Synthesis of 6-(1,2,3-Triazoloalkyl)-α-Pyrones
by a Cascade RCM/CM and Click Chemistry Sequence

Fanny Cros; Jérémy Ruiz; Béatrice Pelotier; Olivier Piva

doi:10.1055/s-0030-1258577

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Synlett 2010(17): 2621-2624
DOI: 10.1055/s-0030-1258577

LETTER

Synthesis of 6-(1,2,3-Triazoloalkyl)-α-Pyrones by a Cascade RCM/CM and Click Chemistry Sequence

Fanny Cros, Jérémy Ruiz, Béatrice Pelotier, Olivier Piva*
Université de Lyon, Université Lyon 1, Institut de Chimie et de Biochimie Moléculaire et Supramoléculaire (ICBMS), UMR 5246 CNRS, Bat Raulin, 43 Bd du 11 novembre 1918, 69622 Villeurbanne cedex, France
Fax: +33(472)448136; e-Mail: piva@univ-lyon1.fr;

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Publication History

Received 19 July 2010
Publication Date:
23 September 2010 (online)

Abstract
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Abstract

A RCM/CM process followed by a further nucleophilic substitution allowed the formation of an azido pyrone which was implicated into a copper-catalyzed [3+2] cycloaddition with various alkynes. Among the different conditions tested, the use of copper(II) salts furnished the expected adducts in a range of 42-99% yield.

Key words

ring-closing metathesis - click chemistry - [3+2] cycloadditions - triazoles - tandem

References and Notes

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23

Tandem RCM/CM Process: A solution of ester 3 (250 mg, 1.5 mmol) and 4-bromobutene (0.45 mL, 4.3 mmol) in CH₂Cl₂ (150 mL) was deoxygenated by bubbling argon for 10 min. Grubbs’ II catalyst (2; 32 mg, 0.04 mmol) was added at once and the resulting solution was heated at 40 ˚C until complete disappearance of the starting material (TLC control). The solution was concentrated and purified by flash chromatography on silica leading to 4 as a colorless oil. Compound 4: ^¹H NMR (300 MHz, CDCl₃): δ = 2.48 (br t, J = 6.0 Hz, 2 H), 2.58 (br q, J = 6.0 Hz, 2 H), 3.03-3.05 (m, 2 H), 3.38 (t, J = 6.9 Hz, 2 H), 5.00-5.03 (m, 1 H), 5.33-5.60 (m, 2 H), 5.86 (br s, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 29.9, 32.2, 35.8, 38.5, 78.9, 121.8, 125.7, 126.3, 131.7, 168.8. IR: 701, 734, 972, 1073, 1226, 1267, 1380, 1738, 2923, 3034 cm^-¹. HRMS: m/z [M] calcd for C₁₀H₁₃O₂Br: 245.0177; found: 245.0177. Compound 5: ^¹H NMR (300 MHz, CDCl₃): δ = 2.29-2.38 (m, 2 H), 2.46-2.50 (m, 2 H), 3.03-3.05 (m, 2 H), 3.29 (t, J = 6.8 Hz, 2 H), 4.98-5.03 (m, 1 H), 5.55-5.60 (m, 2 H), 5.84-5.87 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 30.0, 32.2, 38.7, 50.8, 79.0, 122.0, 125.8, 126.4, 131.0, 168.8. IR: 701, 734, 972, 1073, 1226, 1267, 1380, 1738, 2923, 3034 cm^-¹. HRMS: m/z [M + H⁺] calcd for C₁₀H₁₄O₂N₃: 208.1086; found: 208.1085.

