furan ring Cascade reaction for the construction of CF3 ... fileS1 Cascade reaction for the construction of CF3 containing tetrasubstituted furan ring Manoj K. Choudhary,a,b Venkata

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Cascade reaction for the construction of CF3 containing tetrasubstituted furan ringManoj K. Choudhary,a,b Venkata Subba Rao Ganga,a,b Tushar Menapara,a,b Rukhsana I. Kureshy,*a,b

Noor-ul H. Khan,a,b Sayed H. R. Abdi,a,b Eringathodi Suresh,b,c

a Inorganic Materials and Catalysis Division, Central Salt and Marine Chemicals Research Institute (CSMCRI),

Bhavnagar- 364 002, Gujarat, India. Phone Number: +91-0278-2567760/2568923; Fax: +91-0278-2566970;

E-mail: [email protected] bAcademy of Scientific and Innovative Research (AcSIR), Central Salt and Marine Chemicals Research Institute

(CSMCRI), Council of Scientific & Industrial Research (CSIR), G. B. Marg, Bhavnagar- 364 002, Gujarat,

India.cAnalytical Chemistry Discipline, Central Salt and Marine Chemicals Research Institute (CSMCRI),

Bhavnagar- 364 002, Gujarat, India.

List of Contents:

1. General information S2

2. Synthesis and characterization of activated nitroolefin 2a&2b S2

3. Typical experimental procedure S2

4. Characterization data of products S2-S34

4.1 Characterization data of TFMK products with 2a S2-S4

4.2 Characterization data of TFMK products with 2b S4-S6

4.3 Characterization data of TFMK products with 2c S6-S7

4.4 1H and 13C-NMR spectra of TFMK products with 2a S7-S21

4.5 1H and 13C-NMR spectra of TFMK products with 2b S22-S31

4.6 1H and 13C-NMR spectra of TFMK products with 2c S32-S35

5. References S35

Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2016

mailto:[email protected]

S2

1. General Information

Trifluromethylketones (TFMK), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were purchased from Sigma-

Aldrich chemicals and used without further purification. Melting points were recorded using FP62 Mettler

Toledo. FTIR spectra were recorded on a Perkin Elmer Spectrum GX spectrophotometer as KBr pellet. Mass

analyses (HRMS) were performed using positive electron spray ionization (ESI+) technique on a waters Q TOF-

micro mass spectrometer for all these complexes upon dissolving in CH3CN solvent. 1H and 13C NMR spectra

were recorded on a Bruker Avance II 500 MHz FT-NMR spectrometer. Chemical shifts for proton resonances

are reported in ppm () relative to tetramethyl silane (TMS) and coupling constants (J) were given in Hertz

(Hz). For the product purification flash chromatography was performed using silica gel 230-400 mesh. The

following abbreviations were used to designate chemical shift multiplicities: s = singlet, d = doublet, t = triplet,

m =multiplet, br = broad, q = Quintet, coupling constants are given in Hertz (Hz).

2. Synthesis and characterization of activated nitroolefin

Activated nitroolefin (2a, 2b and 2c) was prepared and characterization according to the method reported in the

literature.1

3. Typical experimental procedure

Trifluromethylketones (1a-j) and (1a׳-i׳ ) (0.5 mmol, 1.0 eq.) and activated nitroolefin (2a, 2b and 2c) (0.6

mmol, 1.2 eq.) were taken in 0.8 mL of dry CH3CN in a sample vial with a magnetic stirring bar. To the

resulting solution, DBU (20 mol%) as Lewis base was added into the reaction and allowed to stir at 40 °C. After

running the reaction for the specified time, the volatile components were removed under reduced pressure, and

the crude product was purified by column chromatography (Hexane/AcOEt: 90/10).

4. Characterization data of trifluoromethyl ketone (TFMK) products:

4.1. Characterization data of trifluoromethyl ketone (TFMK) products with 2a:

(i). (Z)-5-(4-fluorophenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3a);

The title compound was isolated by column chromatography (hexane/AcOEt: 90/10) as a White solid; Yield:

95%; Melting point: 152-153.0 °C; FTIR (KBr): νmax = 3402, 2363, 1681, 1239, 1193, 1033, 985, 763 cm-1; 1H

NMR (500MHz, CDCl3, ppm): = 7.73–7.72 (m, 2H), 7.64–7.62 (m, 2H), 7.42-7.40 (m, 3H),7.15-7.14 (m,

2H), 7.04 (s, 1H, =CH-); 13C NMR (125 MHz, CDCl3, ppm): δ = 164.40, 162.41, 157.58, 137.41, 130.34 (d,

JC-F = 125 Hz, -CF3), 128.70, 128.56, 128.06, 123.96, 121.70, 116.00 (d, J = 85 Hz), 90.62-90.10 (q, JC-F = 260

S3

Hz); 19F NMR (400 MHz, CDCl3) δ = -77.55 (s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for

C17H12F4NO2: 338.0804, found 338.0807.

