Thomas J.
Cogswell
a,
Craig S.
Donald
b,
De-Liang
Long‡
a and
Rodolfo
Marquez§
*a
aSchool of Chemistry, University of Glasgow, Glasgow, G12 8QQ, UK. E-mail: rudi.marquez@glasgow.ac.uk; Fax: +44 (0)141 330 4888; Tel: +44 (0)141 330 5953
bOncology iMed, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
First published on 29th August 2014
The diastereoselective synthesis of fluorinated δ-lactams has been achieved through an efficient five step process. The route can tolerate a range of functionalities, and provides a quick route for the generation of new fluorinated medicinal building blocks.
δ-Lactams on the other hand are also present widely in medicinal chemistry and natural systems. For instance, aripiprazole 1 is used currently for the treatment of schizophrenia and bipolar disorders (Fig. 1).3
Thus, it is not surprising that considerable time and efforts have been directed towards the synthesis of fluorinated δ-lactams.4–6 However to date, there are a relatively small number of examples and few general routes available to enable synthesis of compound libraries to drive structure–activity relationship understanding in medicinal chemistry programmes.
Herein, we would like to report a short and efficient route to the synthesis of fluorinated δ-lactams starting from commercial aldehydes. The methodology is amenable for the generation of a wide range of δ-lactams, and has the potential to allow entry into several different classes of N-heterocyclic compounds.
Amide 5 was then treated with a range of metathesis catalysts in an attempt to induce ring closure (Scheme 2), however only a complex mixture of cross metathesis products resulted, with no desired cyclised product 6 being detected.
The lack of cyclisation could be attributed to the interaction of the ruthenium catalyst with the amide group which prevents the ring closing metathesis from taking place, in a situation similar to that reported by Vilar and co-workers.8
To test this hypothesis, the route was altered to incorporate a protecting group on the amide to prevent the amide from interacting with the Ru catalyst. The protecting group of choice was the p-methoxybenzyl group due to its electron donating properties, and the ease of removal via oxidative cleavage.9
Thus, reaction of p-methoxybenzylamine with benzaldehyde yielded the corresponding imine which upon allyl Grignard addition produced the secondary amine 7a in near quantitative yield. HBTU promoted coupling between the amine 7a and 2-fluoroacrylic acid 4 and then proceeded to generate the desired amide 8a in good yield.
Gratifyingly, PMB protection of the amide unit allowed the ring closing metathesis reaction to proceed smoothly to yield the unsaturated lactam 9a in quantitative yield (Table 1).
R | Yield | Yield | Yield | |||
---|---|---|---|---|---|---|
Ph | 95% | 7a | 63% | 8a | Quant | 9a |
4-MeOPh | 80% | 7b | 66% | 8b | Quant | 9b |
4-CF3Ph | 66% | 7c | 45% | 8c | Quant | 9c |
1-Naphthyl | 99% | 7d | 31% | 8d | Quant | 9d |
4-BrPh | 97% | 7e | 54% | 8e | 99% | 9e |
i-Butyl | 76% | 7f | 74% | 8f | 85% | 9f |
Cyclohexyl | 74% | 7g | 70% | 8g | 89% | 9g |
2-Furyl | 83% | 7h | 28% | 8h | 64% | 9h |
N-Ts 2-pyrrole | 85% | 7i | 50% | 8i | 77% | 9i |
2-Pyridyl | 73% | 7j | 68% | 8j | — | 9j |
With the benzaldehyde example working efficiently, the scope of the methodology was explored (Table 1). Electron donating and electron withdrawing substituents on the aromatic ring were both tested with good results in all cases through the four step sequence. The electron withdrawing analogue being slightly less efficient in the first three steps, however, the RCM reaction produced the desired unsaturated lactam 9c in quantitative yield.
Aliphatic substrates are also well tolerated, and afforded the corresponding fluorinated lactams 9f, 9g cleanly and in good yield over the 4 step sequence.
Finally, furan, pyrrole and pyridine frameworks were also explored due to their widespread use in medicinal and biological chemistry. Furfural and N-tosylpyrrole carboxaldehyde proceeded to generate the structurally interesting fluorinated δ-lactams 9h, 9i in good yield. In the case of the pyridine unit, the amino allylation and amide coupling proceeded in reasonable yields, affording intermediates 7j and 8j respectively. Unfortunately, the ring closing metathesis failed to generate the desired fluorinated δ-lactam 9j under any of the conditions attempted. This was rationalised in the same manner as the previous example (Scheme 2), where an unprotected nitrogen atom was thought to bind to the Ru catalyst.
With the fluorinated ring system in place, the removal of the p-methoxybenzyl protecting group and reduction of the olefin unit were explored. Removal of the PMB group was achieved with cerium ammonium nitrate to yield the desired fluoro-pyridones 10a–g in variable yields (Table 2). Unfortunately, treatment of the furyl and pyrrole substituted pyridones 9h–i with CAN failed to yield the desired unprotected pyridones, resulting instead in substrate decomposition.
Hydrogenation of the fluoro-olefin unit, on the other hand, proceeded in near quantitative yield in most cases, and with complete diastereoselectivity to yield the desired fluorinated δ-lactams 11a–g. The only exception was the brominated analogue 10e, which unsurprisingly yielded the unbrominated lactam 11a upon hydrogenation in excellent yield.
The syn selectivity of hydrogenation, and hence the stereochemistry of the newly formed C3 stereocentre, is dictated by the C6 substituent. The relative stereochemistry was corroborated by X-ray crystallography (Fig. 2).10
The bromo-lactam intermediate 10e, on the other hand, presented us with an opportunity to further explore the scope of the fluoro-lactam intermediates as medicinal chemistry building blocks. Thus treatment of fluoro-lactam 10e under Suzuki–Miyaura conditions with phenylboronic acid generated the tricyclic unit 12 in near quantitative yield.11
Alkene reduction under standard conditions then generated the desired fluoro-lactam unit 13 in excellent yield and with complete diastereocontrol (Scheme 3).
1H (CDCl3, 400 MHz) δ: 7.27–7.15 (5H, m), 5.68–5.63 (1H, m), 5.06–5.00 (2H, m), 3.91 (1H, dd, JHH = 8.0, 5.2 Hz) 2.40–2.27 (2H, m), 1.60 (2H, br s). 13C (CDCl3, 125 MHz) δ: 145.8, 135.4, 128.4, 127.9, 126.4, 117.7, 55.4, 44.2.
1H (CDCl3, 400 MHz) δ: 11.51 (1H, br s), 5.92 (1H, dd, JHF = 42.8, JHH = 3.6 Hz), 5.52 (1H, dd, JHF = 12.4, JHH = 3.2 Hz). 19F (CDCl3, 470 MHz) δ: −118.3. 13C (CDCl3, 125 MHz) δ: 165.4 (d, JCF = 46.3 Hz), 151.3 (d, JCF = 323.8 Hz), 105.2 (d, JCF = 18.8 Hz).
1H (CDCl3, 400 MHz) δ: 7.28–7.16 (5H, m), 6.48 (1H, br s), 5.66–5.55 (2H, m), 5.09–5.03 (4H, m), 2.55 (2H, t, JHH = 6.8 Hz). 19F (CDCl3, 470 MHz) δ: −121.3. 13C (CDCl3, 125 MHz) δ: 158.8 (d, JCF = 30.0 Hz), 156.2 (d, JCF = 268.8 Hz) 140.8, 133.4, 128.8, 127.7, 126.5, 118.3, 99.1 (d, JCF = 15.0 Hz), 52.6, 40.3. m/z [CI (+ve)] 220.3 [M + H]+, HRMS found [M + H]+ 220.1135, C13H15FNO requires 220.1138. IR (thin film) νmax = 3338, 1651, 1529, 1190 cm−1.