24

Compound 7a: ^¹H NMR (300 MHz, CDCl₃): δ = 2.37-2.63 (m, 2 H), 2.65-2.93 (m, 2 H), 2.93-2.95 (m, 2 H), 4.40-4.46 (m, 2 H), 4.89-4.92 (m, 1 H), 5.41-5.60 (m, 2 H), 5.67-5.79 (m, 2 H), 7.29-7.35 (m, 1 H), 7.39-7.44 (m, 2 H), 7.76 (s, 1 H), 7.79-7.83 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 29.7, 33.2, 38.3, 49.7, 78.5, 122.0, 121.8, 125.4, 127.1, 127.9, 128.6, 129.5, 130.5, 145.2, 147.2, 168.8. IR: 732, 911, 1049, 1076, 1226, 1382, 1736, 2925, 3136 cm^-¹. HRMS:
m/z [M + Na⁺] calcd for C₁₈H₁₉O₂N₃: 332.1375; found: 332.1375. Compound 7b: ^¹H NMR (300 MHz, CDCl₃): δ = 0.91 (t, J = 7.1 Hz, 3 H), 1.36 (sext, J = 7.1 Hz, 2 H), 1.63 (quint, J = 7.1 Hz, 2 H), 2.38-2.43 (m, 2 H), 2.56-2.62 (m, 2 H), 2.69 (t, J = 7.1 Hz, 2 H), 2.99-3.03 (m, 2 H), 4.33 (td, J = 6.8, 2.2 Hz, 2 H), 4.91-4.94 (m, 1 H), 5.40-5.56 (m, 2 H), 5.71-5.89 (m, 2 H), 7.28 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 13.8, 22.3, 25.3, 29.9, 31.6, 33.5, 38.6, 49.7, 78.8, 120.8, 122.0, 125.7, 127.1, 128.8, 130.0, 168.8. IR: 1049, 1225, 1379, 1735, 2930, 3042 cm^-¹. HRMS: m/z [M + H⁺] calcd for C₁₆H₂₄O₂N₃: 290.1869; found: 290.1869. Compound 7c: ^¹H NMR (300 MHz, CDCl₃): δ = 0.57 (td,
J = 7.0, 2.3 Hz, 3 H), 0.95 (br s, 12 H), 1.27 (t, J = 6.9 Hz, 2 H), 2.04-2.17 (m, 2 H), 2.28-2.39 (m, 2 H), 2.70 (d, J = 3.6 Hz, 2 H), 3.20 (t, J = 6.8 Hz, 2 H), 4.05-4.09 (m, 2 H), 4.29 (s, 2 H), 4.62-4.66 (m, 1 H), 5.11-5.28 (m, 2 H), 5.43-5.48 (m, 1 H), 5.52-5.58 (m, 1 H), 7.26 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 14.0, 22.5, 26.0, 29.1, 29.3, 29.4, 29.5, 29.8, 31.7, 33.3, 38.4, 49.6, 64.1, 70.7, 78.6, 121.9, 122.4, 125.6, 127.2, 129.7, 145.2, 168.7. IR: 703, 816, 973, 1049, 1097, 1223, 1378, 1462, 1739, 2855, 2926 cm^-¹. HRMS:
m/z [M + Na⁺] calcd for C₂₂H₃₅O₃N₃: 412.2571; found: 412.2564. Compound 7d: ^¹H NMR (300 MHz, CDCl₃): δ = 2.27-2.47 (m, 2 H), 2.70-2.59 (m, 2 H), 3.00 (m, 2 H), 3.91 (s, 3 H), 4.40-4.46 (m, 2 H), 4.87-4.97 (m, 1 H), 5.37-5.56 (m, 2 H), 5.68-5.73 (m, 1 H), 5.79-5.84 (m, 1 H), 8.08 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 29.9, 33.2, 38.4, 50.1, 52.1, 78.6, 122.1, 125.6, 127.6, 127.9, 129.1, 139.7, 161.1, 168.8. IR: 2952, 1735, 1543, 1435, 1370, 1228, 1161, 1046, 974, 809, 777, 701 cm^-¹. HRMS: m/z [M + Na⁺] calcd for C₁₄H₁₇O₄N₃: 314.1111; found: 314.1103. Compound 7e: ^¹H NMR (300 MHz, CDCl₃): δ = 0.29 (s, 9 H), 2.37-2.42 (m, 2 H), 2.57-2.70 (m, 2 H), 2.98-3.01 (m, 2 H), 4.36-4.44 (m, 2 H), 4.88-4.93 (m, 1 H), 5.46-5.56 (m, 2 H), 5.69-5.75 (m, 1 H), 5.79-5.86 (m, 1 H), 7.51 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = -1.0, 29.9, 33.6, 38.6, 49.3, 78.8, 121.9, 125.7, 127.1, 129.1, 129.9, 146.4, 168.8. IR: 701, 760, 843, 973, 1050, 1194, 1249, 1379, 1739, 2956 cm^-¹. HRMS: m/z [M + Na⁺] calcd for C₁₅H₂₃O₂N₃Si: 328.1452; found: 328.1442.