(ii). (Z)-5-(3-fluorophenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3b);


92%; Melting point: 127-128 °C; FTIR (KBr): νmax = 3403, 2363, 1680, 1248, 1176, 1035, 984, 763 cm-1; 1H

NMR (500MHz, CDCl3, ppm): = 7.73–7.68 (m, 2H), 7.62 (m, 1H), 7.42-7.39 (m, 5H), 7.13-7.10 (m, 1H),

7.00 (s, 1H, =CH-).; 13C NMR (125 MHz, CDCl3, ppm): δ = 160.48, 155.55, 152.70, 132.79, 130.41-130.26

(d, JC-F = 75 Hz, -CF3), 125.85 (d, J = 80 Hz), 125.39, 123.96, 123.31, 117.00, 115.16, 112.23 (d, J = 210 Hz),

109.47 (d, J = 240 Hz), 86.33, 85.66-84.39 (q, JC-F = 650 Hz); 19F NMR (400 MHz, CDCl3) δ = -77.30 (s, 3F), -

111.00-111.04 (m) ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for C17H12F4NO2: 338.0804, found 338.0803.

(iii). (Z)-5-(3,4-difluorophenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3c);


91%; Melting point: 133-135 °C; FTIR (KBr): νmax = 3443, 2363, 1676, 1523, 1290, 1179, 1037, 983, 768, 731

cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.77–7.72 (m, 2H), 7.54-7.39 (m, 5H), 7.33-7.20 (m, 1H), 7.01 (s,

1H, =CH-); 13C NMR (125 MHz, CDCl3, ppm): δ = 157.27, 153.78, 153.78-152.73 (dd, JC-F = 380 Hz),

148.73-147.72 (dd, JC-F = 360 Hz), 137.74, 130.20, 129.77 (d, JC-F = 80 Hz, -CF3), 128.72, 128.43, 128.06,

125.47, 122.96, 117.66, 116.30, 90.62-88.68 (q, JC-F = 645 Hz); 19F NMR (400 MHz, CDCl3) δ = -76.87 (s, 3F),

-135.34-135.39 (m) ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for C17H11F5NO2: 356.0710, found 356.0698.

(iv). (Z)-3-phenyl-5-(trifluoromethyl)-5-(3-(trifluoromethyl) phenyl)furan-2(5H)-one oxime (3d);


90%; Melting point: 99-101 °C; FTIR (KBr): νmax = 3403, 2362, 1683, 1334, 1192, 1038, 984, 763, 684 cm-1; 1H

NMR (500MHz, CDCl3, ppm): = 8.26 (brs, 1H), 7.92–7.89 (m, 2H), 7.72-7.69 (m, 3H), 7.59-7.57 (m, 1H),

7.40-7.57 (m, 3H), 7.07 (s, 1H, =CH-); 13C NMR (125 MHz, CDCl3, ppm): δ= 157.36, 138.03, 134.02,

131.78-131.00 (q, JC-F = 360 Hz), 130.25, 130.03-129.54 (q, JC-F = 245 Hz, -CF3), 128.78, 128.48, 128.09,

126.63, 124.79, 123.88, 123.40, 122.62, 121.61, 90.58-90.07 (q, JC-F = 255 Hz); 19F NMR (400 MHz, CDCl3) δ

= -77.46 (s, 3F), -62.64 (s) ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for C18H12F6NO2: 388.0772, found

388.0757.

(v). (Z)-5-(4-chlorophenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3e);


93%; Melting point: 145-146 °C; FTIR (KBr): νmax = 3405, 2363, 1678, 1274, 1194, 1035, 985, 762, 685 cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.71–7.70 (m, 2H), 7.59–7.57 (m, 2H), 7.42-7.40 (m, 5H), 7.01 (s, 1H,

=CH-); 13C NMR (125 MHz, CDCl3, ppm): δ = 157.49, 137.50, 135.98, 131.36, 130.12, 129.09, 128.70,

128.60, 128.06, 127.92, 123.89, 121.63, 90.53-90.07 (q, JC-F = 230 Hz); 19F NMR (400 MHz, CDCl3) δ = -77.45

(s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for C17H12ClF3NO2: 354.0509, found 354.0521.

