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Cite This: J. Org. Chem. 2018, 83, 1867−1875

Photochemically Induced Intramolecular Radical Cyclization Reactions with Imines Corentin Lefebvre,† Clément Michelin,† Thomas Martzel,† Vaneck Djou’ou Mvondo,† Véronique Bulach,‡ Manabu Abe,*,§,∥ and Norbert Hoffmann*,† †

CNRS, Université de Reims Champagne-Ardenne, ICMR, Equipe de Photochimie, UFR Sciences, B.P. 1039, 51687 Reims, France Laboratoire de Tectonique Moléculaire (UMR 7140), Institut Le Bel, Université de Strasbourg, 4, rue Blaise Pascal, 67000 Strasbourg, France § Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan ∥ Hiroshima Research Center for Photo-Drug-Delivery Systems (Hi-P-DDS), 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan ‡

S Supporting Information *

ABSTRACT: The photochemically induced intramolecular hydrogen abstraction or hydrogen atom transfer in cyclic imines 8a,b followed by a cyclization is investigated. Two types of products are observed, one resulting from the formation of a C−C bond, the other from the formation of a C−N bond. A computational study reveals that hydrogen is exclusively transferred to the imine nitrogen leading to a triplet diradical intermediate. After intersystem crossing, the resulting zwitterionic intermediate undergoes cyclization leading to the final product.

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under similar photochemical conditions.10 Other chromophores such as imides also undergo similar transformations.11,12 Recently, similar reactions of α,β-unsaturated lactones of furanones such as 1 have been studied (Scheme 1).13−15 These reactions can be carried out in the presence of acetone as a triplet sensitizer. After the triplet energy transfer onto the furanone 1, the ππ* triplet 2 possessing a high spin density in the β position16 is generated. Due to the increased reactivity in this position, the hydrogen atom is transferred to the β position of the furanone moiety, and the diradical intermediate 3 is generated. After the radical combination, the final spirocyclic products 4a,b are formed. Depending on the structure variations, a hydrogen atom can also be transferred from other positions of the donor moiety. In our previous investigation,13 the stereo- and regioselectivity have been studied in detail. Mechanistic details of the hydrogen-transfer

INTRODUCTION

Currently, photochemical reactions are intensively investigated for application to organic synthesis.1−4 Because of the change of electronic configuration at the electronically excited state in comparison with that of the ground state, the chemical reactivity including the chemoselectivity and regioselectivity is considerably modified.5 Mechanistic investigations of such transformations facilitates optimization and efficient application to synthesis. The Norrish−Yang (NY) cyclization6,7 is one of these reactions which were often applied in this context. In the context of sustainable chemistry, the photoinduced chemical transformation is also very important since C−C bonds are formed without any chemical activation (the photon as traceless reagent).8 Furthermore, C−H activation9 is possible in the absence of additional chemical reagents. In these reactions, a carbonyl functional group is electronically excited. A hydrogen transfer then occurs which leads to the formation of a diradical intermediate. The radical combination yields the final cyclization products. Macrocyclizations are also possible © 2018 American Chemical Society

Received: November 6, 2017 Published: January 15, 2018 1867

DOI: 10.1021/acs.joc.7b02810 J. Org. Chem. 2018, 83, 1867−1875

Article

The Journal of Organic Chemistry Scheme 1. Intramolecular Hydrogen Abstractiona at the ππ* Triplet State of Furanones

a

Hydrogen atom transfer, HAT.

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step17,18 and the consequences for the outcome of such reactions has been discussed.13,19 Most frequently, hydrogen transfer from the donor moiety to the photochemical excited chromophore may occur according to a one-step mechanism in which the proton and the electron are transferred in the same time or, in a two-step process, the electron is transferred first and the proton follows. These mechanistic steps of hydrogen atom transfer (HAT) can also be discussed in connection with proton-coupled electron transfer (PCET) which is, for example, currently performed for photoredox catalytic reactions.20 We decided to replace the CH group in the β position of a furanone moiety (structure A) by a nitrogen atom, and we became interested in the photochemical reactivity of cyclic imines (structure B) (Figure 1). In contrast to the corresponding carbonyl compounds,

RESULTS AND DISCUSSION Cyclic imines possessing the core structure B as depicted in Figure 1 were synthesized starting with the oxazolone derivative 5 (Scheme 2).26,27 The alkylation of such compounds is reported to occur efficiently at the 4 position carrying the trifluoromethyl group.26,28,29 The Michael reactions with acrolein and crotonaldehyde yielded the adducts 6 and 7 respectively. Acetalization with ethylene glycol or 1,3dhydroxypropanol gave the corresponding acetales 8a, 9a, 8b, and 9b, respectively. When compound 8b was irradiated at λ = 300 nm in acetonitrile, two products 10b and 11b were isolated (Scheme 3). Compound 10b was formed in the photochemical reaction. When the reaction mixture was heated to 65 °C, compound 10b was completely converted into 11b. In this case, 11b was isolated with a yield of 83% as a single product. At room temperature, the thermal transformation was slow in acetonitrile. Thus, a crystalline sample of compound 10b was obtained, and the structure was determined by X-ray diffraction analysis (see the Supporting Information). Using the Norrish type II reaction of valerophenone as an actinometer,30 a high quantum yield of φ = 0.7 was determined for the conversion of 8b. When compound 8a was irradiated under the same conditions, compound 11a was formed and no corresponding primary cyclization product 10a was detected. Obviously, the thermal decarboxylation is more efficient than in the case of 10b. To our surprise, compound 12a was detected resulting from the formation of the C−N bond. The structure was determined by X-ray diffraction analysis (see the Supporting Information). We have also performed the reaction of compound 8a in (trifluoromethyl)benzene as an apolar solvent. Interestingly, the portion of 12a is considerably reduced (1.4%,

Figure 1. Furanones and related imine compounds.

photochemical reactions with electronically excited imines have been much less studied.21,22 Recently, systematic investigations have been carried out on intramolecular hydrogen abstraction of aromatic electronically excited imines.23 In such cases, aminoazaxylene intermediates are generated.24 Imines are valuable intermediates in organic synthesis.25 Photochemical reactions further enlarge the fields of application to organic synthesis.