1H (CDCl3, 400 MHz) δ: 10.01 (1H, s), 7.83 (2H, d, JHH = 8.3 Hz), 7.65 (1H, dd, JHH = 3.0, 1.8 Hz), 7.35 (2H, d, JHH = 8.3 Hz), 7.12 (1H, dd, JHH = 3.7, 1.8 Hz), 6.43 (1H, br appt, JHH = 3.4 Hz), 2.45 (3H, s). 13C (CDCl3, 125 MHz) δ: 178.9, 145.9, 135.3, 133.6, 130.1, 129.5, 127.6, 124.4, 112.4, 21.7.
1H (CDCl3, 400 MHz) δ: 7.40–7.36 (4H, m,), 7.30–7.28 (1H, m), 7.20 (2H, d, JHH = 8.6 Hz), 6.88 (2H, d, JHH = 8.6 Hz), 5.75–5.70 (1H, m), 5.11–5.70 (2H, m), 3.83 (3H, s), 3.71 (1H, dd, JHH = 7.8, 5.9 Hz), 3.64 (1H, d, JHH = 13.2 Hz), 3.49 (1H, d, JHH = 13.2 Hz,), 2.44–2.41 (2H, m), 1.73 (1H, br s). 13C (CDCl3, 125 MHz) δ: 158.5, 143.9, 135.5, 132.8, 129.3 (2C), 128.4 (2C), 127.3 (2C), 127.0 (2C), 117.5, 113.7, 61.5, 55.3, 50.8, 43.1.
1H (CDCl3, 400 MHz) δ: 7.30 (2H, d, JHH = 8.8 Hz), 7.19 (2H, d, JHH = 8.6 Hz), 6.92 (2H, d, JHH = 8.8 Hz), 6.87 (2H, d, JHH = 8.6 Hz), 5.75–5.68 (1H, m), 5.12–5.04 (2H, m), 3.85 (3H, s) 3.82 (3H, s), 3.68–3.60 (2H, m), 3.47 (1H, d, JHH = 12.9 Hz), 2.43–2.39 (2H, m). 13C (CDCl3, 125 MHz) δ: 158.6, 158.5, 135.9, 135.6 (2C), 132.8, 129.3 (2C), 128.3 (2C), 117.4, 113.7 (2C), 60.81, 55.3, 55.2, 50.7, 43.2.
1H (CDCl3, 400 MHz) δ: 7.62 (2H, d, JHH = 8.2 Hz), 7.51 (2H, d, JHH = 8.2 Hz), 7.18 (2H, d, JHH = 8.8 Hz), 6.88 (2H, d, JHH = 8.8 Hz), 5.75–5.65 (1H, m), 5.12–5.08 (2H, m), 3.83 (3H, s), 3.77 (1H, dd, JHH = 7.6, 5.6 Hz), 3.64 (1H, d, JHH = 13.2 Hz), 3.45 (1H, d, JHH = 13.2 Hz), 2.45–2.34 (2H, m). 19F (CDCl3, 377 MHz) δ: −62.3. 13C (CDCl3, 125 MHz) δ: 158.7, 148.2, 134.8, 132.4, 129.8 (2C), 127.7 (2C), 125.7, 125.4 (2C), 125.3, 118.2, 113.8 (2C), 61.2, 55.3, 44.2, 33.6. m/z [CI (+ve)] 336.1 [M + H]+. HRMS found [M + H]+ 336.1572, C19H21F3NO requires 336.1575. IR (thin film) νmax = 2935, 1612, 1512, 1323, 1246, 1120, 1066 cm−1.
1H (CDCl3, 400 MHz) δ: 8.10 (1H, appd, JHH = 7.4 Hz), 7.81–7.79 (1H, m), 7.72–7.67 (2H, m), 7.44–7.38 (3H, m), 7.09 (2H, d, JHH = 8.6 Hz), 6.76 (2H, d, JHH = 8.6 Hz), 5.75–5.67 (1H, m), 5.05–4.97 (2H, m), 3.71 (3H, s), 3.60 (1H, d, JHH = 13.0 Hz), 3.44 (1H, d, JHH = 13.0 Hz), 2.59–2.54 (1H, m), 2.41–2.35 (1H, m). 13C (CDCl3, 125 MHz) δ: 158.7, 139.7, 138.9, 135.8, 134.1, 132.9, 131.7, 129.4 (2C), 129.0, 127.4, 125.7, 125.3, 123.9, 123.1, 117.7, 113.8 (2C), 56.9, 55.4, 51.1, 42.2. m/z [CI (+ve)] 318.2 [M + H]+, HRMS found [M + H]+ 318.1862, C22H24NO requires 318.1858. IR (thin film) νmax = 2960, 1511, 1246, 1035 cm−1.
1H (CDCl3, 500 MHz) δ: 7.48 (2H, d, JHH = 8.4 Hz), 7.27 (2H, d, JHH = 8.4 Hz), 7.15 (2H, d, JHH = 9.1 Hz), 6.87 (2H, d, JHH = 9.1 Hz), 5.72–5.63 (1H, m), 5.10–5.05 (2H, m), 3.82 (3H, s), 3.66 (1H, dd, JHH = 7.8, 6.3 Hz), 3.61 (1H, d, JHH = 13.1 Hz), 3.46 (1H, d, JHH = 13.1 Hz), 2.40–2.35 (2H, m). 13C (CDCl3, 125 MHz) δ: 158.7, 143.3, 135.1, 132.6, 131.6 (2C), 129.3 (2C), 129.1 (2C), 120.4, 117.9, 113.9 (2C), 60.7, 55.3, 50.9, 42.7. m/z [CI (+ve)] 345.8 M+, HRMS found [M + H]+ 346.0804, C18H2179BrNO requires 346.0807. IR (thin film) νmax = 2945, 2835, 1511, 1245, 1035, 1009 cm−1.
1H (CDCl3, 400 MHz) δ: 7.26 (2H, d, JHH = 8.8 Hz), 6.86 (2H, d, JHH = 8.8 Hz), 5.82–5.70 (1H, m), 5.14–5.00 (2H, m), 3.81 (3H, s), 3.73 (1H, quint, JHH = 6.4 Hz), 2.70–2.65 (1H, m), 2.25–2.03 (2H, m), 1.62 (1H, appsept, JHH = 6.8 Hz), 1.46–1.23 (2H, m), 0.90 (3H, d, JHH = 6.6 Hz), 0.87 (3H, d, JHH = 6.6 Hz). 13C (CDCl3, 100 MHz) δ: 158.5, 135.8, 133.0, 129.3 (2C), 118.7, 113.7 (2C), 55.3, 54.0, 50.5, 41.2, 38.6, 24.7, 22.5. m/z [CI (+ve)] 248.2 [M + H]+, HRMS found [M + H]+ 248.2018, C16H26NO requires 248.2014. IR (thin film) νmax = 2953, 2906, 1612, 1512, 1464, 1246 cm−1.
1H (CDCl3, 400 MHz) δ: 7.26 (2H, d, JHH = 8.6 Hz), 6.87 (2H, d, JHH = 8.6 Hz), 5.85–5.75 (1H, m), 5.11–5.06 (2H, m), 3.82 (3H, s), 3.71 (2H, s), 2.42–2.38 (1H, m), 2.32–2.26 (1H, m), 2.16–2.09 (1H, m), 1.81–1.70 (4H, m), 1.47–1.43 (1H, m), 1.31–1.18 (4H, m,), 1.10–1.00 (2H, m). 13C (CDCl3, 125 MHz) δ: 158.5, 136.8, 133.3, 129.3 (2C), 116.8, 113.7 (2C), 61.1, 55.3, 51.3, 40.6, 35.3, 29.4, 28.9, 26.8, 26.7, 26.7. m/z [CI (+ve)] 274.2 [M + H]+, HRMS found [M + H]+ 274.2171, C18H28NO requires 274.2168. IR (thin film) νmax = 2924, 1511, 1246, 1037 cm−1.