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(vi). (Z)-3-phenyl-5-(thiophen-2-yl)-5-(trifluoromethyl)furan-2(5H)-one oxime (3f);


90%; Melting point: 122-123 °C; FTIR (KBr): νmax = 3403, 2363, 1687, 1274, 1178, 1039, 982, 768, 684 cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.72-7.69 (m, 2H), 7.42-7.34 (m, 5H), 7.09-7.04 (m, 1H), 6.94 (s, 1H,

=CH-); 13C NMR (125 MHz, CDCl3, ppm): δ = 157.42, 137.66, 134.48, 130.34, 130.17, 128.75, 128.58,

128.13, 127.72, 127.45, 125.43, 119.78, 89.91, 89.91-87.57 (q, JC-F = 675 Hz); 19F NMR (400 MHz, CDCl3) δ =

-77.42 (s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for C15H11F3NO2S: 326.0463, found 326.0474.

(vii). (Z)-3,5-diphenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3g);

The title compound was isolated by column chromatography (hexane/AcOEt: 90/10) as a White solid;

Yield:75%; Melting point: 118-120 °C; FTIR (KBr): νmax = 3408, 2363, 1681, 1274, 1172, 1026, 945, 762, 683

cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.64–7.63 (m, 2 H), 7.57–7.56 (m, 2H), 7.37-7.330 (m, 6H), 6.99

(s, 1H, =CH-); 13C NMR (125 MHz, CDCl3, ppm): δ= 157.82, 137.20, 132.87, 130.82, 130.06, 129.74, 128.89,

128.74 (d, JC-F = 75 Hz, -CF3), 128.12, 126.53, 124.13, 121.86, 91.09-90.32 (q, JC-F = 260 Hz); 19F NMR (400

MHz, CDCl3) δ = -77.32 (s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for C17H13F3NO2: 320.0898 found

320.0892.

(viii). (Z)-5-(4-methoxyphenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3h);




(s, 1H, =CH-), 6.97-6.95 (d, J= 10 Hz, 2H), 3.82 (s, 3H, -OCH3); 13C NMR (125 MHz, CDCl3, ppm): δ =

160.54, 157.88, 136.94, 130.82, 129.91, 128.87, 128.62, 128.07, 127.94, 124.82, 114.20, 90.85-90.35 (q, JC-F =

250 Hz), 85.36; 19F NMR (400 MHz, CDCl3) δ = -77.58 (s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for

C18H15F3NO3: 350.1004, found 350.0999.

(ix). (Z)-5-(2,4-dimethoxyphenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3i);




(s, 1H, =CH-), 3.90 (s, 3H, -OCH3), 3.84 (s, 3H, -OCH3); 13C NMR (125 MHz, CDCl3, ppm): δ = 162.06,

157.81, 135.70, 132.22, 129.93, 129.55-129.40 (d, JC-F = 75 Hz, -CF3), 128.52, 128.06, 125.96, 120.27, 113.61,

104.92, 99.46, 90.50-89.18 (q, JC-F = 650 Hz), 55.75, 55.45; 19F NMR (400 MHz, CDCl3) δ = -77.73 (s, 3F)

ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for C19H17F3NO4: 380.1110, found 380.1124.

(x). (Z)-5-(4-methylphenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3j);



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cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.72–7.71 (m, 2 H), 7.53–7.51 (m, 2H), 7.40-7.39 (m, 3H), 7.26-

7.24 (m, 2H), 7.06 (s, 1H, =CH-), 2.37 (s, 3H, -CH3); 13C NMR (125 MHz, CDCl3, ppm): δ= 157.87, 139.77,

136.94, 130.85, 129.90, 129.49, 128.86, 128.61, 128.07, 126.37, 124.12, 121.86, 90.02-90.49 (q, JC-F = 240 Hz),

21.15; 19F NMR (400 MHz, CDCl3) δ = -77.44 (s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for

C18H15F3NO2: 334.1055, found 334.1061.

4.2. Characterization data of trifluoromethyl ketone (TFMK) products with 2b:

(i). (Z)-3-(4-chlorophenyl)-5-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (4a);

The title compound was isolated by column chromatography (hexane/AcOEt: 90/10) as a White solid; Yield: 86

%; Melting point: 149-150 °C; FTIR (KBr): νmax = 3340, 2363, 1683, 1274, 1177, 1094, 955, 823, 758 cm-1; 1H

NMR (500MHz, CDCl3, ppm): = 7.70–7.68 (d, 2H, J = 10 Hz), 7.64–7.63 (m, 2H), 7.64-7.44 (m, 3H), 7.38-

7.36 (m, 2H), 7.18 (s, 1H), 7.08 (s, 1H, =CH-); 13C NMR (125 MHz, CDCl3, ppm): δ = 157.53, 136.12,

135.97, 132.65, 130.95, 129.81, 129.44, 128.92, 127.19, 126.45, 124.02, 121.76, 116.20, 91.08-90.56 (q, JC-F =

260 Hz); 19F NMR (400 MHz, CDCl3) δ = -77.35 (s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+Na]+ calcd for

C17H11ClF3NO2Na: 376.0328, found 376.0337.