Scheme 2. Synthesis of Cyclic Imines for Photochemical Transformations

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The Journal of Organic Chemistry Scheme 3. Photochemical Transformation of Cyclic Imines 8a and 8b

Scheme 4. Mechanistic Discussion for the Photochemical Transformation of Imines 8a and 8b

that these compound could not be isolated. Such a mechanism was previously suggested for the similar reactions with α,βunsaturated butyrolactones.13,14 The regioselectivity of the cyclization observed in this reaction also resembles that observed for similar reactions with carbonyl compounds.6,7,10 The compound 12a might be generated via hydrogen abstraction at the carbon atom of the imine function, leading to intermediate 14. We argued, however, that the formation of such nitrogen-centered radicals is unfavorable. A computational study was performed to obtain quantitative data on such hydrogen-transfer steps. First, the triplet states of compounds 8a and 8b were computed at the UB3LYP/6-31G(d)32 level of theory with the Gaussian 09 suite of programs,33 respectively. The spin

of isolated yield) under these conditions. Furthermore, the yield of 11a increased. The transformation is also faster. We assume that compounds 8a,b after photochemical excitation undergo intersystem crossing and the first chemical reaction step will occur at the triplet state. Intramolecular hydrogen transfer from the acetal moiety to the imine nitrogen atom leads to intermediate 13 (Scheme 4). It must be pointed out that this hydrogen transfer occurs in one step in which the electron and the proton are transferred simultaneously.19 A corresponding two-step process in which an electron is first transferred and the proton then follow may be excluded. Singleelectron transfer from acetal functions is very difficult.31 Radical combination in intermediate 13 leads to cyclization products such as 10a,b. In the case of 10a, fast decarboxylation occurs so 1869


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The Journal of Organic Chemistry

acetal moiety by the nitrogen atom (path a (NH)) was calculated to be the most energetically favored pathway to give the corresponding triplet diradical T-DRNH. Other hydrogen abstraction pathways, path b (CH) and path c (OH), were found to be energetically less favored than path a by ∼15 and ∼25 kcal mol−1, respectively, indicating that path a should be the exclusive reaction from 38a and 38b to afford T-DRa,bNH. The higher spin density at the nitrogen atom in 38 than the αcarbonyl methyl radical moiety is responsible for the lower energy barrier. The triplet diradical intersystem crosses to produce the singlet state S-DRaNH, which should have a zwitterionic character as depicted in the resonance structure.34 The CC coupling reaction, i.e., C-attack, produces the bicyclo[3.2.1]octane derivative 10. The bicyclo[3.3.0]octane derivative 12 is formed in the NC coupling reaction, i.e., N-attack, from the singlet state of the diradical species. A computational study on the C−C and N−C bond formation in acetonitrile at the M062x level of theory has been performed. We could not find any transition-state structures, which means that the both of the bond formation steps are barrierless processes. Due to the zwitterionic character of S-DRNH, the regioselectivity (de-

distribution in the triplet states is summarized in Figure 2. In both triplet states 38a and 38b, one of the two spins is mainly

Figure 2. Spin-density distribution of the triplet states 38b and 38a.

localized at the nitrogen atom, 0.78. Another spin is highly delocalized to the phenyl ring. As expected, the spin-density distribution was not affected by the acetal moiety. The hydrogen abstraction reactions in 38b and 38a were computed at the same level of theory (Scheme 5). As clearly shown in Scheme 5, the hydrogen abstraction reaction at the

Scheme 5. Calculations (UB3LYP/6-31G(d)) of Different Hydrogen-Transfer Steps at the Triplet Excited State of 8a,ba

a

Energies are reported in kcal mol−1. 1870


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competition between the formation of a C−C and the C−N bond. The regioselectivity in the cyclization step is further affected by the presence or absence of a methyl substituent at the side chain tether.

scribed in Scheme 3 for the transformation of 8a) is affected by the solvent polarity during the final cyclization. A very similar mechanism has recently been proposed for a photochemically induced intramolecular hydrogen abstraction in naphthoquinone derivatives.35 As in our case, diradical intermediates are formed. An intramolecular electron transfer has been discussed yielding zwitterionic intermediates, which leads to the formation of a C−O bond via charge combination. As we have previously shown for similar reactions with α,βunsaturated butyrolactones, attaching a substituent on the linker may have influence on the regioselectivity of the cyclization step.13 Conformational equilibria are affected by this substituent and thus have an influence on the regioselectivity of hydrogen abstraction. We have transformed compounds 9a,b carrying a methyl group at the linker under the same conditions (Scheme 6). In the case of the dioxolane