1H (CDCl3, 400 MHz) δ: 7.42 (1H, dd, JHH = 1.8, 0.8 Hz), 7.23 (2H, d, JHH = 8.7 Hz), 6.88 (2H, d, JHH = 8.7 Hz), 6.36 (1H, dd, JHH = 3.7, 1.8 Hz), 6.21 (1H, d, JHH = 3.7 Hz), 5.79–5.62 (1H, m), 5.14–5.06 (2H, m), 3.83 (3H, s), 3.79 (1H, t, JHH = 6.8 Hz), 3.72 (1H, d, JHH = 13.0 Hz), 3.56 (1H, d, JHH = 13.0 Hz), 2.58–2.53 (2H, m). 13C (CDCl3, 125 MHz) δ: 158.6, 156.3, 141.5, 134.9, 132.4, 129.4 (2C), 117.5, 113.8 (2C), 109.9, 106.6, 55.3, 54.7, 50.5, 39.3. m/z [CI (+ve)] 258.2 [M + H]+, HRMS found [M + H]+ 258.1492, C16H20NO2 requires 258.1494. IR (thin film) νmax = 2930, 2850, 1511, 1441, 1246, 1035 cm−1.
1H (CDCl3, 500 MHz) δ: 7.62 (2H, d, JHH = 8.3 Hz), 7.36 (1H, dd, JHH = 3.2, 1.7 Hz), 7.25 (2H, d, JHH = 8.3 Hz), 7.15 (2H, d, JHH = 8.6 Hz), 6.84 (2H, d, JHH = 8.6 Hz), 6.35–6.33 (1H, m), 6.30 (1H, t, JHH = 3.3 Hz), 5.73–5.63 (1H, m), 5.05–4.98 (2H, m), 4.22 (1H, dd, JHH = 7.3, 5.1 Hz), 3.84 (3H, s), 3.43 (1H, d, JHH = 12.6 Hz), 3.25 (1H, d, JHH = 12.6 Hz), 2.47–2.30 (2H, m), 2.41 (3H, s). 13C (CDCl3, 125 MHz) δ: 158.6, 144.9, 137.6, 136.7, 135.0, 132.6, 129.9 (2C), 129.1 (2C), 126.7 (2C), 123.1, 117.5, 114.1 (2C), 112.7, 111.6, 55.3, 54.0, 50.1, 40.7, 21.7. m/z [ESI] 433.1 [M + Na]+, HRMS found [M + Na]+ 433.1539, C23H26N2O3SNa requires 433.1556. IR (thin film) νmax = 2975, 1512, 1247, 1172 cm−1.
1H (CDCl3, 400 MHz) δ: 8.51 (1H, dq, JHH = 4.8, 0.9 Hz), 7.58 (1H, td, JHH = 7.7, 1.8 Hz), 7.30 (1H, d, JHH = 7.7 Hz), 7.12 (2H, d, JHH = 8.6 Hz), 7.08 (1H, ddd, JHH = 7.4, 4.8, 1.1 Hz), 6.76 (2H, d, JHH = 8.6 Hz), 5.70–5.60 (1H, m), 4.99–4.92 (2H, m), 3.75 (1H, dd, JHH = 7.8, 5.9 Hz), 3.71 (3H, s), 3.54 (1H, d, JHH = 12.9 Hz), 3.43 (1H, d, JHH = 12.9 Hz), 2.50–2.43 (1H, m), 2.39–2.32 (1H, m). 13C (CDCl3, 125 MHz) δ: 163.3, 158.5, 149.4, 136.3, 135.3, 132.6, 129.3 (2C), 121.9 (2C), 117.5, 113.7 (2C), 62.8, 55.3, 51.1, 41.6. m/z [CI (+ve)] 269.1 [M + H]+, HRMS found [M + H]+ 269.1653, C17H21N2O requires 269.1654. IR (thin film) νmax = 2836, 1512, 1247, 905 cm−1.
1H (CDCl3, 400 MHz) δ: 7.36–7.32 (5H, m), 6.97 (2H, d, JHH = 8.6 Hz), 6.76 (2H, d, JHH = 8.3 Hz), 5.75–5.66 (1H, m), 5.35 (1H, br s), 5.26 (1H, br s), 5.08–4.99 (3H, m), 4.47 (1H, d, JHH = 15.7 Hz), 4.16 (1H, br s), 3.78 (3H, s), 2.74 (2H, br s). 19F (CDCl3, 470 MHz) δ: −102.4, −114.2. 13C (CDCl3, 125 MHz) δ: 163.3 (d, JCF = 30.0 Hz), 158.7, 158.2 (d, JCF = 271.3), 138.1, 134.2, 134.1 (2C), 129.2 (2C), 128.6 (2C) 128.1 (2C), 118.1, 113.6 (2C), 99.4 (d, JCF = 16.3 Hz), 55.2 (2C), 35.7, 33.5. m/z [EI (+ve)] 339.2 [M]+, HRMS found [M]+ 339.1639, C21H22FNO2 requires 339.1635. IR (thin film) νmax = 2937, 1637, 1512, 1417, 1246, 1176, 1033 cm−1.
1H (CDCl3, 400 MHz) δ: 7.27 (2H, d, JHH = 8.6 Hz), 6.98 (2H, d, JHH = 8.6 Hz), 6.89 (2H, d, JHH = 8.4 Hz), 6.77 (2H, d, JHH = 8.4 Hz), 5.74–5.64 (1H, m), 5.35 (1H, br s), 5.23 (1H, br s), 5.07–4.92 (3H, m), 4.46 (1H, d, JHH = 15.5 Hz), 4.14 (1H, br s), 3.83 (3H, s), 3.78 (3H, s), 2.69 (2H, br s). 19F (CDCl3, 470 MHz) δ: −102.1, −104.2. 13C (CDCl3, 125 MHz) δ: 163.2 (d, JCF = 30.0 Hz), 159.4, 159.3, 158.7, 158.5 (d, JCF = 271.3), 134.2, 134.1, 129.8 (2C), 129.2 (2C), 118.0, 113.9 (2C), 113.6 (2C), 99.2 (d, JCF = 15.0 Hz), 65.9, 55.3, 55.2, 36.04, 33.5. m/z [EI (+ve)] 369.2 [M]+, HRMS found [M]+ 369.1743, C22H24FNO3 requires 369.1740. IR (thin film) νmax = 2933, 2837, 1635, 1512, 1246, 1178, 1033 cm−1.
1H (CDCl3, 400 MHz) δ: 7.57 (2H, d, JHH = 8.0 Hz), 7.44 (2H, d, JHH = 8.0 Hz), 6.98 (2H, d, JHH = 8.4 Hz), 6.76 (2H, d, JHH = 8.4 Hz), 5.76–5.66 (1H, m), 5.41 (1H, d, JHH = 3.2 Hz), 5.29 (1H, d, JHH = 3.2 Hz), 5.14–5.09 (3H, m), 4.43 (1H, d, JHH = 15.6 Hz), 4.34 (1H, br. s), 3.80 (3H, s), 2.79 (2H, br. s). 19F (CDCl3, 377 MHz) δ: −62.3, −102.5, −104.4. 13C (CDCl3, 125 MHz) δ: 163.4 (d, JCF = 29.8 Hz), 159.0, 158.0 (d, JCF = 273.0 Hz), 142.5, 139.0, 137.8, 133.9, 129.9, 129.2 (2C), 128.8 (2C), 125.3 (2C), 125.0, 122.9, 118.5, 113.7 (2C), 99.8 (d, JCF = 12.5 Hz), 59.8, 55.2, 35.4. m/z [EI (+ve)] 407.1 [M]+, HRMS found [M]+ 407.1504, C22H21F4NO2 requires 407.1508. IR (thin film) νmax = 2939, 1639, 1514, 1415, 1325, 1246, 1120, 1068 cm−1.