(ii). (Z)-3-(4-chlorophenyl)-5-(3,4-difluorophenyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4b);



cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.77 (s, 1H), 7 (s, 1H), 7.52-7.48 (m, 1H), 7.40-7.36 (m, 3H),

7.28-7.23 (m, 1H), 7.09 (s, 1H), 7.00 (s, 1H, =CH-); 13C NMR (125 MHz, CDCl3, ppm): δ = 157.01, 152.26-

151.50 (dd, JC-F = 380 Hz), 150.24-149.49 (dd, JC-F = 375 Hz), 136.55, 136.41, 129.77, 129.59, 129.45, 128.98,

126.83, 123.73, 122.96, 121.46, 118.04, 117.89, 116.39, 116.25, 90.07-89.56 (q, JC-F = 255 Hz); 19F NMR (400

MHz, CDCl3) δ = -71.12, -77.50 (s, 3F), -134.25-134.31 (m), -135.17-135.22 (m) ppm; TOF- HRMS (ESI, m/z)

[M+Na]+ calcd for C17H9ClF5NO2Na: 412.0140, found 412.0123.

(iii). (Z)-3-(4-chlorophenyl)-5-(trifluoromethyl)-5-(3-(trifluoromethyl)phenyl)furan-2(5H)-one oxime (4c);



cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.87–7.86 (m, 2 H), 7.72–7.70 (m, 3H), 7.63-7.59 (m, 1H), 7.40-

7.38 (m, 2H), 7.18 (s, 1H), 7.08 (s, 1H, =CH-).; 13C NMR (125 MHz, CDCl3, ppm): δ = 157.04, 136.71,

136.41, 133.85, 131.37, 129.93, 129.75, 129.63, 129.48, 128.98, 128.77, 124.73, 123.78, 123.36, 122.57,

121.51, 90.52-89.73 (q, JC-F = 260 Hz); 19F NMR (400 MHz, CDCl3) δ = -62.64, -77.40 (s, 3F) ppm; TOF-

HRMS (ESI, m/z) [M+Na]+ calcd for C18H10ClF6NO2Na: 444.0202 found 444.0189.

(iv). (Z)-3,5-bis(4-chlorophenyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4d);



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cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.71–7.70 (m, 2H), 7.58–7.56 (m, 2H), 7.44-7.43 (m, 2H), 7.39-

7.37 (m, 2H), 7.03 (s, 1H), 6.91 (s, 1H, =CH-).; 13C NMR (125 MHz, CDCl3, ppm): δ = 157.24, 136.29,

136.12, 131.18, 130.24, 129.44, 129.19, 128.96, 127.90, 126.99, 123.84, 121.57; 119.31, 90.62-90.11 (q, JC-F =

255 Hz); 19F NMR (400 MHz, CDCl3) δ = -77.44 (s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+Na]+ calcd for

C17H10Cl2F3NO2Na: 409.9938, found 409.9934.

(v). (Z)-3-(4-chlorophenyl)-5-(p-tolyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4e);


82%; Melting point: 139-141 °C; FTIR (KBr): νmax = 3403, 2362, 1684, 1338, 1192, 1172, 1035, 987, 820, 763,

684 cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.71–7.69 (m, 2 H), 7.52–7.50 (m, 2H), 7.38-7.36 (m, 2H),

7.27-7.25 (m, 2H), 7.07 (s, 1H, =CH-), 2.38 (s, 3H, -CH3); 13C NMR (125 MHz, CDCl3, ppm): δ = 157.62,

139.94, 136.05, 135.76, 131.05, 129.70, 129.59, 129.44, 128.88, 127.26, 126.35, 91.29-90.82 (q, JC-F = 235 Hz),

21.22; 19F NMR (400 MHz, CDCl3) δ = -77.47 (s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+Na]+ calcd for

C18H12ClF3NO2Na: 389.0406, found 389.0422.