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General Information. NMR spectra were recorded with a Bruker AC 250 (250 MHz for 1H and 62 MHz for 13C) or a Bruker DRX 500 (500 MHz for 1H and 125 MHz for 13C). Chemical shifts are given in ppm relatively to TMS using residual solvent signals as secondary references. IR spectra were recorded on a Nicolet AVATAR 320 FTIR. UV spectra were recorded with a UVKON 941 PLUS (KONTRON Instruments). GCMS and MS analysis were performed with Termoquest CE Instruments (Trace GC: 2000 series, Finnigan Trace MS). UV irradiation has been performed with Rayonet reactors (The Southern New England Ultraviolet Company, Branford, CT) at λ = 350 nm. The reaction mixture was irradiated in Pyrex tubes (Ø = 0.9 cm). Preparative chromatography was carried out with silica gel 60A from Carlo Erba Reactifs-SDS. TLC was carried out with Kieselgel 60F254 plates form Merck. X-ray diffraction: data were collected at 173(2) K on a Bruker APEX8 CCD diffractometer equipped with an Oxford Cryosystem liquid N2 device, using a molybdenum microfocus sealed tube generator with mirror-monochromated Mo−Kα radiation (λ = 0.71073 Å), operated at 50 kV/600 mA. The diffraction data were corrected for absorption. Structures were solved using SHELXS-97 and refined by full matrix least-squares on F2 using SHELXL-97. The hydrogen atoms were introduced at calculated positions and not refined (riding model).36 They can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/ datarequest/cif (CCDC nos. 1583694 (16a), 1583695 (10b), 1583696 (12a)). Synthesis of 4-Phenyl-2-(trifluoromethyl)oxazol-5(2H)-one (5).37 2-Amino-2-phenylacetic acid (22.0 g, 146 mmol, 1.0 equiv) was dissolved in 2,2,2-trifluoroacetic anhydride (122.4 g, 81 mL, 583 mmol, 4.0 equiv) at 0 °C. The reaction mixture was stirred at 70 °C during 3 h and cooled to room temperature, and then the remaining 2,2,2-trifluoroacetic anhydride was removed under reduced pressure. The crude product was dissolved in DCM and washed with satd NaHCO3 until pH was neutral. A last washing with satd NaCl was performed, and the organic layers were dried over MgSO4, filtered, and removed under reduced pressure to give a white/yellow crystalline solid. Recrystallization in n-hexane gave compound 5 as a white crystalline solid in 92% yield (30.7 g, 134 mmol). Rf = 0.51 (n-hexane: Ethyl acetate, 90:10). Melting range = 89−90 °C. UV/vis (acetonitrile): ε = 13500 (λmax = 271 nm), 4400 (λ = 300 nm) L· cm−1·mol−1. 1H NMR (500 MHz, CDCl3, ppm): δ = 6.26 (q, J = 6.26 Hz, 1 H), 7.54 (m, 2 H), 7.65 (tt, J = 1.5, 8 Hz, 1 H), 8.44 (dd, J = 1.5, 8.5 Hz, 2 H). 13C (125 MHz, CDCl3, ppm): δ = 92.5 (q, J = 35.5 Hz), 120.5 (q, J = 282 Hz), 127.4, 129.2, 129.3, 134.1, 160.8, 162.9. 19F (250 MHz, CDCl3, ppm): δ = −79.04 (d, J = 4 Hz). IR (ν): 1800, 1614, 1341, 1304, 1202, 1156, 968, 867 cm−1. LRMS (ESI-TOF) m/z: [M + H]+ calcd for C10H7F3NO2 230, found 230. Synthesis of 3-(5-Oxo-4-phenyl-2-(trifluoromethyl)-2,5-dihydrooxazol-2-yl)propanal (6). 4-Phenyl-2-(trifluoromethyl)oxazol-5(2H)-one 5 (10.0 g, 43.6 mmol, 1.0 equiv) and triethylamine (4.42 g, 6.08 mL, 43.6 mmol, 1.0 equiv) were added in 400 mL of DCM. Acrylaldehyde (2.45 g, 2.92 mL, 43.6 mmol, 1.0 equiv) was then added dropwise. The reaction mixture was vigorously stirred during 30 min. DCM was removed under reduced pressure, and the crude product was purified via flash chromatography (petroleum ether/ethyl acetate, 90:10) to give 3-(5-oxo-4-phenyl-2-(trifluoromethyl)-2,5-dihydrooxazol-2-yl)propanal (6) as a yellow viscous oil in 90% yield (11.20 g, 393 mmol). Rf = 0.47 (petroleum ether/ethyl acetate, 80:20). 1H NMR (600 MHz, CDCl3 ppm): δ = 2.44 (ddd, J = 5.5, 9.5, 18.5 Hz, 1 H), 2.53 (ddd, J = 5.5, 9.5, 18.5 Hz, 1 H), 2.64 (ddd, J = 5.5, 9.5, 15 Hz, 1 H), 2.69 (ddd, J = 5.5, 9.5, 15 Hz, 1 H), 7.53 (m, 2 H), 7.66 (tt, J = 1.5, 7.5 Hz, 1 H), 8.41 (dd, J = 1.5, 8.5 Hz, 2 H), 9.73 (t, J = 1 Hz, 1 H). 13C NMR (150 MHz, CDCl3, ppm): δ =

Scheme 6. Photochemical Transformation of Cyclic Imines 8a and 8ba

a

EXPERIMENTAL SECTION

The influence of a methyl substituent on the regioselectivity is shown.

derivative 9a, the effect of the methyl substituent is small. The yield of the product resulting from the cyclization in the α position at the imine carbon is slightly improved. In the case of the dioxane derivative 9b, the formation of compound 16b resulting from cyclization at the nitrogen atom of the imine function is enabled, while the yield of the corresponding compound 15b resulting from cyclization at the carbon atom of the imine function is reduced (compare Scheme 3). In contrast to the previously reported reactions of furanone derivatives,13 hydrogen abstraction always occurs at the same site (imine nitrogen) in the present case. Conformational equilibria affected by the methyl substituent should therefore influence the regioselectivity in the final cyclization step and not in the hydrogen-abstraction step.

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CONCLUSION Under photochemical reaction conditions, cyclic imines (oxazolones) undergo intramolecular hydrogen abstraction followed by cyclization. In contrast to similar reactions with carbonyl or α,β-unsaturated lactones, two different regioisomers are obtained. The formation of a C−N bond in of these isomers is unusual. A computational study suggests that after intersystem crossing of the triplet hydrogen is transferred exclusively to the imine nitrogen atom the resulting diradical intermediate undergoes intersystem crossing and the resulting singlet state possesses a zwitterionic character. The final step is therefore strongly characterized by the charge combination. It determines the regioselectivity of the reaction and, thus, the 1871