1H (CDCl3, 400 MHz) δ: 8.07 (1H, d, JHH = 8.4 Hz), 7.87 (1H, br d, JHH = 8.4 Hz), 7.82 (1H, t, JHH = 4.6 Hz), 7.59–7.51 (2H, m), 7.44 (2H, d, JHH = 5.0 Hz), 6.76 (2H, d, JHH = 8.3 Hz), 6.63 (2H, d, JHH = 8.3 Hz), 6.57 (1H, br s), 5.87–5.76 (1H, m), 5.32 (1H, br d, JHF = 47.8 Hz), 5.14–5.05 (3H, m), 4.40 (1H, br d, JHH = 16.2 Hz), 3.91 (1H, dd, JHH = 16.2, 1.7 Hz), 3.75 (3H, s), 2.77 (2H, appt, JHH = 6.7 Hz). 19F (CDCl3, 377 MHz) δ: −103.7, −103.8. 13C (CDCl3, 100 MHz) δ: 162.9 (d, JCF = 30.4 Hz), 158.7, 158.2 (d, JCF = 263.3 Hz), 134.7, 133.9, 132.6, 132.5, 129.2, 128.8, 128.6 (2C), 126.9, 126.5, 124.7, 124.6, 123.4, 117.7, 114.4, 113.4 (2C), 99.9 (d, JCF = 15.8 Hz), 55.2 (2C), 54.1, 36.3. m/z [EI (+ve)] 389.2 [M]+. HRMS found [M]+ 389.1794, C25H24FNO2 requires 389.1791. IR (thin film) νmax = 2970, 1632, 1513, 1246, 1176 cm−1.
1H (CDCl3, 400 MHz) δ: 7.47 (2H, d, JHH = 8.1 Hz), 7.21 (2H, d, JHH = 8.1 Hz), 6.99 (2H, d, JHH = 8.6 Hz), 6.79 (2H, d, JHH = 8.6 Hz), 5.74–5.63 (1H, m), 5.40–5.25 (2H, m,), 5.19–5.05 (3H, m), 4.44 (1H, d, JHH = 16.0 Hz), 4.25 (1H, m), 3.81 (3H, s), 2.74–2.69 (2H, m). 19F (CDCl3, 470 MHz) δ: −102.3, −104.2. 13C (CDCl3, 125 MHz) δ: 163.3 (d, JCF = 29.4 Hz), 158.9, 157.9 (d, JCF = 273.3 Hz), 137.3, 133.9, 131.6 (2C), 130.3 (2C), 129.1 (2C), 129.0, 122.0, 118.3, 113. 7 (2C), 99.6 (d, JCF = 15.6 Hz), 55.3 (2C), 35.6, 23.9. m/z [EI (+ve)] 417.0 [M]+, HRMS found [M]+ 417.0739, C21H2179BrFNO2 requires 417.0740. IR (thin film) νmax = 2940, 1639, 1513, 1247, 1176 cm−1.
1H (CDCl3, 400 MHz) δ: 7.27 (2H, d, JHH = 8.0 Hz), 6.85 (2H, d, JHH = 7.2 Hz), 5.73–5.62 (1H, m), 5.26 (1H, br s), 5.15 (1H, br s), 5.13–5.02 (2H, m), 4.54–4.39 (2H, m), 4.19–4.01 (1H, m), 3.81 (3H, s), 2.33–2.19 (2H, m), 1.52–1.16 (3H, m), 0.85 (3H, d, JHH = 6.4 Hz,), 0.74 (3H, d, JHH = 6.0 Hz). 19F (CDCl3, 377 MHz) δ: −102.4 (dd, JFH = 47.5, 16.2 Hz), −103.6 (dd, JFH = 46.5, 15.1 Hz). 13C (CDCl3, 125 MHz) δ: 163.6 (d, JCF = 30.1 Hz), 158.7, 158.3 (d, JCF = 270.0 Hz), 135.4, 134.3, 130.3, 129.2 (2C), 118.0, 113.8 (2C), 98.5, 57.2, 55.3, 44.1, 42.0, 38.9, 24.6, 22.7. m/z [CI (+ve)] 320.2 [M + H]+, HRMS found [M + H]+ 320.2025, C19H27FNO2 requires 320.2026. IR (thin film) νmax = 2958, 1637, 1514, 1246 cm−1.
1H (CDCl3, 400 MHz) δ: 7.32 (2H, d, JHH = 8.6 Hz), 6.84 (2H, d, JHH = 8.6 Hz), 5.63–5.56 (1H, m), 5.27–4.91 (4H, m), 4.43 (2H, s), 3.81 (3H, s), 3.69 (1H, br t, JHH = 9.3 Hz), 2.51–2.44 (1H, m), 2.33–2.25 (1H, m), 1.85–1.51 (5H, m), 1.20–1.05 (2H, m), 0.97–0.81 (4H, m). 19F (CDCl3, 470 MHz) δ: −102.7. 13C (CDCl3, 125 MHz) δ: 164.6 (d, JCF = 30.0 Hz), 158.7, 158.2 (d, JCF = 270.0 Hz), 134.6, 130.1, 129.8 (2C), 117.7, 113.7 (2C), 98.5 (d, JCF = 15.0 Hz), 64.7, 55.3, 44.8, 40.9, 35.1, 30.5, 30.4, 26.3, 26.1, 26.0. m/z [CI (+ve)] 346.3 [M + H]+, HRMS found [M + H]+ 346.2176, C21H29FNO2 requires 346.2182. IR (thin film) νmax = 2924, 2852, 1635, 1513, 1442, 1246 cm−1.
1H (CDCl3, 400 MHz) δ: 7.36 (1H, br s), 7.00 (2H, d, JHH = 8.6 Hz), 6.77 (2H, d, JHH = 8.6 Hz), 6.35–6.25 (2H, m), 5.72–5.64 (1H, m), 5.38–5.24 (2H, m), 5.10–5.05 (3H, m), 4.55 (1H, d, JHH = 15.7 Hz), 4.27 (1H, m), 3.80 (3H, s), 2.65–2.59 (2H, m). 19F (CDCl3, 470 MHz) δ: −103.5, −105.3. 13C (CDCl3, 125 MHz) δ: 163.1 (d, JCF = 29.4 Hz), 158.6, 157.6 (d, JCF = 267.8 Hz), 151.9, 142.4, 133.1, 129.2 (2C), 118.7, 114.2, 113.6 (2C), 110.3, 109.2, 99.3, 57.7, 55.2, 44.4, 23.8. m/z [EI (+ve)] 329.2 [M]+, HRMS found [M]+ 329.1427, C19H20FNO3 requires 329.1428. IR (thin film) νmax = 2956, 1699, 1513, 1246, 1117 cm−1.
1H (CDCl3, 400 MHz) δ: 7.72 (2H, br s), 7.39 (1H, br s), 7.31 (2H, d, JHH = 8.3 Hz), 7.00 (2H, d, JHH = 8.6 Hz), 6.81 (2H, d, JHH = 8.6 Hz), 6.26–6.12 (2H, m), 5.75–5.65 (1H, m), 5.50–5.08 (3H, m), 4.81–4.53 (3H, m), 4.09 (1H, d, JHH = 6.0 Hz), 3.81 (3H, s), 2.49–2.41 (5H, m). 19F (CDCl3, 470 MHz) δ: −103.9. 13C (CDCl3, 125 MHz) δ: 162.4 (d, JCF = 29.4 Hz), 159.3, 157.9 (d, JCF = 276.8 Hz), 145.2, 143.4, 137.0, 135.9, 133.8, 130.0 (2C), 129.7 (2C), 129.3, 127.2 (2C), 117.8, 117.4, 114.0, 113.5 (2C), 98.9, 60.4, 55.2, 51.8, 46.7, 21.6. m/z [EI (+ve)] 482.1 [M]+, HRMS found [M]+ 482.1676, C26H27FN2O2S requires 482.1676. IR (thin film) νmax = 2975, 1652, 1511, 1247 cm−1.