(vi). (Z)-3-(4-chlorophenyl)-5-(4-methoxyphenyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4f);



684 cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.73–7.69 (m, 2 H), 7.56–7.52 (m, 2H), 7.39-7.35 (m, 2H),

7.07-6.94 (m, 2H), 6.8 (s, 1H, =CH-), 3.82 (s, 3H, -OCH3); 13C NMR (125 MHz, CDCl3, ppm): δ = 160.63,

157.63, 136.05, 135.76, 131.00, 129.44, 128.88, 127.93, 127.27, 124.61, 124.09, 114.27, 90.41, 55.42; 19F NMR

(400 MHz, CDCl3) δ = -77.59 (s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+Na]+ calcd for C18H13ClF3NO3Na:

406.0434, found 406.0413.

(vii). (Z)-3-(4-chlorophenyl)-5-(thiophen-2-yl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4g);



684 cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.95 (m, 2H), 7.76-7.72 (m, 2H), 7.44-7.35 (m, 3H), 7.11-

7.06 (m, 1H), 6.95 (s, 1H, =CH-); 13C NMR (125 MHz, CDCl3, ppm): δ = 157.42, 137.66, 134.48, 130.34,

130.17, 128.75, 128.58, 128.13, 127.72, 127.45, 125.43, 119.78, 89.91, 89.91-87.57 (q, JC-F = 675 Hz); 19F

NMR (400 MHz, CDCl3) δ = -77.43 (s, 3F) ppm; TOF- HRMS (ESI, m/z) [M+Na]+ calcd for

C15H9ClF3NO2SNa: 381.9892, found 381.9900.

4.3. Characterization data of trifluoromethyl ketone (TFMK) products with 2c:

(i). (Z)-5-(4-chlorophenyl)-3-(4-fluorophenyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4h);



686 cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.77-7.74 (m, 2H), 7.58-7.57 (m, 2H), 7.44-7.42 (m, 2H),

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7.11-7.08 (m, 2H), 6.95 (s, 1H, =CH-); 13C NMR (125 MHz, CDCl3, ppm): δ = 164.73, 162.73, 157.38,

136.29, 136.06, 131.26, 130.18, 130.12, 129.66, 129.15, 127.87, 124.69, 123.86, 121.59, 115.86, 115.69, 90.26-

89.76 (q, JC-F = 250 Hz); 19F NMR (400 MHz, CDCl3) δ = -77.48 (s, 3F), -109.77-109.84 (m) ppm; TOF- HRMS

(ESI, m/z) [M+H]+ calcd for C17H11ClF4NO2: 372.0414, found 372.0421.

(ii). (Z)-5-(3-fluorophenyl)-3-(4-fluorophenyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4i);



680 cm-1; 1H NMR (500MHz, CDCl3, ppm): = 7.76-7.73 (m, 2H), 7.44-7.37 (m, 3H), 7.28-7.25 (m, 1H),

7.15-7.08 (m, 3H), 6.98 (s, 1H, =CH-); 13C NMR (125 MHz, CDCl3, ppm): δ = 164.75, 163.77, 162.75,

157.36, 136.35, 135.01, 134.96, 130.61, 130.55, 130.18, 129.76, 124.68, 123.84, 122.11, 116.93, 116.77,

115.91, 114.06, 90.44-89.68 (q, JC-F = 255 Hz); 19F NMR (400 MHz, CDCl3) δ = -77.34 (s, 3F), -109.76-109.63

(m), -110.91-110.96 (m) ppm; TOF- HRMS (ESI, m/z) [M+H]+ calcd for C17H11ClF5NO2: 381.0710, found

356.0707.

4.4. 1H and 13C-NMR spectra of trifluoromethylketones products with 2a:

(i). (Z)-5-(4-fluorophenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3a);

ppm (t1)0.05.0

0

500000000

1000000000

1500000000

7.7397.7347.7277.720

7.6497.6397.6327.6227.4217.4167.4097.2057.1597.1427.043

1.668

-0.000000

0.84

0.90

2.08

2.85

1.89

2.10

OF3CN

HO

F

S8

ppm (t1)050100150

0

100000000

200000000

300000000

400000000

500000000

600000000

164.405162.418157.582

137.419130.345130.091

128.703128.567128.067123.967121.704

116.005115.831

90.62390.36590.10889.848

OF3CN

HO

F

HRMS of compound (3a)

19F NMR spectra of product (3a)

