, 24. (12) (a) Chong, A. O.; Oshima, K.; Sharpless, K. B. J. Am. Chem. Soc. 1977, 99, 3420. (b) Du, H.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 762. (c) Du, H.; Yuan, W.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 7496. (d) Muñiz, K.; Hövelmann, C. H.; Streuff, J. J. Am. Chem. Soc. 2008, 130, 763. (e) Iglesias, Á .; Pérez, E. G.; Muñiz, K. Angew. Chem., Int. Ed. 2010, 49, 8109. (f) Zabawa, T. P.; Kasi, D.; Chemler, S. R. J. Am. Chem. Soc. 2005, 127, 11250. (g) Zabawa, T. P.; Chemler, S. R. Org. Lett. 2007, 9, 2035. (h) Wang, Y.-F.; Zhu, X.; Chiba, S. J. Am. Chem. Soc. 2012, 134, 3679. (i) Shen, K.; Wang, Q. Chem. Sci. 2015, 6, 4279. (j) Liu, R.-H.; Wei, D.; Han, B.; Yu, W. ACS Catal. 2016, 6, 6525. (k) De Haro, T.; Nevado, C. Angew. Chem., Int. Ed. 2011, 50, 906. (l) Danneman, M. W.; Hong, K. B.; Johnston, J. N. Org. Lett. 2015, 17, 2558. (13) (a) Minisci, F.; Galli, R. Tetrahedron Lett. 1964, 5, 3197. (b) Shinde, M. H.; Kshirsagar, U. A. Org. Biomol. Chem. 2016, 14, 858. (14) (a) Fallis, A. G.; Brinza, I. M. Tetrahedron 1997, 53, 17543. (b) Zard, S. Z. Chem. Soc. Rev. 2008, 37, 1603. (c) Minozzi, M.; Nanni, D.; Spagnolo, P. Chem. - Eur. J. 2009, 15, 7830. (d) Maity, S.; Zheng, N. Synlett 2012, 23, 1851. (e) Chiba, S.; Chen, H. Org. Biomol. Chem. 2014, 2912

DOI: 10.1021/acs.orglett.7b01145 Org. Lett. 2017, 19, 2909−2912