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The Journal of Organic Chemistry 24.3, 36.0, 100.5 (q, J = 31 Hz), 121.7 (q, J = 285 Hz), 127.2, 129.2, 129.4, 134.2, 160.7, 162.6, 198.5. 19F NMR (250 MHz, CDCl3, ppm): δ = −80.18. IR (ν): 2837, 2734, 1575, 1386, 1302, 1269 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C13H11F3NO3 286.0691, found 286.0699. Synthesis of 3-(5-Oxo-4-phenyl-2-(trifluoromethyl)-2,5-dihydrooxazol-2-yl)butanal (7). 4-Phenyl-2-(trifluoromethyl)oxazol5(2H)-one (5) (10.0 g, 43.6 mmol, 1.0 equiv) and triethylamine (4.42 g, 6.08 mL, 43.6 mmol, 1.0 equiv) were added in 400 mL of DCM. Crotonaldehyde (3.06 g, 3.62 mL, 43.6 mmol, 1.0 equiv) was then added dropwise. The reaction mixture was vigorously stirred during 30 min. DCM was removed under reduced pressure, and the crude product was purified via flash chromatography (petroleum ether/ethyl acetate, 90:10) to give 3-(5-oxo-4-phenyl-2-(trifluoromethyl)-2,5dihydrooxazol-2-yl)propanal (7) as a yellow liquid in 87% yield (11.36 g, 393 mmol). Rf = 0.42 (petroleum ether/ethyl acetate, 90:10). 1 H NMR (600 MHz, CDCl3, ppm): δ = 1.17 (d, J = 7 Hz, 3 H), 2.44 (dd, J = 9, 18 Hz, 1 H; dia 1), 2.51 (dd, J = 9, 18 Hz, 1 H; dia 2), 2.77 (dd, J = 4, 18 Hz, 1 H; dia 2), 2.83 (dd, J = 3.5, 18 Hz, 1 H; dia 1), 3.14 (m, 1 H; dia 1), 3.18 (m, 1H; dia 2), 7.53 (t, J = 7.5 Hz, 2H), 7.65 (tt, J = 1.5,7.5 Hz, 1H), 8.41 (m, 2H), 9.74 (s,1H; dia 2), 9.75 (s, 1 H; dia 1). 13C NMR (150 MHz, CDCl3, ppm): δ = 14.4 (dia 2), 14.8 (dia 1), 32.0 (dia 2), 44.8 (dia 2), 45.0 (dia 1), 102.15 (d, J = 30 Hz, dia 2), 102.23 (q, J = 30 Hz, dia 1), 122 (q, J = 286.5 Hz), 127.25 (dia 2), 127.32 (dia 1), 129.2, 129.3 (dia 1), 129.4 (dia 2), 134.1 (dia 1), 134.2 (dia 2), 160.3 (dia 1), 160.5 (dia 2), 162.7, 198.8 (dia 1), 198.9 (dia 2). 19F NMR (250 MHz, CDCl3, ppm): δ = −75.97, − 75.80. IR (ν): 2833, 2731, 1465, 1318 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C14H13NO3F3 300.0848, found 300.0857. Synthesis of 2-(2-(1,3-Dioxolan-2-yl)ethyl)-4-phenyl-2(trifluoromethyl)oxazol-5(2H)-one (8a). In a 100 mL flask equipped with an inverse Dean−Stark trap was dissolved 3-(5-oxo-4phenyl-2-(trifluoromethyl)-2,5-dihydrooxazol-2-yl)propanal (6) (1.3 g, 4.6 mmol, 1.0 equiv) in 30 mL of CHCl3. Ethylene glycol was then added dropwise (2.11 g, 1.9 mL, 34 mmol, 7.0 equiv) with PTSA (0.05 g, 0.285 mmol, 0.1 equiv). The reaction mixture was vigorously stirred and refluxed during 1 h 30. Without cooling, the reaction mixture was treated with 30 mL of NaHCO3. The organic layer was then dried over MgSO4, filtered, and removed under reduced pressure to give a yellow and viscous oil. The crude product was purified via flash chromatography (petroleum ether/diethyl ether, 90:10) to give 2-(2(1,3-dioxolan-2-yl)ethyl)-4-phenyl-2-(trifluoromethyl)oxazol-5(2H)one (8a) as a yellow and viscous oil in 82% yield (1.24 g, 3.8 mmol). Rf = 0.25 (petroleum ether/diethyl ether, 90:10). 1H NMR (600 MHz, CDCl3, ppm): δ = 1.53−1.72 (m, 2 H), 2.45−2.56 (m, 2 H), 3.92− 4.04 (m, 2 H), 4.92 (t, J = 4.2 Hz, 1 H), 7.55 (t, J = 7.8 Hz, 2 H), 7.66 (t, J = 7.5 Hz, 1 H), 8.40−8.50 (m, 2 H). 13C NMR (150 MHz, CDCl3, ppm): δ = 25.4, 25.6, 65.07, 65.09, 101.0 (q, J = 31.0 Hz), 102.8, 121.7 (q, J = 285.2 Hz), 127.4, 128.99, 129.17, 133.8, 160.4, 162.8. 19F NMR (235 MHz, CDCl3, ppm): δ = −80.42. IR (ν): 1576, 1380, 1304, 1271, 1260 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H15NO4F3 330.0953, found 330.0960. Synthesis of 2-(1-(1,3-Dioxolan-2-yl)propan-2-yl)-4-phenyl2-(trifluoromethyl)oxazol-5(2H)-one (9a). In a 100 mL flask equipped with an inverse Dean−Stark trap was dissolved 3-(5-oxo-4phenyl-2-(trifluoromethyl)-2,5-dihydrooxazol-2-yl)butanal (7) (2.4 g, 8.02 mmol, 1.0 equiv) in 50 mL of CHCl3. Ethylene glycol was then added dropwise (2.45 g, 2.2 mL, 40.1 mmol, 5.0 equiv) with PTSA (0.14 g, 0.8 mmol, 0.1 equiv). The reaction mixture was vigorously stirred and refluxed during 1 h 30. Without cooling, the reaction mixture was treated with 50 mL of NaHCO3. The organic layer was then dried over MgSO4, filtered, and removed under reduced pressure to give a colorless and viscous oil. The crude product was purified via flash chromatography (petroleum ether/ethyl acetate, 95:5) to give 2(1-(1,3-dioxolan-2-yl)propan-2-yl)-4-phenyl-2-(trifluoromethyl)oxazol-5(2H)-one (9a) as a colorless and viscous oil in 80% yield (2.24 g, 6.42 mmol). Rf = 0.24 (petroleum ether/ethyl acetate, 95:5). 1H NMR (500 MHz, CDCl3, ppm): δ = 1.25 (d, J = 7 Hz, 3 H), 1.54 (ddd, J = 4, 10, 14 Hz, 1 H), 1.90 (dt, J = 3.5, 5.5, 14 Hz, 1 H), 2.74 (dqd, J = 305, 7, 10 Hz, 1 H), 3.83 (m, 2 H), 3.94 (m, 2 H), 4.94 (dd, J