S9

(ii). (Z)-5-(3-fluorophenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3b);

ppm (t1)0.05.010.0

0

500000000

7.7307.7147.6977.6837.629

7.4247.4117.3947.1317.1187.102

7.007

1.789

-0.001

1.00

0.91

1.94

0.92

5.34

OF3CN

HO

F

ppm (t1)050100150

0

50000000

100000000

150000000

160.480

155.557152.701

132.790130.410130.264125.853125.692125.391

123.980123.311117.401115.161112.230111.813109.473108.993

86.33985.66985.03884.39772.90972.27471.639

OF3CN

HO

F

HRMS of compound (3b)

S10

19F NMR spectra of product (3b)

S11

(iii). (Z)-5-(3,4-difluorophenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3c);

ppm (t1)0.05.010.0

0

500000000

1000000000

1500000000

7.7727.7597.7417.7237.5437.5367.4647.4507.4337.3947.3357.2917.2487.2047.015

1.761

0.028

1.00

2.23

1.11

5.05

OF3CN

HO

F

F

ppm (t1)050100150

0

50000000

157.276

153.781153.503153.028152.738148.733148.453148.014147.725137.744

130.233129.777129.617128.724128.438128.069125.477122.966119.806

117.890117.809

116.30990.62289.97689.33488.68377.65277.01776.382

OF3CN

HO

F

F

HRMS of compound (3c)

S12

19F NMR spectra of product (3c)

(iv). (Z)-3-phenyl-5-(trifluoromethyl)-5-(3-(trifluoromethyl)phenyl)furan-2(5H)-one oxime (3d);

ppm (t1)0.05.010.0

0

500000000

1000000000

1500000000

8.2687.9257.9107.8947.7247.7147.692

7.5927.5767.4067.079

0.019

1.00

1.15

2.23

1.04

3.13

3.06

OF3CN

HO

F3C

S13

ppm (t1)050100150

0

100000000

200000000

300000000

400000000

500000000

600000000

700000000157.363138.036134.025131.789131.528131.268131.008130.250130.039129.762129.541128.781128.489128.090

126.632124.794123.882123.406122.628121.61590.58290.32690.07089.81077.30277.04876.793

OF3CN

HO

F3C

HRMS of compound (3d)

19F NMR spectra of product (3d)

S14

(v). (Z)-5-(4-chlorophenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3e);

ppm (t1)0.05.0

0

500000000

1000000000

1500000000

7.7127.7057.5907.5737.4247.408

7.017

1.770

1.00

5.00

2.02

1.96

OF3CN

HO

Cl

ppm (t1)050100150

0

100000000

200000000

300000000

400000000

500000000

157.497

137.504

135.982131.364130.127129.097128.708128.601128.069127.925123.895121.632

90.53090.33190.07289.814

OF3CN

HO

Cl

HRMS of compound (3e)

S15

19F NMR spectra of product (3e)

(vi). (Z)-3-phenyl-5-(thiophen-2-yl)-5-(trifluoromethyl)furan-2(5H)-one oxime (3f);

ppm (t1)0.05.010.0

0

500000000

1000000000

1500000000

7.7267.7097.6967.4277.4097.3537.3377.0927.0677.048

6.942

-0.000000

1.00

1.12

5.34

2.20

S

O NF3C

HO

ppm (t1)050100150

0

50000000

100000000157.424

137.664

134.484130.344130.176

128.755128.583128.135127.723127.457125.438119.782

89.91689.23988.57487.906

77.70277.06676.431

S

O NF3C

HO

S16

HRMS of compound (3f)

19F NMR spectra of product (3f)

(vii). (Z)-3,5-diphenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3g);

ppm (t1)0.05.0

0

500000000

1000000000

7.6487.6417.6347.5787.564

7.3727.3587.3327.3257.301

6.993

1.626

0.80

1.581.635.67

OF3CN

HO

S17

ppm (t1)050100150

0

100000000

200000000

300000000

400000000

500000000

600000000

700000000

800000000

157.821

137.204132.875130.826130.060129.749128.892128.741128.127

126.532124.132121.866

91.09190.83390.57990.32677.34777.09376.839

OF3CN

HO

HRMS of compound (3g)

19F NMR spectra of product (3g)

S18

(viii). (Z)-5-(4-methoxyphenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3h);

ppm (t1)0.05.0

0

100000000

200000000

300000000

400000000

500000000

600000000

700000000

7.7517.7347.7177.7047.5787.5347.4167.4017.3857.1467.056

6.9796.935

3.820

1.666

-0.004

1.89

0.93

0.93

1.94

2.86

1.98

3.00

OF3CN

HO

MeO

ppm (t1)050100150

0

100000000

200000000

300000000

400000000

500000000

160.545157.883

136.940130.820129.919128.879128.623128.074127.944124.823

114.202

90.85490.60490.35790.100

55.366

OF3CN

HO

MeO

HRMS of compound (3h)

