Letter pubs.acs.org/OrgLett
Synthesis of 4‑Isoxazolines via Visible-Light Photoredox-Catalyzed [3 + 2] Cycloaddition of Oxaziridines with Alkynes Gwang Seok Jang, Junggeun Lee, Jungseok Seo, and Sang Kook Woo* Department of Chemistry, University of Ulsan, 93 Daehak-Ro, Nam-Gu, Ulsan 44610, Korea S Supporting Information *
ABSTRACT: A method for [3 + 2] cycloaddition of oxaziridines with alkynes to form 4-isoxazolines via visible-light photoredox catalysis is described. This method is a greener, atom-economical reaction that tolerates various functional groups and provides good to excellent yield. Moreover, the cyclization products can be conveniently converted into tetrasubstituted allylic alcohols and enamines. A mechanistic study suggests that the reaction involves photoredox-catalyzed in situ generation of a nitrone from the oxaziridine by SET.
1,3-Dipolar cycloadditions have long been powerful synthetic transformations in organic chemistry because they provide efficient and atom-economical methods for construction of various five-membered heterocycles.1 Nitrones are widely used 1,3-dipoles in [3 + 2] cycloadditions as they generate useful products, isoxazolidines or 4-isoxazolines, which are not only important scaffolds for various biologically active compounds but are also precursors of broadly useful building blocks. Traditionally, nitrones have been prepared by condensation of aldehydes or ketones with N-hydroxylamines2 and via oxidation of amines, N-hydroxylamines, and imines.3 However, traditional methods often give poor yields and require harsh reaction conditions, such as high temperature or a strong oxidant, and also display problems in the handling of unstable nitrones.4 Recently, in situ generation of nitrones from N-hydroxy amines or N-hydroxyl-αamido sulfones has been developed to avoid an isolation step for the nitrone.5 Despite advances with these synthetic methods, improvement is still desirable for a mild, efficient synthetic protocol. Visible-light-mediated photoredox catalysis is an emerging research area in organic synthesis since visible light provides an inexpensive, infinite, and clean energy source. Many researchers have focused on applying visible photoredox catalysis to organic transformations.6 Recently, [3 + 2] cycloaddition reactions using in situ generated 1,3-dipoles via visible-light photoredox catalysis have been reported for the synthesis of five-membered heterocycles.7 In particular, Rueping and co-workers developed an in situ generation of nitrones from hydroxyl amines leading to [3 + 2] cycloadditions with alkenes to deliver isoxazolidines.7d 4-Isoxazolines are important five-membered heterocycles found in many biologically active natural products and pharmaceutical compounds.8 Through cleavage of the weak N−O bond, 4-isoxazolines serve as precursors to 1,3-amino alcohols, β-amino acids, β-lactams, and a variety of Nheterocycles. A common synthetic method for the preparation of 4-isoxazolines is [3 + 2] cycloaddition of nitrones with alkynes or allenes.5a,d,9 Recently, an intramolecular cyclization of propargylic N-hydroxylamines has been developed.10 © 2017 American Chemical Society
Three-membered heterocycles, which have high ring strain, are reactive intermediates in organic synthesis. In particular, they have been developed as precursors of 1,3-dipoles or radical ions in [3 + 2] cycloaddition reactions through generation by thermal, photo, and transition-metal catalysis. The ring-opening of 2Hazirine has been reported through visible-light-mediated photoredox-catalyzed single-electron transfer (SET) (Scheme 1,a). Scheme 1. Cycloadditions with Three-Membered Heterocycles Using Visible Light Photoredox Catalysis