= 4, 5.5 Hz, 1 H), 7.52 (t, J = 7.5, 8.5 Hz, 2 H), 7.62 (tt, J = 1.5, 7.5 Hz, 1 H), 8.41 (dd, J = 1.5, 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3, ppm): δ = 13.8 (dia 1), 14.4 (dia 2), 33.8 (dia 2), 34.3 (dia 2), 34.5 (dia 1), 64.77 (dia 1), 64.79 (dia 2), 65.1, 102.7 (dia 1), 102.8 (dia 2), 102.9 (q, J = 30 Hz), 122.1 (q, J = 287 Hz), 127.6 (dia 2), 129.08, 129.05, 133.8, 160.2 (dia 1), 160.4 (dia 2), 162.9 (dia 2), 163.0 (dia 1). 19F NMR (150 MHz, CDCl3, ppm): δ = −75.63,−75.61. IR (ν): 1801, 1617, 1390, 1292, 1200, 1169 cm−1. HRMS (ESI-TOF) m/ z: [M + H]+ calcd for C16H17NO4F3 344.1110, found 344.1111. Synthesis of 2-(2-(1,3-Dioxan-2-yl)ethyl)-4-phenyl-2(trifluoromethyl)oxazol-5(2H)-one (8b). In a 250 mL flask equipped with an inverse Dean−Stark trap was dissolved 3-(5-oxo-4phenyl-2-(trifluoromethyl)-2,5-dihydrooxazol-2-yl)propanal (6) (7.47 g, 26.2 mmol, 1.0 equiv) in 100 mL of CHCl3. Propane-1,3-diol was then added dropwise (16.01 g, 15.2 mL, 209.5 mmol, 8.0 equiv) with PTSA (0.5 g, 2.62 mmol, 0.1 equiv). The reaction mixture was vigorously stirred and refluxed during 1 h 30. Without cooling, the reaction mixture was treated with 30 mL of NaHCO3. The organic layer was then dried over MgSO4, filtered, and removed under reduced pressure to give a colorless oil. The crude product was purified via flash chromatography (petroleum ether/ethyl acetate, 90:10) to give (12) as a white powder in 83% yield. Melting range = 48−48.5 °C (7.50 g, 21.83 mmol). Rf = 0.43 (petroleum ether/ethyl acetate, 90:10). UV/vis (acetonitrile): ε = 12200 (λmax = 272 nm), 4400 (λ = 300 nm) L·cm−1· mol−1. 1H NMR (600 MHz, CDCl3, ppm): δ = 1.31 (m, 1 H), 1.48 (ddt, J = 5, 10.5, 14 Hz, 1 H), 1.55 (ddt, J = 5, 10.5, 14 Hz, 1 H), 2.02 (qt, J = 5, 13 Hz, 1 H), 2.47 (qdd, J = 5.5, 10, 14.5 Hz, 2 H), 3.72 (m, 2 H), 4.05 (ddd, J = 1.5, 5, 12 Hz, 2 H), 4.54 (t, J = 5 Hz, 1 H), 7.51 (t, J = 7.5 Hz, 2 H), 7.63 (t, J = 7.5 Hz, 1 H), 8.41 (d, J = 7.5 Hz). 13C NMR (150 MHz, CDCl3, ppm): δ = 25.7, 25.8, 27.1, 67.0, 100.6, 101.2 (q, J = 31 Hz), 121.9 (q, J = 285 Hz), 127.6, 129.1, 129.3, 133.9, 160.5, 163.00. 19F NMR (250 MHz, CDCl3, ppm): δ = −80.44. IR (ν): 1802, 1613, 1390, 1267, 1197 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H17NO4F3 344.1110, found 344.1109. Synthesis of 2-(1-(1,3-Dioxan-2-yl)propan-2-yl)-4-phenyl-2(trifluoromethyl)oxazol-5(2H)-one (9b). In a 250 mL flask equipped with an inverse Dean−Stark trap was dissolved 3-(5-oxo-4phenyl-2-(trifluoromethyl)-2,5-dihydrooxazol-2-yl)butanal (7) (5.0 g, 16.7 mmol, 1.0 equiv) in 100 mL of CHCl3. Propane-1,3-diol was then added dropwise (6.32 g, 6.0 mL, 83.5 mmol, 5.0 equiv) with PTSA (0.16 g, 0.84 mmol, 0.05 equiv). The reaction mixture was vigorously stirred and refluxed during 1 h 30. Without cooling, the reaction mixture was treated with 100 mL of NaHCO3. The organic layer was then dried over MgSO4, filtered, and removed under reduced pressure to give a yellow oil. The crude product was purified via flash chromatography (petroleum ether/ethyl acetate, 95:5) to give 9b as a colorless liquid in 90% yield (5.34 g, 15.03 mmol). Rf = 0.3 (petroleum ether/ethyl acetate, 95:5). 1H NMR (600 MHz, CDCl3, ppm): δ = 1.17 (d, J = 7 Hz, 3 Hdia;1), 1.22 (d, J = 7 Hz, 3 Hdia;2), 1.32 (dtt, J = 1.5, 2.5, 13.5 Hz, 1 H), 1.45 (ddd, J = 4, 9.5, 14 Hz, 1 H; dia 2), 1.56 (ddd, J = 4, 9.5, 14 Hz, 1 H; dia 1), 1.85 (ddd, J = 4, 6.5, 14 Hz, 1 H), 2.04 (m, 1 H), 2.72 (dqd, J = 4, 7, 10.5 Hz, 1 H; dia 2), 2.79 (m, 1 H; dia 1), 3.72 (m, 2 H), 4.05 (m, 2H), 4.61(m, 1H), 7.51 (t, J = 8 Hz, 2H), 7.62 (tt, J = 1.5, 8 Hz, 1H), 8.41 (dd, J = 1.5, 8 Hz, 2 H). 13C NMR (150 MHz, CDCl3, ppm): δ = 13.8 (dia 1), 14.5 (dia 2), 25.7, 33.2 (dia 1), 33.4 (dia 2), 35.5 (dia 2), 35.6 (dia 1), 66.99, 67.03, 67.1, 100.2 (dia 1), 100.3 (dia 2), 103.0 (q, J = 29.5 Hz), 103.1 (q, J = 29.5 Hz), 122.2 (q, J = 287 Hz), 127.7, 129.1, 129.3, 133.8, 160.0 (dia 1), 160.4 (dia 2), 162.9 (dia 2), 163.1 (dia 1). 19F NMR (250 MHz, CDCl3, ppm): δ = −75.67, − 75.6. IR (ν): 1798, 1614, 1379, 1289, 1252, 1235, 1198, 1170 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C17H19NO4F3 358.1266, found 358.1259. 3′-Phenyl-7a′-(trifluoromethyl)tetrahydro-2′H-spiro[[1,3]dioxolane-2,5′-pyrrolo[2,1-b]oxazol]-2′-one (12a) and 6-Phenyl-8-(trifluoromethyl)-1,4-dioxa-7-azaspiro[4.5]dec-6-ene (11a). A solution of 8a (300 mg, 0.91 mmol) was diluted in 91 mL of dry acetonitrile. The reaction mixture was then transferred into quartz tubes and bubbled during 20 min with argon and then irradiated during 4 h 30 at λ = 300 nm. The solution was evaporated under vacuum and the crude product was purified via flash chromatography 1872