25

Compound 8a: ^¹H NMR (300 MHz, CDCl₃): δ = 2.12-2.18 (m, 2 H), 2.31-2.46 (m, 2 H), 2.65-2.71 (m, 2 H), 4.27-4.36 (m, 1 H), 4.46 (t, J = 6.7 Hz, 2 H), 5.43-5.62 (m, 2 H), 5.90 (dt, J = 9.7, 1.8 Hz, 1 H), 6.68 (dt, J = 9.7, 4.3 Hz, 1 H),7.30-7.35 (m, 1 H), 7.39-7.44 (m, 2 H), 7.77 (s, 1 H), 7.81-7.85 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 28.6, 33.5, 37.7, 50.0, 77.1, 121.2, 125.7, 128.2, 128.3, 128.9, 129.1, 129.2, 130.6, 145.1, 147.1, 164.3. IR: 731, 909, 1047, 1227, 1386, 1731, 2924, 3031 cm^-¹. HRMS: m/z [M + H⁺] calcd for C₁₈H₂₀O₂N₃: 310.1555; found: 310.1555. Compound 8b: ^¹H NMR (300 MHz, CDCl₃): δ = 0.92 (t, J = 7.0 Hz, 3 H), 1.37 (sext., J = 7.8 Hz, 2 H), 1.63 (quint, J = 7.8 Hz, 2 H), 2.19-2.23 (m, 2 H), 2.32-2.47 (m, 2 H), 2.57-2.63 (m, 2 H), 2.68 (t, J = 7.8 Hz, 2 H), 4.36 (t, J = 6.8 Hz, 2 H), 4.28-4.41 (m, 1 H), 5.46-5.50 (m, 2 H), 6.00 (dt, J = 9.8 Hz, 1.9 Hz, 1 H), 6.86 (dt, J = 9.8, 4.5 Hz, 1 H), 7.27 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 13.8, 22.2, 25.3, 28.5, 31.6, 33.4, 37.6, 49.6, 77.1, 120.6, 121.1, 127.7, 129.3, 145.2, 148.3, 164.2. IR: 2955, 2929, 2858, 1719, 1550, 1459, 1433, 1387, 1249, 1148, 1133, 1043, 972, 816, 666 cm^-¹. HRMS: m/z [M + H⁺] calcd for C₁₆H₂₄O₂N₃: 290.1863; found: 290.1862. Compound 8c: ^¹H NMR (300 MHz, CDCl₃): δ = 0.83 (t, J = 7.0 Hz, 3 H), 1.22 (br s, 12 H), 1.50-1.57 (m, 2 H), 2.13-2.29 (m, 2 H), 2.31-2.45 (m, 2 H), 2.56-2.67 (m, 2 H), 3.46 (t, J = 6.8 Hz, 2 H), 4.30-4.41 (m, 1 H), 4.36 (t, J = 6.9 Hz, 2 H), 4.55 (s, 2 H), 5.39-5.56 (m, 2 H), 5.96 (d, J = 9.6 Hz, 1 H), 6.81-6.87 (m, 1 H), 7.52 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 14.1, 22.7, 26.1, 28.6, 29.3, 29.5, 29.6, 29.7, 31.9, 33.4, 37.7, 49.9, 64.3, 71.0, 77.1, 121.2, 122.5, 128.0, 129.1, 145.2, 145.5, 164.3. IR: 666, 814, 971, 1044, 1097, 1245, 1382, 1429, 1459, 1720, 2851, 2926 cm^-¹. HRMS:
m/z [M + Na⁺] calcd for C₂₂H₃₅O₃N₃: 412.2571; found: 412.2566. Compound 8d: ^¹H NMR (300 MHz, CDCl₃): δ = 2.18-2.27 (m, 2 H), 2.29-2.46 (m, 2 H), 2.61-2.75 (m, 2 H), 3.92 (s, 3 H), 4.35 (q, J = 6.2 Hz, 1 H), 4.46 (t, J = 7.0 Hz, 2 H), 5.40-5.64 (m, 2 H), 5.99 (d, J = 9.9 Hz, 1 H), 6.81-6.87 (m, 1 H), 8.08 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 28.6, 33.3, 37.6, 50.2, 52.2, 77.0, 121.2, 127.6, 127.7, 128.6, 128.6, 145.2, 161.1, 164. 2. IR: 778, 815, 1044, 1207, 1231, 1248, 1366, 1387, 1435, 1543, 1720, 2917, 2950 cm^-¹. HRMS: m/z [M + Na⁺] calcd for C₁₄H₁₇O₄N₃: 314.1111; found: 314.1106. Compound 8e: ^¹H NMR (300 MHz, CDCl₃): δ = 0.28 (s, 9 H), 2.17-2.22 (m, 2 H), 2.25-2.47 (m, 2 H), 2.57-2.69 (m, 2 H), 4.30-4.43 (m, 1 H), 4.40 (t, J = 6.9 Hz, 2 H), 5.45-5.50 (m, 2 H), 5.97 (dt, J = 9.6, 1.7 Hz, 1 H), 6.81-6.87 (m, 1 H), 7.50 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = -1.0, 28.7, 33.6, 37.8, 49.3, 77.2, 121.3, 127.8, 127.9, 129.0, 129.3, 145.2, 146.6, 164.3. IR: 655, 759, 816, 843, 972, 1043, 1116, 1146, 1194, 1249, 1387, 1424, 1490, 1719, 2851, 2917, 2955 cm^-¹. HRMS: m/z [M + Na⁺] calcd for C₁₅H₂₃O₂N₃Si: 328.1452; found: 328.1440.