Xiao and co-workers have developed the synthesis of pyrroles and oxazoles from 2H-azirine by a visible photoredox-catalyzed formal [3 + 2] cycloaddition reaction.7e,f Wang and co-workers reported the three-component cyclization of 2H-azirines, alkynyl bromides, and oxygen via visible light-mediated photoredox catalysis.7g Based on these previous reports on photoredoxcatalyzed functionalization of three-membered heterocycles, we envisioned generation of nitrones from oxaziridines by visiblelight photoredox catalysis for use as 1,3-dipoles in [3 + 2] cycloadditions. The organic sensitized photolysis of oxaziridines has been studied;11 however, to the best of our knowledge, Received: October 29, 2017 Published: November 20, 2017 6448
DOI: 10.1021/acs.orglett.7b03369 Org. Lett. 2017, 19, 6448−6451
Letter
Organic Letters Scheme 2. Substrate Scope of Various Alkynesa
visible-light-mediated photolysis of oxaziridines and the subsequent cyclization reaction have not been described. Herein, we present a highly efficient visible light-mediated photoredoxcatalyzed [3 + 2] cycloaddition of oxaziridines with alkynes to form 4-isoxazolines in a greener and step atom-economical method (Scheme 1,b). Initially, we explored the [3 + 2] cycloaddition reaction of oxaziridine 1a with dimethyl acetylenedicarboxylate (DMAD) 2a in ethyl acetate using 5 mol % visible-light photoredox catalysts under irradiation with 6 W blue LEDs. In a photoredox catalyst screening, the cycloaddition of oxaziridine 1a with DMAD 2a in the presence of Fukuzumi acridinium salt (Acr+-Mes) for 24 h gave the desired 4-isoxazoline 3a in 55% yield (Table 1, entry 5), Table 1. Optimization of the Reaction Conditionsa
a
Reaction conditions as given in Table 1, entry 16; reported yields are for isolated material. b2a (1.0 mmol), Acr+-Mes (2 mol %), EtOAc (0.5 M) was used as solvent, without H2O, 60 °C. See the Supporting Information for details. entry
2a (equiv)
1
5.0
2
5.0
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18c
5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 3.0 2.0 2.0 2.0
cat. (mol %) fac-Ir(ppy)3 (5) Ru(bpy)3Cl2 (5) rose bengal (5) eosin Y (5) Acr+-Mes (5) Acr+-Mes (5) Acr+-Mes (5) Acr+-Mes (5) Acr+-Mes (5) Acr+-Mes (5) Acr+-Mes (5) Acr+-Mes (5) Acr+-Mes (3) Acr+-Mes (1) Acr+-Mes (1) Acr+-Mes (1) Acr+-Mes (1)
additive (equiv)
H2O (2.5) H2O (2.5) H2O (2.5) H2O (2.5) H2O (2.5) H2O (2.5) H2O (2.5)
solvent (M)
yieldb (%)
EtOAc (0.2)
nd
EtOAc (0.2)
trace
EtOAc (0.2) EtOAc (0.2) EtOAc (0.2) CH2Cl2 (0.2) toluene (0.2) CH3NO2 (0.2) CH3CN (0.2) CH3CN (0.5) CH3CN (0.1) CH3CN (0.5) CH3CN (0.5) CH3CN (0.5) CH3CN (0.5) CH3CN (0.5) CH3CN (0.5) CH3CN (0.5)
was increased from 0.1 to 0.5 M (Table 1, entries 8−10). Using water as an additive further increased the yield to 77%. To create a greener reaction, the catalyst loading and amount of DMAD were decreased. As a result, the yield slightly increased to 78% with 1 mol % of catalyst loading and 2 equiv of DMAD (Table 1, entry 16). Control experiments revealed that both light and Fukuzumi acridinium salt were necessary for the cycloaddition to occur (Table 1, entries 17 and 18). After detailed screening of the reaction conditions, we found the best result was obtained with 2 equiv of DMAD and 1 mol % of Fukuzumi acridinium salt (Acr+Mes) in acetonitrile (0.5 M) at room temperature to afford our desired product 3a in 78% yield. After optimization of the reaction conditions, we next examined the [3 + 2] cycloaddition of oxaziridine 1a with different electron deficient alkynes 2 (Scheme 2). A variety of alkynes (2b−e) was tolerated and gave the corresponding 4isoxazolines (3b−e) in moderate to good yields. For alkynes with larger substituents such as diethyl acetylenedicarboxylate 2b and di-tert-butyl