High Efficient of the Intermolecular Radical Reactions through three-Component Carbo-Oximation Process  using new ready available Sulfonyl oxime.

Introduction

Free radical multi component reactions (MCR) are more flexible and fulfill for an efficient carbo-functionalization of olefins¹. Radical MCRs have thus attracted a considerable attention. More recently, the addition of carbon fragments across the π-bond of non-activated olefins through free-radical pathways has received intense scrutiny, resulting in the description of useful transformations, such as for instance carbo-alkenylation^2,3, carbo-alkynylation⁴ and carbo-allylation of olefins. These processes also illustrate the importance of the influence of polar effects in free-radical MCRs⁵. Various electrophilic species may be envisioned, but sulfones including vinyl⁶-,alkynyl-, allyl⁷– and azido-sulfones⁸ hold a prominent place, due to the fast and efficient β-fragmentation of the sulfonyl moiety. Sulfones also allow to install other R³ substituents on the olefinic backbone such as (SPh, CN, N₃, Cl, etc..)⁹. Kim and co-workers¹⁰ have thus shown that sulfonyl oximes are also excellent radical acceptors¹¹, enabling the incorporation of an oxime onto a carbon framework as electrophilic radical traps. The strategy of the present work relies on the generalization of carbo-oximation of olefins as a formal carbo-formylation process. Carbo-formylation of an olefin under radical conditions has been described by Ryu et al. using carbon monoxide as the radical trap¹². The use of Kim’s sulfonyl oxime constitutes a more practical surrogate to toxic CO¹³, which generally requires relatively high pressure, and therefore specific autoclave equipment¹⁴.

Scheme 1  Click here to View scheme

 

Experimental

General: Equipment, Chemicals and Work Technique

All reactions were carried out under argon atmosphere with dry solvents under anhydrous conditions. Yields refer to chromatographically and spectroscopically (¹H NMR) homogeneous materials. Commercial reagents were used without purification. Benzene was distilled over sodium and benzophenone. DCE were distilled from CaH₂.¹H NMR and ¹³C  NMR were recorded on Bruker DPX-200 FT (¹H: 200 MHz, ¹³C: 50.3 MHz), Bruker Advance- 300FT (¹H: 300 MHz, ¹³C: 75.5 MHz),. All NMR spectra present in this work were measured in CDCl₃ solution. All chemical shifts are given in ppm. The chemical shifts (δ) and coupling constants (J) are expressed in ppm and Hz respectively. The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, b = broad. High resolution mass spectra were recorded on a Micromass ZABSpec TOF, on a Q-Tof Applied Biosystems and on Waters Q-Tof 2 apparatus. IR spectra were recorded on a Perkin-Elmer 1710 spectrophotometer or on a Perkin-Elmer aragon 1000 FT-IR spectrophotometer. Thin Layer Chromatography (TLC): Merck Kieselgel 60 F254 on aluminium foil from Macherey-Nagel. Detection was carried out under UV light at 254 nm and 365 nm. Column chromatography was performed with Merck Silica Gel 60 (70-230 mesh), (230-400 mesh ASTM) and Baker silica gel (0.063-0.200 mm) were used for flash chromatography.

General procedure for the three-component carbo-oximation with sulfonyl oxime (C) (Table 1). Three-component adducts (11-20).

In a dry two-neck round-bottom flask equipped with a condenser and a magnetic stirrer were successively added oxime  C (2 equiv, See Table 1), iodoester A (1 equiv) and the desired alkene partner B (4 equiv) in benzene (0.4 M). Argon was  bubbled directly into the flask for 30 min. (Bu₃Sn)₂ (1.5 equiv) was injected and the flask was heated to 60^oC. DTBHN was added after 5 min, then every 90 min if required (TLC). After total consumption of the starting iodide, the resulting mixture was concentrated in vacuo and purified by silica gel chromatography (Petroleum ether/ EtOAc) to afford the desired product.

tert-butyl-2-(cyano(methoxyimino)methyl)-3-(2-ethoxy-2-oxoethyl)piperidine-1-carboxylate (11)