1H (CDCl3, 400 MHz) δ: 8.55 (1H, s), 7.63 (1H, dt, JHH = 7.7, 1.8 Hz), 7.37 (1H, br s), 7.19 (1H, br s), 6.93 (2H, d, JHH = 8.6 Hz), 6.70 (2H, d, JHH = 8.6 Hz), 5.76–5.65 (1H, m), 5.47–5.02 (5H, m), 4.59 (2H, s), 3.76 (3H, s), 3.04–2.95 (1H, m), 2.89–2.80 (1H, m). 19F (CDCl3, 377 MHz) δ: −102.5, −105.1. 13C (CDCl3, 125 MHz) δ: 163.4 (d, JCF = 29.4 Hz), 158.5, 158.0 (d, JCF = 271.5 Hz), 157.7, 149.0, 136.6, 134.4, 129.7 (2C), 128.7, 124.1, 122.9, 118.3, 113.5 (2C), 99.5 (d, JCF = 16.5 Hz), 62.5, 59.5, 55.1, 35.0. m/z [CI (+ve)] 341.1 [M + H]+, HRMS found [M + H]+ 341.1669, C20H22FN2O2 requires 341.1665. IR (thin film) νmax = 1638, 1513, 1415, 1207, 1176 cm−1.
1H (CDCl3, 400 MHz) δ: 7.40–7.34 (3H, m), 7.19 (2H, d, JHH = 7.2 Hz), 7.15 (2H, d, JHH = 8.6 Hz), 6.86 (2H, d, JHH = 8.6 Hz), 5.77 (1H, m), 5.54 (1H, d, JHH = 14.8 Hz), 4.57 (1H, dd, JHH = 7.7, 2.6 Hz), 3.83 (3H, s), 3.51 (1H, d, JHH = 14.8 Hz), 2.99–2.93 (1H, m), 2.50–2.44 (1H, m). 19F (CDCl3, 470 MHz) δ: −126.8. 13C (CDCl3, 125 MHz) δ: 159.8 (d, JCF = 30.0 Hz), 159.2, 149.4 (d, JCF = 251.1 Hz), 139.4, 129.6 (2C), 129.0, 128.9 (2C), 128.0, 126.4 (2C), 114.1 (2C), 109.5 (d, JCF = 14.6 Hz), 57.0, 55.3, 47.2, 29.4 (d, JCF = 6.0 Hz). m/z [EI (+ve)] 311.2 [M]+. HRMS found [M]+ 311.1318, C19H18FNO2 requires 311.1322. IR (thin film) νmax = 2933, 2837, 1651, 1512, 1247, 1176, 1031 cm−1.
1H (CDCl3, 400 MHz) δ: 7.05 (2H, d, JHH = 8.8 Hz), 7.00 (2H, d, JHH = 8.8 Hz), 6.80 (2H, d, JHH = 8.8 Hz), 6.77 (2H, d, JHH = 8.8 Hz), 5.70–5.66 (1H, m), 5.66 (1H, d, JHH = 14.8 Hz), 4.41 (1H, dd, JHH = 7.6, 3.2 Hz), 3.74 (3H, s), 3.84 (3H, s), 3.39 (1H, d, JHH = 14.8 Hz), 2.84–2.79 (1H, m), 2.37–2.32 (1H, m). 19F (CDCl3, 470 MHz) δ: −126.7. 13C (CDCl3, 125 MHz) δ: 159.7 (d, JCF = 30.2 Hz), 159.4, 159.2, 149.4 (d, JCF = 252.5 Hz), 131.2, 129.6 (2C), 129.0, 127.6 (2C), 114.2 (2C), 114.1 (2C), 109.6 (d, JCF = 13.8 Hz), 56.6, 55.4, 55.3, 47.1, 29.6 (d, JCF = 5.0 Hz). m/z [EI (+ve)] 341.1 [M]+. HRMS found [M]+ 341.1420, C20H20FNO3 requires 341.1427. IR (thin film) νmax = 2951, 2837, 1651, 1512, 1462, 1247, 1178, 1033 cm−1.
1H (CDCl3, 400 MHz) δ: 7.64 (2H, d, JHH = 8.0 Hz), 7.30 (2H, d, JHH = 8.4 Hz), 7.14 (2H, d, JHH = 8.6 Hz), 6.85 (2H, d, JHH = 8.6 Hz), 5.78–5.75 (1H, m), 5.52 (1H, d, JHH = 14.8 Hz), 4.62 (1H, dd, JHH = 7.6, 2.0 Hz), 3.82 (3H, s), 3.53 (1H, d, JHH = 14.8 Hz), 3.05–2.98 (1H, m), 2.48–2.43 (1H, m). 19F (CDCl3, 470 MHz) δ: −62.3, −126.1. 13C (CDCl3, 125 MHz) δ: 159.6 (d, JCF = 30.1 Hz), 159.4, 149.4 (d, JCF = 253.8 Hz), 143.5, 130.6, 130.3, 129.6 (2C), 128.5, 126.8 (2C), 124.9 (2C), 114.2 (2C), 109.3 (d, JCF = 15.0 Hz), 56.7, 55.3, 47.5, 29.2 (d, JCF = 6.3 Hz). m/z [EI (+ve)] 379.0 [M]+, HRMS found [M]+ 379.1198, C20H17F4NO2 requires 379.1195. IR (thin film) νmax = 2970, 1737, 1654, 1512, 1413, 1327, 1249, 1112, 1068 cm−1.
1H (CDCl3, 400 MHz) δ: 7.97–7.94 (1H, m), 7.88 (1H, d, JHH = 8.2 Hz), 7.78–7.75 (1H, m), 7.56–7.53 (2H, m), 7.49 (1H, br t, JHH = 7.7 Hz), 7.34 (1H, d, JHH = 7.2 Hz), 7.15 (2H, d, JHH = 8.5 Hz), 6.86 (2H, d, JHH = 8.5 Hz), 5.74–7.69 (1H, m), 5.61 (1H, d, JHH = 14.8 Hz), 5.39 (1H, br d, JHH = 8.3 Hz), 3.83 (3H, s), 3.47 (1H, d, JHH = 14.8 Hz), 3.12–3.04 (1H, m), 2.70–2.62 (1H, m). 19F (CDCl3, 377 MHz) δ: −127.5. 13C (CDCl3, 125 MHz) δ: 160.5 (d, JCF = 31.2 Hz), 159.2, 149.1 (d, JCF = 255.0 Hz), 134.4, 133.5, 130.2, 129.7, 129.5 (2C), 129.1, 128.8, 126.7, 125.8, 125.3, 123.9 121.9, 114.1 (2C), 109.9 (d, JCF = 14.7 Hz), 55.3, 53.7, 47.4, 27.8 (d, JCF = 5.5 Hz). m/z [EI (+ve)] 361.2 [M]+. HRMS found [M]+ 361.1480, C23H20FNO2 requires 361.1478. IR (thin film) νmax = 2932, 1652, 1511, 1244, 1200 cm−1.