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137.2, 168.8. 19F NMR (235 MHz, CDCl3, ppm): δ = −76.59 (d, J = 8.0 Hz). IR (ν): 1644, 1385, 1346, 1312, 1274, 1186 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H17NO2F3 300.1211, found 300.1212. 6-Methyl-3-phenyl-6a-(trifluoromethyl)tetrahydrospiro[cyclopenta[b]furan-4,2′- [1,3]dioxolan]-2(5H)-one (16a) and 9Methyl-6-phenyl-8-(trifluoromethyl)-1,4-dioxa-7-azaspiro[4.5]dec-6-ene (15a). A solution of 9a (1.03 g, 3.0 mmol) was diluted in 150 mL of dry acetonitrile. The reaction mixture was then transferred into quartz tubes and bubbled with argon during 20 min and then irradiated during 1 h at λ = 300 nm. The solution was then heated at 65 °C during 2 h and solvent was evaporated under reduced pressure. The crude product was purified via flash chromatography (petroleum ether/dichloromethane, 60:40) to give the 6-methyl-3-phenyl-6a(trifluoromethyl)tetrahydrospiro[cyclopenta[b]furan-4,2′-[1,3]dioxolan]-2(5H)-one (16a) as a white powder in 34% yield (355 mg, 1.02 mmol) and 9-methyl-6-phenyl-8-(trifluoromethyl)-1,4-dioxa-7azaspiro[4.5]dec-6-ene (15a) as a white powder in 25% yield (263 mg,0.42 mmol), (dia1: 14%, 48 mg, 0.42 mmol; dia2: 11%, 115 mg, 0.33 mmol). Compound 16a. Rf = 0.51 (petroleum ether/dichloromethane, 60:40), Rf (dia 1) = 0.84 (petroleum ether/ethyl acetate, 80:20), Rf (dia 2) = 0.7 (petroleum ether/ethyl acetate, 80:20). Melting range = 93−95 °C. 1H (500 MHz, CDCl3, dia 1, ppm): δ = 1.24 (d, J = 7.5 Hz, 3 H), 1.96 (dd, J = 6.5, 13.5 Hz, 1 H), 2.51 (dd, J = 7.5, 13.5 Hz, 1 H), 2.91 (h, J = 6.5, 7.5 Hz, 1 H), 3.73 (td,J = 6.5,8.0 Hz,1H), 3.78(td,J = 3.5, 7.0 Hz, 1 H), 3.86 (q, J = 7.0, 8.0 Hz, 1 H), 3.94 (ddd, J = 3.5, 6.5, 8.0 Hz, 1 H), 5.29 (s, 1 H), 7.31 (t, J = 7.5 Hz, 1 H), 7.38 (t, J = 7.5, 8.0 Hz, 2 H), 7.62 (d, J = 8.0 Hz, 2 H). 1H NMR (500 MHz, CDCl3, dia 2, ppm): δ = 1.32 (dq, J = 2.0, 7.0 Hz, 3 H), 2.28 (d, J = 11.0 Hz, 2H), 2.68 (m,1H), 3.69 (td, J = 7.0, 11.0 Hz, 1H), 3.91 (m, 2H), 4.04 (td, J = 2.5, 6.0, 5.5 Hz, 1H), 5.31 (s, 1 H), 7.30 (t, J = 7.5 Hz, 1 H), 7.37 (t, J = 7.5 Hz, 2 H), 7.68 (d, J = 7.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3, dia 1, ppm): δ = 14.2, 34.3, 40.7, 58.9, 63.6, 66.2, 99.6 (q, J = 33.0 Hz), 121.0, 123.1 (q, J = 286.5 Hz), 126.5, 129.1, 128.6, 134.9, 172.5. 13C NMR (125 MHz, CDCl3, dia 2, ppm): δ = 12.9, 40.6, 42.2, 57.2, 64.5, 66.0, 98.6 (q, J = 32.0 Hz), 120.1, 122.8 (q, J = 287.0 Hz), 126.1, 127.9, 128.5, 134.6, 172.2. 19F NMR (235 MHz, CDCl3, dia 1, ppm): δ = −83.36. 19F NMR (235 MHz, CDCl3, dia 2, ppm): δ = −79.10. IR (ν): 1959, 1812, 1383, 1274, 1213, 1021 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H17NO4F3 344.1110, found 344.1110. Compound 15a. Rf = 0.36 (petroleum ether/dichloromethane, 60:40). Melting range = 65−67 °C. 1H NMR (600 MHz, CDCl3, ppm): δ = 1.21 (dd, J = 1.5, 6.5 Hz, 3 H), 1.73 (t, J = 13.5 Hz, 1 H), 1.96 (dd, J = 3.5, 13.5 Hz, 1 H), 2.29 (ddqd, J = 3.5, 6.5, 10.0, 13.5 Hz, 1 H), 3.67 (q, J = 6.5, 7.5 Hz, 1 H), 3.81 (dq, J = 8.0, 10.0 Hz, 1 H), 3.85 (ddd, J = 5.0, 6.5, 8.0 Hz, 1 H), 3.90 (q, J = 6.5, 7.5, 8.0 Hz, 1 H), 3.97 (td, J = 5.0, 6.5, 7.5 Hz, 1 H), 7.35 (m, 3 H), 7.58 (m, 2 H). 13C NMR (150 MHz, CDCl3, ppm): δ = 19.5, 27.4, 40.5, 65.1, 65.9, 67.1 (q, J = 27.0 Hz), 103.4, 125.8 (q, J = 281.0 Hz), 128.1, 128.7, 129.3, 138.0, 170.5. 19F NMR (235 MHz, CDCl3, ppm): δ = −72.37 (d, J = 7.5 Hz), − 72.04 (d, J = 9 Hz). IR (ν): 1805, 1316, 1171 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H17NO2F3 300.1211, found 300.1212. 6-Methyl-3-phenyl-6a-(trifluoromethyl)tetrahydrospiro[cyclopenta[b]furan-4,2′- [1,3]dioxan]-2(5H)-one (16b) and 10Methyl-7-phenyl-9-(trifluoromethyl)-1,5-dioxa-8-azaspiro[5.5]undec-7-ene (15b). A solution of 9b (1.1 g, 3.22 mmol) was diluted in 150 mL of dry acetonitrile. The reaction mixture was then transferred into quartz tubes and bubbled with argon during 20 min and then irradiated during 1 h at 300 nm. The solution was then heated at 65 °C during 2 h and solvent was evaporated under reduced pressure. The crude product was purified via flash chromatography (petroleum ether/dichloromethane, 70:30 → 60:40) to give 6-methyl3-phenyl-6a-(trifluoromethyl)tetrahydrospiro[cyclopenta[b]furan-4,2′[1,3]dioxan]-2(5H)-one (16b) as a white powder in 14% yield (150 mg, 0.46 mmol) and 10-methyl-7-phenyl-9-(trifluoromethyl)-1,5dioxa-8-azaspiro[5.5]undec-7-ene (15b) as a white powder in 60% yield (560 mg, 1.93 mmol).