Compound 11 was obtained according to the general procedure described above from ethyl iodoacetate A (53 mg, 0.25 mmol, 1 equiv), sulfonyl oxime C (119 mg, 0.5 mmol, 2 equiv), tert-butyl 3,4-dihydropyridine-1(2H)-carboxylate 1 (197 mg, 1 mmol, 4 equiv), (Bu₃Sn)₂ (0.19 mL,0.38 mmol), and DTBHN (4 mg, 0.04 mmol, 10 mol %) added by 5 mol % portion every 1.5 h, in degassed benzene (1.5 mL). Concentration in vacuo, followed by purification by flash chromatography (silica gel, 90/10 PE / EtOAc) afforded 11 (69 mg, 78%) as a colorless oil. R_f= 0.4 (PE/EtOAc 90/10). IR (ATR) ν_max (cm^-1) = 2957, 2855, 2711, 1732, 1690, 1513, 1278, 939.¹H NMR (CDCl₃, 300 MHz): δ (ppm) = 4.91 (d, 1H, J = 6 Hz, CH), 4.18 (q, 2H J = 3 and 6 Hz, CH₂), 4.02 (s, 3H, CH₃), 3.94-3.89 (m, 1H, CH), 3.39-3.34 (m, 1H, CH), 2.43-2.34 (m, 2H, CH₂), 2.18-2.11 (m, 2H, CH₂), 1.91-1.77 (m, 2H, CH₂), 1.45 (s, 9H, 3CH₃), 1.38 (appearant t, 3H, J = 6 and 3 Hz, CH₃), 1.25-1.19 (m, 1H, CH).¹³C NMR (CDCl₃, 75.5 MHz): δ (ppm) = 174.9 (C=O ester), 156.9 (C=O ester), 138.4 (C), 105.5 (CN), 81.0 (C),61.2 (C), 60.6 (C), 60.4 (C), 43.3 (C), 37.3 (C), 36.3 (C), 28.4 (C), 26.8 (C), 23.3 (C), 14.7 (C). HRMS (ESI): [M+H]⁺ C₁₇H₂₈N₃O₅ calcd. 354.1993, found 354.19330.

ethyl 2-(2-(cyano(methoxyimino)methyl)tetrahydro-2H-pyran-3-yl)acetate (12)

Compound 12 was obtained according to the general procedure described above from ethyl iodoacetate A (53 mg, 0.25 mmol, 1 equiv), sulfonyl oxime C (119 mg, 0.5 mmol, 2 equiv), 3,4-dihydro-2H-pyran 2 (84 mg, 1 mmol, 4 equiv), (Bu₃Sn)₂ (0.19 mL,0.38 mmol), and DTBHN (4 mg, 0.04 mmol, 10 mol %) added by 5 mol % portion every 1.5 h, in degassed benzene (1.5 mL). Concentration in vacuo, followed by purification by flash chromatography (silica gel, 88/12 PE / EtOAc) afforded 12 (64 mg, 81%) as a colorless oil. R_f= 0.4 (PE/EtOAc 88/12). IR (ATR) ν_max (cm^-1) = 2970, 1730, 1652, 1447, 1308, 1149, 1085, 688..¹H NMR (CDCl₃, 300 MHz): δ (ppm) = 5.17 (d, 1H, J = 6 Hz, CH), 4.17 (appearant q, 2H J = 3 and 6 Hz, CH₂), 3.99 (s, 3H, CH₃), 3.80-3.76 (m, 1H, CH), 3.71-3.67 (m, 1H, CH), 2.91-2.82 (m, 1H, CH), 2.30-2.26 (m, 1H, CH), 2.23-2.16 (m, 1H, CH), 2.06-2.01(m, 1H, CH), 1.38 (appearant t, 3H, J = 6 and 3 Hz, CH₃), 1.20-1.13 (m, 1H, CH).¹³C NMR (CDCl₃, 75.5 MHz): δ (ppm) = 174.9 (C=O ester), 132.1 (C), 110.8 (CN), 75.5 (C), 67.5 (C),61.2 (C), 60.6 (C), 60.4 (C), 36.8 (C), 34.8 (C), 25.9 (C), 24.7 (C), 14.7 (C). HRMS (ESI): [M+H]⁺ C₁₂H₁₉N₂O₄ calcd. 255.1345, found 252.1344.

ethyl 4-(cyano(methoxyimino)methyl)decanoate (13)