acetylenedicarboxylate 2c, the cycloaddition was inhibited by steric hindrance of the bulky ester groups. In particular, the cycloaddition of oxaziridine 1a with di-tert-butyl acetylenedicarboxylate 2c gave the corresponding adduct 3c in only 29% yield. Because of the low solubility of dibenzoylacetylene 2d in MeCN, the corresponding 4-isoxazoline 3d was formed in a moderate 43% yield. The monoactivated methyl phenylpropiolate 2e gave the corresponding adduct 3e in 35% yield under modified reaction conditions. Next, we turned our attention to the [3 + 2] cycloaddition of a broad range of substituted oxaziridines 1 with DMAD 2a (Scheme 3). Under the optimized reaction conditions, various oxaziridines 1 containing electron-neutral, electron-rich, or electron-deficient functional groups such as alkyl, alkoxy, and halogen were reacted with acetylenedicarboxylate 2a to afford the corresponding 4-isoxazolines (3f−ah) in good to excellent yields. Para-substituted alkylaryl oxaziridines (1f−l) gave the desired products (3f−l) in 85−88% yield. Slightly lower yields were observed for electron-deficient halogen-substituted aryl oxaziridines (1j−l). Notably, para- and meta-substituted methyl- or chloroaryl oxaziridines (1f,l,m,n) did not influence steric hindrance in the [3 + 2] cycloaddition. However, orthosubstituted methyl- or chloroaryl oxaziridines (1o,p) gave the corresponding 4-isoxazolines 3o and 3p in 37% and 19% yield,
nd nd 55 52 13 71 72 74 65 77 76 75 76 78 nd nd
a
Reaction conditions: 1a (0.2 mmol), 2a (quantity noted), catalyst (quantity noted), additive (250 mol %), solvent (quantity noted) with 6 W blue LEDs irradiation at room temperature for 24 h under argon in pressure tubes. bIsolated yield by flash column chromatography. cIn the absence of light source. nd = not detected.
and the structure was confirmed by single-crystal X-ray analysis (Scheme 2 and Supporting Information). Other catalysts did not work in the designed reaction with the exception of Ru(bpy)3Cl2, which gave the product in a trace amount (Table 1, entries 1−4). To generate the active radical cation species, oxidation of the oxaziridine is essential. However, oxaziridines have a higher oxidation potential than other amines because of the oxaziridine oxygen. We speculate that the high oxidization ability of Fukuzumi acridinium salt in the excited state (+ 2.06 V) is sufficient to oxidize the oxaziridine.12 The influence of solvent on the cyclization efficiency was also significant; when acetonitrile and nitromethane were chosen as the solvent, the yield was enhanced to 72% and 71%, respectively (Table 1, entries 6−9). We chose acetonitrile as the reaction solvent because it is a more commonly used solvent than nitromethane. The yield was slightly increased to 74% when the concentration of the solution 6449
DOI: 10.1021/acs.orglett.7b03369 Org. Lett. 2017, 19, 6448−6451
Letter
Organic Letters Scheme 3. Substrate Scope of Various Oxaziridinesa
Scheme 4. (a) Gram-Scale Reaction. (b) Hydrogenation of 4Isoxazolines. (c) Thermal Rearrangement of 4-Isoxazolines
1a, which indicates involvement of an SET mechanism (detailed in the SI). Next, radical-trapping experiments were undertaken. The addition of TEMPO or γ-terpinene to the cycloaddition completely suppressed the reaction, indicating that the reaction involves a radical process (detailed in the SI). On the basis of the reported literature11,12 and the above control experiments, a plausible mechanism for the photoinduced [3 + 2] cycloaddition is depicted in Scheme 5. Initially,
a
Reaction conditions as given in Table 1, entry 16; reported yields are for isolated material. b48 h. cEtOAc (0.5 M) was used as solvent, without H2O, 48 h. See the Supporting Information for details.