(petroleum ether/dichloromethane, 50:50) to give 3′-phenyl-7a′(trifluoromethyl)tetrahydro-2′H-spiro[[1,3]dioxolane-2,5′-pyrrolo[2,1-b]oxazol]-2′-one (12a) as a white powder in 33% yield (100 mg, 0.30 mmol) and 6-phenyl-8-(trifluoromethyl)-1,4-dioxa-7azaspiro[4.5]dec-6-ene (11a) as a white crystalline powder in 22% yield (57 mg, 0.20 mmol). Compound 12a. Rf = 0.58 (petroleum ether/dichloromethane, 50:50). Melting range = 79−81 °C. 1H NMR (600 MHz, CDCl3, ppm): δ = 2.22−2.44 (m, 3 H), 2.59−2.69 (m, 1 H), 3.78−4.03 (m, 4 H), 5.27 (s, 1 H), 7.31−7.36 (m, 1 H), 7.40 (t, J = 7.6 Hz, 2 H), 7.67 (d,J = 8.1 Hz,2H). 13C NMR (151 MHz, CDCl3, ppm): δ = 29.5, 33.3, 57.8, 64.2, 65.9, 98.0 (q, J = 34.3 Hz), 122.0, 122.5 (q, J = 285.2 Hz), 125.9, 127.9, 128.4, 134.4, 172.3. 19F NMR (235 MHz, CDCl3, ppm): δ = −83.88. IR (ν): 1961, 1809, 1655, 1333, 1282, 1204, 1179 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H15NO4F3 330.0954, found 330.0955. Compound 11a. Rf = 0.33 (petroleum ether/dichloromethane, 50:50). Melting range = 90−91 °C. 1H NMR (600 MHz, CDCl3, ppm): δ = 1.94 (td, J = 13.2, 3.6 Hz, 1 H), 2.01−2.20 (m, 3 H), 3.68 (q, J = 7.2 Hz, 1 H), 3.84−4.02 (m, 3 H), 4.11 (dtd, J = 11.0, 7.7, 4.4 Hz, 1 H), 7.34−7.41 (m, 3 H), 7.57−7.63 (m, 2 H). 13C NMR (151 MHz, CDCl3, ppm): δ = 20.2, 31.1, 60.6 (q, J = 29.3 Hz), 64.9, 65.8, 102.3, 125.3 (q, J = 279.3 Hz), 127.2, 127.9, 128.5, 129.2, 138.0, 171.1. 19 F NMR (235 MHz, CDCl3, ppm): δ = −76.83 (d, J = 7.7 Hz). IR (ν): 1654, 1367, 1275, 1184, 1128 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C14H14NO2F3Na 308.0874, found 308.0880. 7-Phenyl-9-(trifluoromethyl)-1,5-dioxa-8-azaspiro[5.5]undec-7-ene (11b) via the Intermediary of 5-(Trifluoromethyl)6-oxa-8-azaspiro[bicyclo[3.2.1]octane-2,2′-[1,3]dioxan]-7-one (10b). A solution of 8b (1.1 g, 3.22 mmol) was diluted in 150 mL of dry acetonitrile. The reaction mixture was then transferred into quartz tubes and bubbled with argon during 20 min and then irradiated during 1 h at λ = 300 nm. The solution was then heated at 65 °C during 2 h and solvent was evaporated under reduced pressure. The crude product was purified via flash chromatography (petroleum ether/ethyl acetate, 60:40) to give 7-phenyl-9-(trifluoromethyl)-1,5dioxa-8-azaspiro[5.5]undec-7-ene (11b) as a white crystalline powder in 83% yield (802 mg, 2.67 mmol). A supplementary procedure enabled the detection of the intermediate 10b. Compound 8b (40 mg, 0.12 mmol) was diluted in 12 mL of dry acetonitrile. The solution was transferred in a quartz tube, bubbled with argon during 20 min and irradiated during 30 min. The solvent was then evaporated and the crude product was diluted in n-hexane to achieve a recrystallization. The precipitated compound 10b was retrieved by filtration as a white crystalline powder in 38% yield (15 mg, 0.046 mmol). The recrystallization solvent was evaporated under reduced pressure and the crude product was purified via flash chromatography (petroleum ether/ethyl acetate, 90:10) to give 11b as a white crystalline solid in 32% yield (12.7 mg, 0.038 mmol). Compound 10b. Rf = 0.20 (petroleum ether/ethyl acetate, 90:10). Decomposition range = 112−113 °C. 1H NMR (600 MHz, CDCl3, ppm): δ = 1.26−1.34 (m, 1 H), 1.61 (ddt, J = 13.3, 11.7, 6.2 Hz, 1 H), 1.92 (ddd, J = 14.8, 12.3, 6.5 Hz, 1 H), 2.18 (td, J = 13.0,6.1 Hz, 1 H), 2.25−2.32 (m, 1 H), 3.04−3.10 (m, 1 H), 3.32 (s, 1 H), 3.77−3.83 (m, 2 H), 3.93 (dtd, J = 15.0, 11.8, 3.2 Hz, 2 H), 7.36 (d, J = 2.3 Hz, 3 H), 7.76−7.85 (m, 2 H). 13C NMR (151 MHz, CDCl3, ppm): δ = 23.7, 24.6, 25.9, 59.8, 60.7, 70.6, 91.8 (q, J = 34.3 Hz), 94.2, 121.8 (d, J = 281.0 Hz), 127.2, 128.2, 128.5, 132.1, 170.7. 19F NMR (235 MHz, CDCl3): δ = −76.60 (d, J = 7.8 Hz). IR (ν): 3312, 1948, 1811, 1710, 1604, 1349, 1271, 1245 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C16H16F3NO4Na 366.0929, found 366.0931. Compound 11b. Rf = 0.21 (petroleum ether/ethyl acetate, 90:10). Melting range = 124−125 °C. 1H NMR (600 MHz, CDCl3, ppm): δ = 1.48 (dp, J = 2.0, 2.5, 13.5 Hz, 1 H), 1.77 (td, J = 3.5, 13.5 Hz, 1 H), 1.90 (tdd, J = 3.5, 10.5, 13.5 Hz, 1 H), 2.07 (dq, J = 3.5, 5, 13.5 Hz, 1 H), 2.27 (qt, J = 5.5, 12.5, 13.5 Hz, 1 H), 2.94 (dt, J = 5.0, 13.5 Hz, 1 H), 3.91 (ddt, J = 2.0, 5.5, 12 Hz, 1 H), 3.99 (ddt, J = 2.0, 5.5, 12 Hz, 1 H), 4.09 (m, 3 H), 7.37 (m, 3 H), 8.01 (dd, J = 2.0, 8.0 Hz, 2 H). 13C NMR (125 MHz, CDCl3, ppm): δ = 18.7 (m), 24.4, 25.0, 59.7, 59.8, 60.8 (q, J = 29.0 Hz), 93.9, 125.5 (q, J = 279 Hz), 127.7, 129.4, 129.6, 1873