Compound 13 was obtained according to the general procedure described above from ethyl iodoacetate A (53 mg, 0.25 mmol, 1 equiv), sulfonyl oxime C (119 mg, 0.5 mmol, 2 equiv), oct-1-ene 3 (112 mg, 1 mmol, 4 equiv), (Bu₃Sn)₂ (0.19 mL,0.38 mmol), and DTBHN (4 mg, 0.04 mmol, 10 mol %) added by 5 mol % portion every 1.5 h, in degassed benzene (1.5 mL). Concentration in vacuo, followed by purification by flash chromatography (silica gel, 95/5 PE / EtOAc) afforded 13 (64 mg, 91%) as a colorless oil. R_f= 0.4 (PE/EtOAc 95/5). IR (ATR) ν_max (cm^-1) = 2976, 2957, 2855, 2711, 1732, 1690, 1513, 1278, 939.¹H NMR (CDCl₃, 300 MHz): δ (ppm) = 4.17 (q, 2H, J = 3 Hz, CH₂), 4.06-4.03 (m, 1H CH), 4.00 (s, 3H, CH₃), 2.30 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 2.00-1.96 (m, 1H, CH), 1.92-1.88 (m, 1H, CH), 1.57-1.55 (m, 2H, CH₂), 1.48-1.31 (m, 1H, CH and 5CH₂), 0.99 (appearant t, 3H, J = 6 and 3 Hz, CH₃).¹³C NMR (CDCl₃, 75.5 MHz): δ (ppm) = 174.3 (C=O ester), 135.3 (C), 114.9 (CN), 61.2 (C), 60.4 (C),34.2 (C), 32.9 (C), 32.6 (C), 31.6 (C), 29.9 (C), 29.3 (C), 27.8 (C), 22.9 (C), 14.7 (C), 14.0 (C). HRMS (ESI): [M+H]⁺ C₁₅H₂₇N₂O₇ calcd. 283.2021, found 283.2021.

ethyl 3-(1-(cyano(methoxyimino)methyl)cyclohexyl)propanoate (14)

Compound 14 was obtained according to the general procedure described above from ethyl iodoacetate A (53 mg, 0.25 mmol, 1 equiv), sulfonyl oxime C (119 mg, 0.5 mmol, 2 equiv), methylenecyclohexane 4 (96 mg, 1 mmol, 4 equiv), (Bu₃Sn)₂ (0.19 mL,0.38 mmol), and DTBHN (4 mg, 0.04 mmol, 10 mol %) added by 5 mol % portion every 1.5 h, in degassed benzene (1.5 mL). Concentration in vacuo, followed by purification by flash chromatography (silica gel, 94/6 PE / EtOAc) afforded 14 (59 mg, 89%) as a colorless oil. R_f= 0.36 (PE/EtOAc 94/6). IR (ATR) ν_max (cm^-1) = 1680, 1305, 1145, 1020, 987.¹H NMR (CDCl₃, 300 MHz): δ (ppm) = 4.17 (q, 2H, J = 3 Hz, CH₂), 4.00 (s, 3H CH₃), 2.29 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 1.91 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 1.87-1.82 (m, 2H, CH₂), 1.73-1.53 (m, 8H, 4CH₂), 1.37 (m, 2H, CH₂), 1.73-1.53 appearant t, 3H, J = 6 and 3 Hz, CH₃).¹³C NMR (CDCl₃, 75.5 MHz): δ (ppm) = 174.4 (C=O ester), 127.7 (C), 116.2 (CN), 61.2 (C), 60.4 (C),49.5 (C), 33.0 (C), 30.6 (C), 28.1 (C), 25.6 (C), 22.2 (C), 14.7 (C). HRMS (ESI): [M+H]⁺ C₁₄H₂₃N₂O₃ calcd. 267.1708, found 267.1709.

ethyl 3-(1-(cyano(methoxyimino)methyl)cyclopentyl)propanoate (15)

Compound 15 was obtained according to the general procedure described above from ethyl iodoacetate A (53 mg, 0.25 mmol, 1 equiv), sulfonyl oxime C (119 mg, 0.5 mmol, 2 equiv), methylenecyclopentane 5 (68 mg, 1 mmol, 4 equiv), (Bu₃Sn)₂ (0.19 mL,0.38 mmol), and DTBHN (4 mg, 0.04 mmol, 10 mol %) added by 5 mol % portion every 1.5 h, in degassed benzene (1.5 mL). Concentration in vacuo, followed by purification by flash chromatography (silica gel, 94/6 PE / EtOAc) afforded 15 (55 mg, 87%) as a colorless oil. R_f= 0.36 (PE/EtOAc 94/6). IR (ATR) ν_max (cm^-1) = 1690, 1304, 1140, 1015, 980.¹H NMR (CDCl₃, 300 MHz): δ (ppm) = 4.17 (appearant q, 2H, J = 3 and 6 Hz, CH₂), 3.99 (s, 3H CH₃), 2.36 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 2.34 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 1.91-1.80 (m, 2H, CH₂), 1.72-1.54 (m, 6H, 3CH₂), 1.38 (t, 3H, J = 3 Hz, CH₃).¹³C NMR (CDCl₃, 75.5 MHz): δ (ppm) = 174.4 (C=O ester), 127.6 (C), 116.5 (CN), 61.2 (C), 60.4 (C),59.9 (C), 36.1 (C), 30.6 (C), 30.2 (C), 23.6 (C), 14.7 (C). HRMS (ESI): [M+H]⁺ C₁₃H₂₁N₂O₃ calcd. 253.1552, found 253.1553.