S19

19F NMR spectra of product (3h)

(ix). (Z)-5-(2,4-dimethoxyphenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3i);

ppm (t1)0.05.0

0

500000000

10000000007.8057.7627.7357.725

7.6207.4357.4177.405

6.6326.6216.5776.544

3.9033.848

1.289

0.032

2.99

3.52

0.99

0.85

2.75

2.72

OF3CN

HO

MeOOMe

ppm (t1)50100150

0

10000000

20000000

30000000

40000000

50000000

60000000

70000000

80000000

162.064157.814

135.707132.220129.938129.556129.403128.521128.063125.965120.274113.611104.921

99.461

91.16290.50489.84289.18877.65377.01876.383

55.75655.457

OF3CN

HO

MeOOMe

S20

HRMS of compound (3i)

19F NMR spectra of product (3i)

(x). (Z)-5-(4-methylphenyl)-3-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (3j);

ppm (t1)0.05.010.0

0

100000000

200000000

300000000

400000000

500000000

600000000

700000000

8000000007.7257.7187.7147.5347.5187.4087.4027.3967.2627.247

7.061

2.373

1.663

3.00

0.91

2.23

2.94

1.99

1.95

0.77

OF3CN

HO

Me

S21

ppm (t1)050100150

0

100000000

200000000

300000000

400000000

157.870

139.776136.943130.852129.908129.492128.869128.615128.071

126.372124.122121.860

91.02290.75490.49890.276

77.26677.01276.758

21.157

OF3CN

HO

Me

HRMS of compound (3j)

19F NMR spectra of product (3j)

S22

4.5. 1H and 13C-NMR spectra of trifluoromethylketone products with 2b:

(i). (Z)-3-(4-chlorophenyl)-5-phenyl-5-(trifluoromethyl)furan-2(5H)-one oxime (4a);

ppm (t1)0.05.010.0

0

500000000

1000000000

1500000000

7.7057.6887.6477.634

7.4627.4487.3867.3697.257

7.187

7.087

0.000

1.00

1.00

2.04

3.05

2.01

1.97

ON

F3C

HO

Cl

ppm (t1)050100150200

0

50000000

100000000

150000000

200000000

250000000

300000000

350000000

157.530

136.125135.971

132.655

130.951129.818129.446128.926

127.199126.455124.028121.760

116.20991.08490.82690.56990.31277.32077.06676.812

ON

F3C

HO

Cl

HRMS of compound (4a)

S23

19F NMR spectra of product (4a)

(ii). (Z)-3-(4-chlorophenyl)-5-(3,4-difluorophenyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4b);

ppm (t1)0.05.010.0

0

500000000

7.7147.6977.5237.5197.5037.4877.483

7.4007.3827.369

7.2877.2707.2627.2527.2347.099

7.001

1.656

1.00

1.01

1.34

3.03

1.04

0.88

0.96

O

NHO

F3CCl

FF

ppm (t1)050100150200

0

100000000

200000000

300000000

400000000

500000000

157.017152.269152.156151.507151.389150.245150.134149.496149.376136.557136.413

129.773129.597129.453128.988

126.835123.734122.961

121.465118.044117.899

116.390116.25190.07189.82189.56389.18277.31277.05876.804

0.026

O

NHO

F3CCl

FF

S24

HRMS of compound (4b)

19F NMR spectra of product (4b)

S25

ppm (t1)0.05.010.0

0

500000000

1000000000

7.8787.866

7.7267.7087.6317.6147.5987.4027.384

7.2617.184

7.083

1.683

-0.00000

1.00

0.97

1.98

3.04

1.01

2.02

OF3CN

HO

F3C

Cl

(iii). (Z)-3-(4-chlorophenyl)-5-(trifluoromethyl)-5-(3-(trifluoromethyl)phenyl)furan-2(5H)-one oxime (4c);

ppm (t1)050100150

0

100000000

200000000

300000000

400000000

157.041136.714136.417133.851131.634131.371

129.931129.757129.632129.487128.986126.855126.773124.738123.783123.364122.573

121.515

90.52190.26090.00089.738

77.31177.05776.803

OF3CN

HO

F3C

Cl

S26

HRMS of compound (4c)

19F NMR spectra of product (4c)