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The Journal of Organic Chemistry Compound 16b. Rf = 0.74 (petroleum ether/dichloromethane, 60:40). Melting range = 126−128 °C. 1H NMR (500 MHz, CDCl3, ppm): δ = 1.23 (d, J = 7.0 Hz, 3 H), 1.37 (dp, J = 3.5, 13.5 Hz, 1 H), 1.78 (dd, J = 11.0, 13.0 Hz, 1 H), 1.87 (m, 1 H), 2.26 (dd, J = 7.0, 13.0 Hz, 1 H), 2.92 (dp, J = 7.0, 11.0 Hz, 1 H), 3.47 (td, J = 3.5, 11.0 Hz, 1 H), 3.70 (dtd, J = 1.5, 4.5, 11.0 Hz, 1 H), 3.80 (dtd, J = 1.5, 4.5, 11.0 Hz, 1 H), 4.17 (td, J = 3.5, 11.0 Hz, 1 H), 5.23 (s, 1 H), 7.33 (t, J = 7.5 Hz, 1 H), 7.41 (t, J = 7.5 Hz, 2 H), 7.65 (d, J = 7.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3, ppm): δ = 13.7, 24.2, 34.4, 41.4, 59.9, 60.0, 63.5, 100.5 (q, J = 33 Hz), 122.1, 123.3 (q, J = 285.5 Hz), 126.6, 128.3, 128.8, 135.5, 172.5. 19F NMR (235 MHz, CDCl3, ppm): δ = −82.29. IR (ν): 1798, 1368, 1284, 1252, 1215, 1178, 1143 cm−1. HRMS (ESITOF) m/z: [M + H]+ calcd for C17H19NO4F3 358.1266, found 358.1270. Compound 15b. Rf = 0.31 (petroleum ether/dichloromethane, 60:40). Melting range = 148−151 °C. 1H NMR (500 MHz, CDCl3, ppm): δ = 1.23 (dd, J = 1.5, 6.5 Hz, 3 H), 1.47 (t, J = 12.5, 14.0 Hz, 1 H), 1.47 (dt, J = 2.0, 13.0 Hz, 1 H), 2.16 (ddtd, J = 3.5, 6.5, 13.0, 16.5 Hz, 1 H), 2.28 (qt, J = 5.5, 13.0 Hz, 1 H), 2.89 (dd, J = 4.0, 14.0 Hz, 1 H), 3.79 (dq, J = 8.0, 10.0 Hz, 1 H), 3.90 (ddt, J = 2.0, 5.5, 12.0 Hz, 1 H), 3.99 (ddt, J = 2.0, 2.5, 12.0 Hz, 1 H), 4.07 (td, J = 3.0, 12.0, 13.0 Hz, 1 H), 4.11 (td, J = 3.0, 12.0, 13.0 Hz, 1 H), 7.36 (m, 3 H), 8.01 (dd, J = 2.0, 8.0 Hz, 2 H). 13C NMR (125 MHz, CDCl3, ppm): δ = 19.7 (q, J = 2.5 Hz), 25.1, 25.7, 34.0, 59.8, 59.9, 67.4 (q, J = 27.0 Hz), 94.8, 126.0 (q, J = 280.5 Hz), 127.7, 127.8, 129.5, 129.6, 136.9, 168.0. 19 F NMR (235 MHz, CDCl3, ppm): δ = −72.55 (d, J = 8.0 Hz, dia 1), − 71.75 (d, J = 9.0 Hz, dia 2). IR (ν): 1966, 1911, 1646, 1373, 1260, 1192 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H19NO2F3 314.1368, found 314.1363.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02810. X-ray crystallographic data (CIF) Spectra (1H, 13C, and 19F NMR, HRMS, UV), X-ray structure analysis reports, and computational details for the reaction of 8a and 8b (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *Phone: + 33 3 26 91 33 10. E-mail: norbert.hoff[email protected]. ORCID

Manabu Abe: 0000-0002-2013-4394 Norbert Hoffmann: 0000-0002-8615-7476 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful for financial support from the Université de Reims Champagne-Ardenne and the French Ministry of Higher Education Research and Innovation. We thank Dr. Dominique Harakat for particular help with the recording of HRMS spectra.

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REFERENCES

(1) Special Issue: Photochemistry in Organic Synthesis: Chem. Rev. 2016, 116 (17). (2) Hoffmann, N. Chem. Rev. 2008, 108, 1052−1103. Bach, T.; Hehn, J. P. Angew. Chem., Int. Ed. 2011, 50, 1000−1045. (3) Ciana, C.-L.; Bochet, C. G. Chimia 2007, 61, 650−654. Glusac, K. Nat. Chem. 2016, 8, 734−735. 1874


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