ethyl 4-(cyano(methoxyimino)methyl)-4-ethylhexanoate (16)

Compound 16 was obtained according to the general procedure described above from ethyl iodoacetate A (53 mg, 0.25 mmol, 1 equiv), sulfonyl oxime C (119 mg, 0.5 mmol, 2 equiv), 3-methylenepentane 6 (84 mg, 1 mmol, 4 equiv), (Bu₃Sn)₂ (0.19 mL,0.38 mmol), and DTBHN (4 mg, 0.04 mmol, 10 mol %) added by 5 mol % portion every 1.5 h, in degassed benzene (1.5 mL). Concentration in vacuo, followed by purification by flash chromatography (silica gel, 94/6 PE / EtOAc) afforded 16 (59 mg, 92%) as a colorless oil. R_f= 0.35 (PE/EtOAc 94/6). IR (ATR) ν_max (cm^-1) = 1679, 1300, 1148, 1018, 980.¹H NMR (CDCl₃, 300 MHz): δ (ppm) = 4.43 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 4.22 (q, 2H, J = 3 Hz, CH₂), 4.02 (s, 3H, CH₃), 2.06 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 1.84 (appearant q, 2H, 2H, J = 3 and 6 Hz, CH₂), 1.58 (appearant q, 2H, J = 3 and 6 Hz, CH₂), 1.39 (t, 3H, J = 3 Hz, CH₃), 1.01 (t, 6H, J = 3 Hz, CH₃).¹³C NMR (CDCl₃, 75.5 MHz): δ (ppm) = 174.4 (C=O ester), 126.4 (C), 116.3 (CN), 61.2 (C), 60.4 (C),51.0 (C), 30.6 (C), 27.5 (C), 27.4 (C), 14.7 (C), 8.2 (C). HRMS (ESI): [M+H]⁺ C₁₃H₂₃N₂O₃ calcd. 255.1708, found 255.17080.

ethyl 5-cyano-5-(methoxyimino)-4-((trimethylsilyl)methyl)pentanoate (17)

Compound 17 was obtained according to the general procedure described above from ethyl iodoacetate A (53 mg, 0.25 mmol, 1 equiv), sulfonyl oxime C (119 mg, 0.5 mmol, 2 equiv), allyltrimethylsilane 7 (11.4 mg, 1 mmol, 4 equiv), (Bu₃Sn)₂ (0.19 mL,0.38 mmol), and DTBHN (4 mg, 0.04 mmol, 10 mol %) added by 5 mol % portion every 1.5 h, in degassed benzene (1.5 mL). Concentration in vacuo, followed by purification by flash chromatography (silica gel, 96/4 PE / EtOAc) afforded 17 (68 mg, 95%) as a colorless oil. R_f= 0.35 (PE/EtOAc 96/4). IR (ATR) ν_max (cm^-1) = 1700, 1670, 1150, 1201, 1015,  940.¹H NMR (CDCl₃, 300 MHz): δ (ppm) = 4.14 (q, 2H, J = 3 Hz, CH₂), 4.02 (s, 3H, CH₃), 3.53-3.48 (m, 1H, CH), 2.49 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 1.92-1.84 (m,  2H, 2H, CH₂), 1.37 (appearant t, 3H, J = 3 and 6 Hz, CH₃), 1.03-0.99 (m, 1H, CH), 0.74 (m, 1H, CH), 0.27 (s, 9H, 3CH₃).¹³C NMR (CDCl₃, 75.5 MHz): δ (ppm) = 174.3 (C=O ester), 130.1 (C), 114.9 (CN), 61.2 (C), 60.4 (C),37.2 (C), 32.6 (C), 30.2 (C), 14.7 (C), 14.1 (C). HRMS (ESI): [M+H]⁺ C₁₃H₂₅N₂O₃Si calcd. 285.1634, found 285.1634.