respectively, which shows that nitrone production and the subsequent cycloaddition with ortho-substituted aryl oxaziridines were influenced by steric hindrance. Remarkably, 3,4-disubstituted aryl oxaziridine 1q and 4,4′-disubstituted aryl oxaziridines (1r−ab) worked well, providing the corresponding products 3r−ab in 41−90% yield. In the case of electrondonating methoxy-substituted aryl oxaziridines (1i,w,z), the methoxy group accelerated oxaziridine oxidation as well as decomposition of oxaziridines to ketones. Therefore, we observed ketones as byproducts while generating the corresponding 4-isoxazolines 3i,w,z in 41−62% yield. In addition, the 3,3-diaryl oxaziridines can be successfully extended to 3-alkyl-3aryl, 3-aryl, and 3-vinyl oxaziridines (2ac−ah) for visible-lightmediated cycloaddition. These oxaziridines gave the corresponding 4-isoxazolines (3ac−ah) in 48−65% yields. To demonstrate the efficiency of this method, we conducted the gram-scale synthesis of 4-isoxazoline 3a. The [3 + 2] cycloaddition of oxaziridine 1a (1 g, 3.36 mmol) with DMAD 2a (0.84 mL, 6.72 mmol) afforded the 4-isoxazoline 3a in 70% yield using modified reaction conditions for the larger scale (Scheme 4, a). 4-Isoxazolines (3a,t) were easily converted in good yield to the tetrasubstituted allylic alcohols (4a,t) by N−O bond cleavage followed by deamination and reduction of ketone in the present of zinc powder and NH4Cl as hydrogen source (Scheme 4, b).13 In addition, thermal rearrangement of the 4-isoxazolines (3a,t) led directly to enamines (5a,t) (Scheme 4, c).14 To gain a better understanding of the reaction mechanism, additional experiments were carried out. First, electrochemical analysis and Stern−Volmer luminescence quenching studies were performed. The oxidation potential of oxaziridine 1a was measured by cyclic voltammetry to be +2.06 V vs SCE, indicating that the oxaziridine can be oxidized by Fukuzumi acridinium salt in the excited state (+2.06 V vs SCE).15 In Stern−Volmer luminescence quenching experiments, the excited state of the photoredox catalyst (Acr+-Mes*) was quenched by oxaziridine
Scheme 5. Proposed Reaction Mechanism
the acridinium catalyst (Acr+-Mes) is excited (Acr+-Mes*) under visible-light irradiation. Single-electron oxidation of oxaziridine 1a by the photocatalyst excited state (Acr+-Mes*) generates radical cation I along with reduced photocatalyst (Acr•-Mes). Radical cation I is then converted to the nitrone radical II in a ring-opening process. Single-electron reduction of nitrone radical II with Acr•-Mes regenerates the photoredox catalyst (Acr+-Mes) and forms nitrone III, which can be isolated by column chromatography under standard reaction conditions. Subsequent [3 + 2] cycloaddition of nitrone III with DMAD 2a provides 4-isoxazoline 3a. Next, the quantum yield of the photoinduced [3 + 2] cycloaddition of 1a with 2a was determined to be Φ = 0.149 ± 0.039.16 We conducted on−off experiments and reactionmonitoring experiments by 1H NMR and HPLC. These results showed that continuous irradiation of visible light is essential for the cycloaddition, a radical chain propagation mechanism is not 6450
DOI: 10.1021/acs.orglett.7b03369 Org. Lett. 2017, 19, 6448−6451
Letter
Organic Letters