1H (CDCl3, 400 MHz) δ: 7.51 (2H, d, JHH = 8.5 Hz), 7.14 (2H, d, JHH = 8.6 Hz), 7.05 (2H, d, JHH = 8.5 Hz), 6.87 (2H, d, JHH = 8.6 Hz), 5.79–5.74 (1H, m), 5.50 (1H, d, JHH = 14.6 Hz), 4.52 (1H, dd, JHH = 7.6, 2.4 Hz), 3.83 (3H, s), 3.51 (1H, d, JHH = 14.6 Hz), 3.00–2.91 (1H, m), 2.46–2.38 (1H, m). 19F (CDCl3, 377 MHz) δ: −126.3. 13C (CDCl3, 100 MHz) δ: 159.6 (d, JCF = 31.0 Hz), 159.3, 149.3 (d, JCF = 253.0 Hz), 138.5, 132.1 (2C), 129.6 (2C) 128.6, 128.1 (2C), 122.0, 114.2 (2C), 109.4 (d, JCF = 15.0 Hz), 56.5, 55.3, 47.3, 29.3 (d, JCF = 6.0 Hz). m/z [CI (+ve)] 391.7 [M + H]+, HRMS found [M + H]+ 390.0489, C19H1879BrFNO2 requires 390.0505. IR (thin film) νmax = 2950, 1653, 1512, 1247, 1217 cm−1.
1H (CDCl3, 400 MHz) δ: 7.14 (2H, d, JHH = 8.4 Hz), 6.79 (2H, d, JHH = 8.8 Hz), 5.77–5.71 (1H, m), 5.27 (1H, d, JHH = 14.8 Hz), 3.73 (3H, s), 3.66 (1H, d, JHH = 14.8 Hz), 3.31–3.26 (1H, m), 2.48–2.44 (1H, m), 2.14–2.07 (1H, m), 1.72–1.65 (1H, m), 1.43–1.39 (1H, m), 1.27–1.17 (1H, m), 0.85 (3H, d, JHH = 6.8 Hz), 0.76 (3H, d, JHH = 6.8 Hz). 19F (CDCl3, 470 MHz) δ: −127.6. 13C (CDCl3, 125 MHz) δ: 159.2, 158.7 (d, JCF = 31.3 Hz), 149.6 (d, JCF = 252.5 Hz), 129.5, 129.4 (2C), 114.1 (2C), 109.8 (d, JCF = 13.8 Hz), 55.3, 52.1, 46.9, 39.6, 25.1, 24.6 (d, JCF = 5.0 Hz), 23.6, 21.5. m/z [EI (+ve)] 291.2 [M]+. HRMS found [M]+ 291.1629, C17H22FNO2 requires 291.1635. IR (thin film) νmax = 2955, 1651, 1512, 1249, 1201 cm−1.
1H (CDCl3, 400 MHz) δ: 7.23 (2H, d, JHH = 8.8 Hz), 6.87 (2H, d, JHH = 8.8 Hz), 5.83–5.79 (1H, m), 5.49 (1H, d, JHH = 14.9 Hz), 3.83 (3H, s), 3.79 (1H, d, JHH = 14.9 Hz), 3.18 (1H, br t, JHH = 6.8 Hz), 2.54–2.45 (1H, m), 2.36–2.28 (1H, m), 1.86–1.63 (6H, m), 1.29–1.07 (4H, m), 1.00–0.94 (1H, m). 19F (CDCl3, 470 MHz) δ: −128.2. 13C (CDCl3, 125 MHz) δ: 159.2, 159.0 (d, JCF = 31.1 Hz), 149.5 (d, JCF = 253.2 Hz, CF), 129.7, 129.3 (2C), 114.1 (2C), 110.6 (d, JCF = 14.2 Hz), 59.0, 55.3, 48.7, 40.8, 30.3, 30.2, 26.4, 26.3, 26.2, 22.8 (d, JCF = 5.5 Hz). m/z [CI (+ve)] 318.2 [M + H]+, HRMS found [M + H]+ 318.1871, C19H25FNO2 requires 318.1869. IR (thin film) νmax = 2925, 2850, 1645, 1511, 1247, 1198 cm−1.
1H (CDCl3, 400 MHz) δ: 7.40 (1H, dd, JHH = 1.7, 0.6 Hz), 7.22 (2H, d, JHH = 8.6 Hz), 6.90 (2H, d, JHH = 8.6 Hz), 6.36 (1H, dd, JHH = 3.2, 1.8 Hz), 6.19 (1H, br d, JHH = 3.2 Hz), 5.91–5.86 (1H, m), 5.48 (1H, d, JHH = 14.8 Hz), 4.59 (1H, dd, JHH = 7.0, 2.5 Hz), 3.84 (3H, s), 3.75 (1H, d, JHH = 14.8 Hz), 2.84–2.75 (1H, m), 2.67–2.59 (1H, m). 19F (CDCl3, 470 MHz) δ: −126.3. 13C (CDCl3, 125 MHz) δ: 159.4 (d, JCF = 30.0 Hz), 152.2, 149.1 (d, JCF = 252.5 Hz), 142.5, 131.0, 129.6 (2C), 128.9, 114.2 (2C), 110.3, 110.1 (d, JCF = 16.5 Hz), 107.5, 55.3, 51.6, 47.4, 26.2 (d, JCF = 5.9 Hz). m/z [EI (+ve)] 301.2 [M]+. HRMS found [M]+ 301.1111, C17H16FNO3 requires 301.1114. IR (thin film) νmax = 2957, 2364, 1654, 1513, 1415, 1248, 1117 cm−1.
1H (CDCl3, 400 MHz) δ: 7.50 (2H, d, JHH = 8.5 Hz), 7.37 (1H, dd, JHH = 1.7, 1.5 Hz), 7.30 (2H, d, JHH = 8.5 Hz), 6.89 (2H, d, JHH = 8.6 Hz), 6.83 (2H, d, JHH = 8.6 Hz), 6.28 (1H, t, JHH = 3.3 Hz), 6.16–6.15 (1H, m), 5.76–5.72 (1H, m), 5.30 (1H, d, JHH = 15.0 Hz), 4.95 (1H, d, JHH = 7.2 Hz), 3.85 (3H, s), 3.12 (1H, d, JHH = 15.0 Hz), 2.94–2.87 (1H, m), 2.71–2.65 (1H, m), 2.47 (3H, s). 19F (CDCl3, 377 MHz) δ: −127.9. 13C (CDCl3, 125 MHz) δ: 159.6 (d, JCF = 30.0 Hz), 159.1, 148.8 (d, JCF = 252.5 Hz), 145.4, 136.1, 132.5, 130.3 (2C), 128.9 (2C), 128.8, 126.4 (2C), 124.8, 114.8, 114.0 (2C), 112.0, 109.8 (d, JCF = 15.0 Hz), 55.3, 51.9, 47.4, 27.0 (d, JCF = 6.3 Hz), 21.7. m/z [ESI (+ve)] 477.1 [M + Na]+, HRMS found [M + Na]+ 477.1259, C24H23FN2O4SNa requires 477.1255. IR (thin film) νmax = 2955, 1630, 1515, 1447, 1276, 1205 cm−1.
1H (CDCl3, 400 MHz) δ: 7.45–7.37 (5H, m), 6.09 (1H, ddd, JHF = 11.1 Hz, JHH = 5.9, 3.3 Hz), 5.62 (1H, br s), 4.82 (1H, dd, JHH = 11.6, 5.8 Hz), 2.74–2.60 (2H, m). 19F (CDCl3, 470 MHz) δ: −129.9. 13C (CDCl3, 125 MHz) δ: 161.2 (d, JCF = 32.8 Hz), 149.1 (d, JCF = 253.2 Hz), 139.9, 129.2 (2C), 128.8, 126.4 (2C), 113.5 (d, JCF = 13.8 Hz), 56.1, 31.2 (d, JCF = 5.0 Hz). m/z [EI (+ve)] 191.1 [M]+, HRMS found [M]+ 191.0748, C11H10FNO requires 191.0746. IR (thin film) νmax = 2356, 1705, 1670, 1248 cm−1.