ethyl 5-cyano-4-ethoxy-5-(methoxyimino)pentanoate (18)

Compound 18 was obtained according to the general procedure described above from ethyl iodoacetate A (53 mg, 0.25 mmol, 1 equiv), sulfonyl oxime C (119 mg, 0.5 mmol, 2 equiv), ethoxyethene 8 (72 mg, 1 mmol, 4 equiv), (Bu₃Sn)₂ (0.19 mL,0.38 mmol), and DTBHN (4 mg, 0.04 mmol, 10 mol %) added by 5 mol % portion every 1.5 h, in degassed benzene (1.5 mL). Concentration in vacuo, followed by purification by flash chromatography (silica gel, 90/10 PE / EtOAc) afforded 18 (51 mg, 85%) as a colorless oil. R_f= 0.35 (PE/EtOAc 90/10). IR (ATR) ν_max (cm^-1) = 1700, 1680, 1630, 1307, 1144, 1070.¹H NMR (CDCl₃, 300 MHz): δ (ppm) = 4.85 (appearant t, 1H, J = 3 and 6  Hz, CH), 4.17 (q, 2H, J = 3 Hz, CH₂), 2.38 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 2.19-2.09 (m, 2H, CH₂), 1.38 (t, 3H, J = 3 Hz, CH₃), 1.20 (appearant t, 3H,  J = 3 and 6 Hz, CH₃).¹³C NMR (CDCl₃, 75.5 MHz): δ (ppm) = 174.3 (C=O ester), 135.4 (C), 109.5 (CN), 74.0 (C), 64.6 (C),61.2 (C), 60.4 (C), 31.0 (C), 30.6 (C), 15.5 (C), 14.7 (C). HRMS (ESI): [M+H]⁺ C₁₁H₁₉N₂O₄ calcd. 243.1345, found 243.1345.

3-(cyano(methoxyimino)methyl)-6-ethoxy-3-methyl-6-oxohexyl benzoate (19)

Compound 19 was obtained according to the general procedure described above from ethyl iodoacetate A (53 mg, 0.25 mmol, 1 equiv), sulfonyl oxime C (119 mg, 0.5 mmol, 2 equiv), 3-methylbut-3-en-1-yl benzoate 9 (72 mg, 1 mmol, 4 equiv), (Bu₃Sn)₂ (0.19 mL,0.38 mmol), and DTBHN (4 mg, 0.04 mmol, 10 mol %) added by 5 mol % portion every 1.5 h, in degassed benzene (1.5 mL). Concentration in vacuo, followed by purification by flash chromatography (silica gel, 92/8 PE / EtOAc) afforded 19 (71 mg, 79%) as a colorless oil. R_f= 0.37 (PE/EtOAc 92/8). IR (ATR) ν_max (cm^-1) = 2955, 1750, 1733, 1446, 1430, 1300, 1280, 1080, 750.¹H NMR (CDCl₃, 300 MHz): δ (ppm) = 7.94 (d, 2H, CH_ar), 7.48-7.37 (m, 3H,  CH_ar), 4.24 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 4.16 (q, 2H, J = 3 Hz, CH₂), 3.99 (s, 3H, CH₃), 2.31 (t, 2H,  J = 6 Hz, CH₂), 2.13-2.04 (m, 4H, 2CH₂), 1.32 (s, 3H, CH₃).¹³C NMR (CDCl₃, 75.5 MHz): δ (ppm) = 174.4 (C=O ester), 167.0 (C=O ester), 133.0 (C), 130.2 (C_ar), 129.6 (C_ar), 128.8 (C_ar), 113.2 (CN), 64.4 (C), 61.2 (C),60.4 (C), 38.7 (C), 36.8 (C), 30.5 (C), 29.7 (C), 25.0 (C), 14.7 (C). HRMS (ESI): [M+H]⁺ C₁₉H₂₅N₂O₅ calcd. 361.1763, found 361.17630.

ethyl 4-(cyano(methoxyimino)methyl)-6-hydroxy-4-methylhexanoate (20)