(3) (a) Hussain, S. A.; Sharma, A. H.; Perkins, M. J.; Griller, D. J. Chem. Soc., Chem. Commun. 1979, 289. (b) Soldaini, G.; Cardona, F.; Goti, A. Org. Lett. 2007, 9, 473. (c) Gella, C.; Ferrer, È.; Alibés, R.; Busqué, F.; de March, P.; Figueredo, M.; Font, J. J. Org. Chem. 2009, 74, 6365. (4) Stappers, F.; Broeckx, R.; Leurs, S.; Van Den Bergh, L.; Agten, J.; Lambrechts, A.; Van den Heuvel, D.; De Smaele, D. Org. Process Res. Dev. 2002, 6, 911. (5) (a) Guinchard, X.; Vallée, Y.; Denis, J.-N. Org. Lett. 2005, 7, 5147. (b) Guinchard, X.; Denis, J.-N. J. Org. Chem. 2008, 73, 2028. (c) Gioia, C.; Fini, F.; Mazzanti, A.; Bernardi, L.; Ricci, A. J. Am. Chem. Soc. 2009, 131, 9614. (d) Gini, A.; Segler, M.; Kellner, D.; Mancheño, O. G. Chem. Eur. J. 2015, 21, 12053. (6) (a) Yoon, T. P.; Ischay, M. A.; Du, J. N. Nat. Chem. 2010, 2, 527. (b) Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102. (c) Xuan, J.; Xiao, W.-J. Angew. Chem., Int. Ed. 2012, 51, 6828. (d) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322. (e) Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016, 116, 10075. (f) Shaw, M. H.; Twilton, J.; MacMillan, D. W. C. J. Org. Chem. 2016, 81, 6898. (g) Zhou, L.; Lokman Hossain, M.; Xiao, T. Chem. Rec. 2016, 16, 319. (7) (a) Rueping, M.; Leonori, D.; Poisson, T. Chem. Commun. 2011, 47, 9615. (b) Zou, Y.-Q.; Lu, L.-Q.; Fu, L.; Chang, N.-J.; Rong, J.; Chen, J.-R.; Xiao, W.-J. Angew. Chem., Int. Ed. 2011, 50, 7171. (c) Maity, S.; Zhu, M.; Shinabery, R. S.; Zheng, N. Angew. Chem., Int. Ed. 2012, 51, 222. (d) Hou, H.; Zhu, S.; Pan, F.; Rueping, M. Org. Lett. 2014, 16, 2872. (e) Xuan, J.; Xia, X.-D.; Zeng, T.-T.; Feng, Z.-J.; Chen, J.-R.; Lu, L.-Q.; Xiao, W.-J. Angew. Chem., Int. Ed. 2014, 53, 5653. (f) Zeng, T.-T.; Xuan, J.; Ding, W.; Wang, K.; Lu, L.-Q.; Xiao, W.-J. Org. Lett. 2015, 17, 4070. (g) Chen, L.; Li, H.; Li, P.; Wang, L. Org. Lett. 2016, 18, 3646. (h) Alfonzo, E.; Alfonso, F. S.; Beeler, A. B. Org. Lett. 2017, 19, 2989. (8) (a) Freeman, J. P. Chem. Rev. 1983, 83, 241. (b) Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2010, 2010, 3363. (c) Chukanov, N. V.; Reznikov, V. A. Russ. Chem. Bull. 2011, 60, 379. (9) (a) Padwa, A.; Kline, D. N.; Koehler, K. F.; Matzinger, M.; Venkatramanan, M. K. J. Org. Chem. 1987, 52, 3909. (b) Lopes, S. M. M.; Nunes, C. M.; Pinho e Melo, T. M. V. D. Tetrahedron 2010, 66, 6078. (c) Xiao, Z.-F.; Ding, T.-H.; Mao, S.-W.; Ning, X.-S.; Kang, Y.-B. Adv. Synth. Catal. 2016, 358, 1859. (10) (a) Stoner, E. J.; Roden, B. A.; Chemburkar, S. Tetrahedron Lett. 1997, 38, 4981. (b) Aschwanden, P.; Frantz, D. E.; Carreira, E. M. Org. Lett. 2000, 2, 2331. (c) Debleds, O.; Zotto, C. D.; Vrancken, E.; Campagne, J.-M.; Retailleau, P. Adv. Synth. Catal. 2009, 351, 1991. (d) Wada, N.; Kaneko, K.; Ukaji, Y.; Inomata, K. Chem. Lett. 2011, 40, 440. (e) Chandrasekhar, B.; Ahn, S.; Ryu, J.-S. J. Org. Chem. 2016, 81, 6740. (11) (a) Iwano, Y.; Kawamura, Y.; Miyoshi, H.; Yoshinari, T.; Horie, T. Bull. Chem. Soc. Jpn. 1994, 67, 2348. (b) Iwano, Y.; Kawamura, Y.; Horie, T. Chem. Lett. 1995, 24, 67. (c) Ohba, Y.; Kubo, K.; Sakurai, T. J. Photochem. Photobiol., A 1998, 113, 45. (12) (a) Fukuzumi, S.; Kotani, H.; Ohkubo, K.; Ogo, S.; Tkachenko, N. V.; Lemmetyinen, H. J. Am. Chem. Soc. 2004, 126, 1600. (b) Ohkubo, K.; Mizushima, K.; Iwata, R.; Souma, K.; Suzuki, N.; Fukuzumi, S. Chem. Commun. 