1H (CDCl3, 400 MHz) δ: 7.21 (2H, d, JHH = 8.6 Hz), 6.84 (2H, d, JHH = 8.6 Hz), 6.01–6.97 (1H, m), 5.57 (1H, br s), 4.67 (1H, dd, JHH = 12.1, 5.6 Hz,), 3.81 (3H, s), 2.60–2.46 (2H, m). 19F (CDCl3, 470 MHz) δ: −130.0. 13C (CDCl3, 125 MHz) δ: 161.1 (d, JCF = 31.3 Hz), 159.8, 149.8 (d, JCF = 253.8 Hz), 131.9, 127.6 (2C), 114.4 (2C), 113.6 (d, JCF = 13.8 Hz), 55.6, 55.4, 31.2 (d, JCF = 5.3 Hz). m/z [CI (+ve)] 222.1 [M + H]+, HRMS found [M + H]+ 222.0929, C12H13FNO2 requires 222.09230. IR (thin film) νmax = 1695, 1630, 1250 cm−1.
1H (CDCl3, 500 MHz) δ: 7.60 (2H, d, JHH = 8.2 Hz), 7.43 (2H, d, JHH = 8.2 Hz), 5.99 (1H, ddd, JHF = 11.8 Hz, JHH = 5.5, 3.6 Hz), 5.93 (1H, br s), 4.80 (1H, dd, JHH = 10.5, 6.1 Hz), 2.67–2.53 (2H, m). 19F (CDCl3, 470 MHz) δ: −62.4, −129.1. 13C (CDCl3, 125 MHz) δ: 161.1 (d, JCF = 31.3 Hz), 149.6 (d, JCF = 253.8 Hz), 144.0, 131.1, 130.9, 126.8 (2C), 126.1 (2C), 113.2 (d, JCF = 13.8 Hz), 55.4, 30.9 (d, JCF = 5.0 Hz). m/z [EI (+ve)] 259.1 [M]+, HRMS found [M]+ 259.0623, C12H9F4NO requires 259.0620. IR (thin film) νmax = 1720, 1705, 1680, 1305, 1180 cm−1.
1H (CDCl3, 400 MHz) δ: 7.96 (1H, d, JHH = 8.1 Hz), 7.85 (1H, br d, JHH = 7.9 Hz), 7.79 (1H, d, JHH = 8.1 Hz), 7.55–7.41 (4H, m), 6.04 (1H, dt, JHF = 11.0 Hz, JHH = 4.6 Hz), 5.74 (1H, br s), 5.56 (1H, t, JHH = 8.5 Hz), 2.81–2.76 (2H, m). 19F (CDCl3, 470 MHz) δ: −129.6. 13C (CDCl3, 125 MHz) δ: 161.2 (d, JCF = 33.0 Hz), 149.6 (d, JCF = 252.5 Hz), 135.3, 134.1, 130.0, 129.4, 129.2, 126.9, 126.2, 125.5, 123.9, 122.1, 113.7 (d, JCF = 12.5 Hz), 52.3, 29.7 (d, JCF = 5.0 Hz). m/z [EI (+ve)] 241.1 [M]+, HRMS found [M]+ 241.0902, C15H12FNO requires 241.0903. IR (thin film) νmax = 1715, 1797, 1320, 1180 cm−1.
1H (CDCl3, 400 MHz) δ: 7.56 (2H, d, JHH = 8.1 Hz), 7.27 (2H, d, JHH = 8.1 Hz), 6.09 (1H, dt, JHF = 10.9 Hz, JH = 4.7 Hz), 5.58 (1H, br s), 4.79 (1H, t, JHH = 8.5 Hz), 2.67–2.62 (2H, m). 19F (CDCl3, 470 MHz) δ: −129.6. 13C (CDCl3, 125 MHz) δ: 161.0 (d, JCF = 31.2 Hz), 149.6 (d, JCF = 253.2 Hz), 138.9, 132.3 (2C), 128.0 (2C), 122.7, 113.3 (d, JCF = 13.8 Hz), 55.5, 31.0 (d, JCF = 5.0 Hz). m/z [CI (+ve)] 269.8 [M + H]+, HRMS found [M + H]+ 269.9945, C11H1079BrFNO requires 269.9930. IR (thin film) νmax = 1705, 1685, 1205, 1010 cm−1.
1H (CDCl3, 500 MHz) δ: 6.07 (1H, ddd, JHF = 11.1 Hz, JHH = 5.9, 3.3 Hz), 5.59 (1H, br s, NH), 3.76–3.72 (1H, m), 2.49–2.40 (1H, m), 2.34–2.25 (1H, m), 1.74–1.63 (1H, m), 1.59–1.51 (1H, m), 1.45–1.36 (1H, m), 0.97 (3H, d, JHH = 6.6 Hz), 0.96 (3H, d, JHH = 6.6 Hz). 19F (CDCl3, 470 MHz) δ: −130.1. 13C (CDCl3, 100 MHz) δ: 161.2 (d, JCF = 28.0 Hz), 149.7 (d, JCF = 253.0 Hz), 113.7 (d, JCF = 13.0 Hz), 49.3, 44.0, 28.3 (d, JCF = 5.0 Hz), 24.4, 22.6, 22.2. m/z [CI (+ve)] 172.1 [M + H]+, HRMS found [M + H]+ 172.1144, C9H15FNO requires 172.1138. IR (thin film) νmax = 3219, 2934, 2906, 1696, 1669, 1264, 1206 cm−1.
1H (CDCl3, 400 MHz) δ: 5.98 (1H, dt, JHF = 11.4 Hz, JHH = 4.3 Hz), 5.54 (1H, br s), 3.35 (1H, br q, JHH = 7.7 Hz), 2.32–2.29 (2H, m), 1.74–1.61 (5H, m), 1.43–1.32 (1H, m), 1.19–0.97 (3H, m), 0.95–0.92 (2H, m). 19F (CDCl3, 470 MHz) δ: −130.5. 13C (CDCl3, 125 MHz) δ: 161.3 (d, JCF = 31.3 Hz), 149.6 (d, JCF = 252.5 Hz), 114.0 (d, JCF = 13.8 Hz), 56.0, 41.4, 28.8, 28.7, 26.1, 25.9 (d, JCF = 5.0 Hz), 24.9, 24.8. m/z [CI (+ve)] 198.1 [M + H]+, HRMS found [M + H]+ 198.1295, C11H17FNO requires 198.1294. IR (thin film) νmax = 2927, 2855, 1691, 1652, 1208, 1199 cm−1.
1H (CDCl3, 400 MHz) δ: 7.45–7.32 (5H, m), 5.93 (1H, br s), 4.95 (1H, dt, JHF = 46.27 Hz, JHH = 5.28 Hz), 4.61–4.60 (1H, m), 2.28–2.24 (1H, m), 2.17–2.03 (3H, m). 19F (CDCl3, 470 MHz) δ: −180.3. 13C (CDCl3, 125 MHz) δ: 167.5 (d, JCF = 20.1 Hz), 141.4, 129.0 (2C), 128.4, 126 1 (2C), 85.7 (d, JCF = 175.1 Hz), 57.3, 27.3 (d, JCF = 3.7 Hz), 26.2 (d, JCF = 20.0 Hz). m/z [EI (+ve)] 193.1 [M]+. HRMS found [M]+ 193.0904, C11H12FNO requires 193.0903. IR (thin film) νmax = 3194, 2066, 2958, 1666, 1329 cm−1.