Compound 20 was obtained according to the general procedure described above from ethyl iodoacetate A (53 mg, 0.25 mmol, 1 equiv), sulfonyl oxime C (119 mg, 0.5 mmol, 2 equiv), 3-methylbut-3-en-1-ol 10 (86 mg, 1 mmol, 4 equiv), (Bu₃Sn)₂ (0.19 mL,0.38 mmol), and DTBHN (4 mg, 0.04 mmol, 10 mol %) added by 5 mol % portion every 1.5 h, in degassed benzene (1.5 mL). Concentration in vacuo, followed by purification by flash chromatography (silica gel, 94/6 PE / EtOAc) afforded 20 (47 mg, 76%) as a colorless oil. R_f= 0.34 (PE/EtOAc 90/10). IR (ATR) ν_max (cm^-1) = 2920, 1730, 1650, 1315, 1201, 1105, 939.¹H NMR (CDCl₃, 300 MHz): δ (ppm) = 4.16 (appearant q, 2H, J = 3 and 6 Hz, CH₂), 4.01 (s, 3H, CH₃), 3.49 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 2.31 (appearant t, 2H,  J = 3 and 6 Hz, CH₂), 2.01 (t, 2H, J = 6 Hz, CH₂), 1.85 (appearant t, 2H, J = 3 and 6 Hz, CH₂), 1.37 (t, 3H, J = 3 Hz, CH₃), 1.31 (s, 3H, CH₃), 0.56 (s, 1H, OH).¹³C NMR (CDCl₃, 75.5 MHz): δ (ppm) = 174.4 (C=O ester), 128.8 (C), 113.2 (CN), 61.2 (C), 60.4 (C),59.9 (C), 38.7 (C), 38.0 (C), 30.5 (C), 29.7 (C), 25.0 (C), 14.7 (C). HRMS (ESI): [M+H]⁺ C₁₂H₂₁N₂O₄ calcd. 257.1501, found 257.1501.

Results and Disussion

The 3-component carbo-oximation process was first carried out using new sulfonyl oxime, ready available from the corresponding α-sulfonyl nitrile¹⁵. Such reactions proceed through the preliminary decomposition of DTBHN initiator to produce nitrogen gas and ^tBuO radical.  Addition of the latter onto tin compound produced tin radical. Tin radical can then abstract the iodide group from ethyliodoacetate (A) and form the electrophilic radical (Ai). Addition of an electron-poor radical to the less hindered end of an olefin (B), forming a new nucleophilic radical (Bi), which can then be trapped by an electrophilic partner such as cyanosulfonyl oxime (C), affording the expected products (P) and expel the tosylate group through β-fragmentation process to propagate the radical chain Scheme 2.

Scheme 2  Click here to View scheme

 

The 3-component carbo-oximation process was first carried out using cyano sulfonyl oxime B (2 eq.), an excess of the olefins 1-10 (4 eq.), ethyliodoester as precursor A (1 eq.), and (Bu₃Sn)₂ (1.5 equiv) in benzene (degassed) as a solvent. The reaction was initiated using di-tert-butylhyponitrite (DTBHN) (10 mol %). The results are summarized in Scheme 3 (Table 1) below. Generally good and reproducible yields of the 3-component adducts 11-20 were obtained (76-95%). The final oximes were easily isolated through chromatography over silica gel. A broad variety of substituents on the olefin is compatible with the reaction conditions. The reaction conditions were found to be compatible with  Boc-protected amines and dihydro-pyran as an electron-rich olefins (entry 1 and 2). The iodoester substrate A was also shown to react efficiently with normal olefin and methylene cyclohexene as well as methylene cyclopentene (entry 3-6). The reaction was extended with using electron-rich olefins such as allylsilanes and vinylether, which produced the expected products 17 and 18 in very good yields (entry 7 and 8). Generation of products 19 and 20 with quaternary center carbon was also obtained with a good yield (entry 9 and 10).

Scheme 3 Click here to View scheme

 

Table 1: Three-component Carbo-oximation of various Olefins using sulfonyl oxime nitrile.   Click here to View table

 

Conclusion

In summary, a sequential carbo-oximation protocol involving a three-component radical process was developed under mild conditions in a single pot starting from readily available ehtyliodoacetate, different olefins and new sulfonyl oxime acceptor. This three-component reaction proceed through the addition of a radical species derived from a iodoester and a vinylsulfone across the olefinic groups backbone and formation of two new carbon-carbon bonds,

which enables facile hydrolysis of the oxime under mild conditions after post-functionalization of the carbo-oximation products and provides a rapid access to lactones, after Mukaiyama aldol or Sakurai allylation reactions or more complex piperidinones using Pictete-Spengler processes.

Acknowledgements

We gratefully acknowledge (Bordeaux 1) University (France), the Kurdistan Government and the HCDP Program for financial support.

 References

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