2010, 46, 601. (13) (a) Khan, F. A.; Dash, J.; Sudheer, C.; Gupta, R. K. Tetrahedron Lett. 2003, 44, 7783. (b) Aschwanden, P.; Geisser, R. W.; Kleinbeck, F.; Carreira, E. M. Org. Lett. 2005, 7, 5741. (c) Kelly, S. M.; Lipshutz, B. H. Org. Lett. 2014, 16, 98. (14) (a) Chukanov, N. V.; Popov, S. A.; Romanenko, G. V.; Reznikov, V. A. Tetrahedron 2008, 64, 7432. (b) Chukanov, N. V.; Popov, S. A.; Drebushchak, T. N.; Reznikov, V. A. Russ. Chem. Bull. 2010, 59, 1817. (15) (a) Rehm, D.; Weller, A. Isr. J. Chem. 1970, 8, 259. (b) Tucker, J. W.; Stephenson, C. R. J. J. Org. Chem. 2012, 77, 1617. (16) (a) Meyer, A. U.; Slanina, T.; Yao, C.-J.; König, B. ACS Catal. 2016, 6, 369. (b) Megerle, U.; Lechner, R.; Konig, B.; Riedle, E. Photochemical & Photobiological Sciences 2010, 9, 1400.
the predominant pathway, and that the reaction rate of nitrone formation by SET is faster than [3 + 2] cycloaddition (detailed in the SI). In conclusion, we developed a greener method for preparation of 4-isoxazolines in a visible-light photoredox-catalyzed [3 + 2] cycloaddition of oxaziridines with alkynes. This method involves in situ generation of nitrones from oxaziridines by SET. The [3 + 2] cycloaddition tolerates various functional groups and provides good to excellent yields. The cyclization products can be conveniently converted into tetrasubstituted allylic alcohols and enamines. Moreover, a plausible reaction mechanism was proposed based on electrochemical analysis, control experiments, and reaction monitoring. Development of an asymmetric synthesis of 4-isoxazolines is currently underway.
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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.7b03369. Electrochemical and photophysical measurements and mechanism studies; experimental procedures; spectroscopic data for all new compounds (1H NMR, 13C NMR, 19 F NMR, IR, HRMS), including images of NMR spectra and crystallographic data for 3a (PDF) Accession Codes
CCDC 1563016 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 data_
[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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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Sang Kook Woo: 0000-0002-8808-037X Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was supported by the National Research Foundation (NRF-2016R1D1A1B03934062) and the Priority Research Centers Program (NRF-2009-0093818) funded by the Ministry of Education of the Republic of Korea, and this work has been performed with the financial assistance of the Ulsan Green Environment Center (UGEC), Korea.
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REFERENCES
(1) For selected reviews, see: (a) Gothelf, K. V.; Jørgensen, K. A. Chem. Rev. 1998, 98, 863. (b) Jones, R. C. F., Nitrones. In Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products; John Wiley & Sons, Inc.: New York, 2003; p 1. (c) Pellissier, H. Tetrahedron 2007, 63, 3235. (d) Stanley, L. M.; Sibi, M. P. Chem. Rev. 2008, 108, 2887. (e) Hashimoto, T.; Maruoka, K. Chem. Rev. 2015, 115, 5366. (2) (a) Grigor’ev, I. A., Nitrones: Novel Strategies in Synthesis. In Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis; John Wiley & Sons, Inc.: Hoboken, NJ,2007; p 129. (b) Pfeiffer, J. Y.; Beauchemin, A. M. J. Org. Chem. 2009, 74, 8381. 6451
DOI: 10.1021/acs.orglett.7b03369 Org. Lett. 2017, 19, 6448−6451