1H (CDCl3, 400 MHz) δ: 7.25 (2H, d, JHH = 8.6 Hz), 6.94 (2H, d, JHH = 8.6 Hz), 5.83 (1H, s), 4.94 (1H, dt, JHF = 47.1 Hz, JHH = 4.6 Hz), 4.56–4.51 (1H, m), 3.84 (3H, s), 2.34–2.24 (1H, m), 2.13–1.96 (3H, m). 19F (CDCl3, 470 MHz) δ: −184.8. 13C (CDCl3, 125 MHz) δ: 167.2 (d, JCF = 22.1 Hz), 159.6, 133.4, 127.3 (2C), 114.4 (2C), 85.7 (d, JCF = 176.1 Hz), 57.0, 55.4, 27.4 (d, JCF = 4.6 Hz), 26.4 (d, JCF = 21.2 Hz). m/z [EI (+ve)] 223.1 [M]+. HRMS found [M]+ 223.0999, C12H14FNO2 requires 223.1009. IR (thin film) νmax = 2930, 1695, 1510, 1230 cm−1.
1H (CDCl3, 400 MHz) δ: 7.60 (2H, d, JHH = 8.2 Hz), 7.38 (2H, d, JHH = 8.2 Hz), 5.93 (1H, s), 4.86 (1H, dt, JHF = 47.1 Hz, JHH = 5.0 Hz), 4.59 (1H, br t, JHH = 5.7 Hz), 2.22–2.12 (1H, m), 2.11–1.89 (3H, m). 19F (CDCl3, 470 MHz) δ: −62.4, −185.0. 13C (CDCl3, 125 MHz) δ: 167.4 (d, JCF = 22.3 Hz), 145.4, 130.9, 130.6, 126.6 (2C), 126.1 (2C), 85.5 (d, JCF = 176.5 Hz), 57.0, 27.2 (d, JCF = 4.2 Hz), 26.1 (d, JCF = 21.0 Hz). m/z [EI (+ve)] 261.1 [M]+. HRMS found [M]+ 261.0773, C12H11F4NO requires 261.0777. IR (thin film) νmax = 3005, 2970, 1675, 1430 cm−1.
1H (CDCl3, 400 MHz) δ: 7.99–7.93 (2H, m), 7.87 (1H, d, JHH = 8.0 Hz), 7.62–7.51 (4H, m), 6.02 (1H, s), 5.48–5.46 (1H, m), 5.02 (1H, dt, JHF = 46.9 Hz, JHH = 5.7 Hz), 2.43–2.33 (1H, m), 2.28–2.23 (3H, m). 19F (CDCl3, 377 MHz) δ: −186.1. 13C (CDCl3, 100 MHz) δ: 168.3 (d, JCF = 19.9 Hz), 136.6, 134.0, 129.8, 129.4, 128.9, 126.8, 126.0, 125.4, 123.7, 121.9, 85.8 (d, JCF = 177.0 Hz), 53.3, 25.9 (d, JCF = 6.0 Hz), 25.7 (d, JCF = 20.0 Hz). m/z [CI (+ve)] 244.0 [M + H]+, HRMS found [M + H]+ 244.1137, C15H15FNO requires 244.1138. IR (thin film) νmax = 3240, 2900, 1650, 1110 cm−1.
1H (CDCl3, 400 MHz) δ: 6.00 (1H, s), 4.80 (1H, dt, JHF = 48.6 Hz, JHH = 4.5 Hz), 3.40–3.37 (1H, m), 2.16–2.13 (1H, m), 1.96–1.89 (1H, m), 1.81–1.77 (1H, m), 1.64–1.58 (2H, m), 1.40–1.31 (2H, m), 0.87 (3H, d, JHH = 6.6 Hz), 0.85 (3H, d, JHH = 6.6 Hz). 19F (CDCl3, 470 MHz) δ: −185.0. 13C (CDCl3, 125 MHz) δ: 167.4 (d, JCF = 20.0 Hz), 86.3 (d, JCF = 173.8 Hz), 50.8, 45.6, 26.5 (d, JCF = 21.3 Hz), 24.3, 24.0 (d, JCF = 3.7 Hz), 22.6, 22.3. m/z [CI (+ve)] 174.1 [M + H]+, HRMS found [M + H]+ 174.1300, C9H17FNO requires 174.1294. IR (thin film) νmax = 2950, 2935, 1630 cm−1.
1H (CDCl3, 500 MHz) δ: 5.93 (1H, s), 4.74 (1H, dt, JHF = 47.2 Hz, JHH = 4.4 Hz), 3.13–3.09 (1H, m), 2.21–2.13 (1H, m), 1.90–1.79 (1H, m), 1.74–1.62 (7H, m), 1.35–1.30 (1H, m), 1.22–1.14 (2H, m), 1.11–1.03 (1H, m), 0.99–0.89 (2H, m). 19F (CDCl3, 470 MHz) δ: −184.6. 13C (CDCl3, 125 MHz) δ: 167.4 (d, JCF = 19.9 Hz), 86.0 (d, JCF = 173.7 Hz), 57.8, 42.6, 28.6, 28.4, 26.9 (d, JCF = 21.3 Hz), 26.2, 26.0, 25.9, 20.2 (d, JCF = 3.4 Hz). m/z [EI (+ve)] 199.1 [M]+. HRMS found [M]+ 199.1376, C11H18FNO requires 199.1372. IR (thin film) νmax = 2926, 2870, 1664, 1410 cm−1.
1H NMR (CDCl3, 400 MHz) δ: 7.58 (2H, d, JHH = 8.0 Hz), 7.52 (2H, d, JHH = 8.0 Hz), 7.40–7.31 (5H, m), 6.02 (1H, ddd, JHH = 11.0, 5.8, 3.3 Hz), 5.59 (1H, s), 4.77 (1H, dd, JHH = 11.3, 6.0 Hz), 2.70–2.55 (2H, m). 19F (CDCl3, 377 MHz) δ: −129.8. 13C (CDCl3, 100 MHz) δ: 161.0 (d, JCF = 31.1 Hz), 149.9 (d, JCF = 253.6 Hz), 141.8, 140.2, 138.9, 128.9 (2C), 127.8 (2C), 127.7, 127.1 (2C), 126.8 (2C), 113.5 (d, JCF = 14.0 Hz), 55.8, 31.1 (d, JCF = 5.7 Hz). m/z [EI (+ve)] 267.1 [M]+, HRMS found [M]+ 267.1058, C17H14FNO requires 267.1059. IR (thin film) νmax = 2358, 1693, 1658, 1258, 1198 cm−1.
1H (CDCl3, 400 MHz) δ: 7.64 (2H, d, JHH = 7.5 Hz), 7.61 (2H, d, JHH = 7.5 Hz), 7.50–7.38 (5H, m), 5.91 (1H, s), 4.97 (1H, dt, JHF = 43.7 Hz, JHH = 4.5 Hz), 4.67–4.63 (1H, m), 2.36–2.27 (1H, m), 2.20–2.04 (3H, m). 19F (CDCl3, 377 MHz) δ: −185.1. 13C (CDCl3, 100 MHz) δ: 167.5 (d, JCF = 19.8 Hz), 141.4, 140.3, 140.2, 128.9 (2C), 127.7 (2C), 127.6, 127.1 (2C), 126.6 (2C), 85.7 (d, JCF = 176.0 Hz), 57.2, 27.3 (d, JCF = 4.0 Hz), 26.3 (d, JCF = 21.0 Hz). m/z [EI (+ve)] 269.0 [M]+, HRMS found [M]+ 269.1214, C17H16FNO requires 269.1216. IR (thin film) νmax = 3239, 2949, 2356, 1676, 1486 cm−1.
Footnotes |
† Electronic supplementary information (ESI) available: Full refinement details and crystallographic data (excluding structural factors). CCDC 1006297. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ob01547a |
‡ The author to whom crystallographic data questions should be addressed. |
§ Ian Sword Reader of Organic Chemistry. |
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