(iv). (Z)-3,5-bis(4-chlorophenyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4d);

ppm (t1)0.05.010.0

0

100000000

200000000

300000000

400000000

500000000

600000000

700000000

7.7187.701

7.5877.569

7.4497.4327.3947.376

7.262

7.037

6.919

5.301

1.612

0.00000

1.00

1.02

2.11

2.07

2.04

2.14

OF3CN

HO

ClCl

S27

ppm (t1)050100150200

0

100000000

200000000

300000000

400000000

500000000

600000000

157.246

136.296136.125131.180130.241129.446129.199128.961127.905126.991123.844121.578119.31690.62990.36990.11489.852

ON

F3C

HO

Cl

Cl

HRMS of compound (4d)

19F NMR spectra of product (4d)

S28

(v). (Z)-3-(4-chlorophenyl)-5-(p-tolyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4e);

ppm (t1)0.05.010.0

0

500000000

1000000000

1500000000

20000000007.7137.697

7.5247.5087.3847.367

7.2717.258

7.075

2.380

1.602

0.00000

2.09

2.11

2.03

2.54

1.00

3.17

ON

F3C

HO

Cl

ppm (t1)050100150

0

100000000

200000000

300000000

400000000

500000000

600000000

157.626

139.948

136.059135.766131.058

129.701129.591129.442128.885

127.264126.359

91.29191.12390.82190.561

77.30977.05576.801

21.224

0.031

ON

F3C

HO

Cl

HRMS of compound (4e)

S29

19F NMR spectra of product (4e)

(vi). (Z)-3-(4-chlorophenyl)-5-(4-methoxyphenyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4f);

ppm (t1)0.05.010.0

0

500000000

1000000000

7.7357.693

7.5697.527

7.3977.356

7.2607.070

6.9876.945

6.847

3.829

1.602

-0.001

2.80

1.72

1.80

1.62

0.77

2.53

OF3CN

HO

ClMeO

ppm (t1)050100150

0

100000000

200000000

300000000

400000000

160.634157.633

136.051135.761131.009

129.444128.881127.930127.278124.616124.090114.279

90.410

55.424

0.034

OF3CN

HO

ClMeO

S30

HRMS of compound (4f)

19F NMR spectra of product (4f)

(vii). (Z)-3-(4-chlorophenyl)-5-(thiophen-2-yl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4g);

ppm (t1)0.05.0

0

500000000

1000000000

1500000000

7.8727.8637.7547.7377.4427.4327.3927.3757.3497.342

7.265

7.0997.0897.0826.954

0.00000

1.00

0.99

0.99

2.04

1.01

2.04

0.99

S

O

N

F3C

HO

Cl

S31

ppm (t1)050100150200

0

100000000

200000000

300000000

400000000156.880

136.400136.194

134.518

130.086129.571128.867127.727127.509127.099123.710123.668

121.445

89.32289.15988.89388.624

77.32077.06576.812

0.033

S

O

N

F3C

HO

Cl

HRMS of compound (4g)

19F NMR spectra of product (4g)

S32

4.6. 1H and 13C-NMR spectra of trifluoromethylketone products with 2c:

(i). (Z)-5-(4-chlorophenyl)-3-(4-fluorophenyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4h);

ppm (t1)0.05.010.0

0

500000000

1000000000

1500000000

7.7717.7617.7547.7437.5887.5717.4457.4287.2607.1177.0997.082

6.998

-0.00000

2.00

2.09

2.05

2.06

2.07

ON

HO

FCl

F3C

ppm (t1)050100150200

0

100000000

200000000

300000000

400000000164.731

162.735157.382

136.295136.060131.269130.185130.120129.660129.150127.878124.692123.860121.592

115.867115.694

90.26690.01289.764

77.27877.02476.770

-0.00000

ON

HO

FCl

F3C

HRMS of compound (4h)

S33

19F NMR spectra of product (4h)

(ii). (Z)-5-(3-fluorophenyl)-3-(4-fluorophenyl)-5-(trifluoromethyl)furan-2(5H)-one oxime (4i);

ppm (t1)0.05.010.0

0

1000000000

2000000000

3000000000

4000000000

7.7627.7517.7457.7347.4427.4267.4207.3907.371

7.2577.251

7.1567.1387.1257.1197.1027.084

6.989

-0.0000

1.00

3.06

1.12

3.03

2.00

O

NHO

FF3C

F

S34

ppm (t1)050100150

0

100000000

200000000

300000000

400000000

500000000

600000000

700000000

800000000

900000000

164.751163.777162.754161.808157.367136.357

135.016134.960130.617130.554130.183130.118129.764124.681123.847

122.118116.938116.772115.911115.738

114.060113.869

90.44690.19789.94389.68477.28877.03476.780

-0.000

O

NHO

FF3C

F

HRMS of compound (4i)

19F NMR spectra of product (4i)

S35

5. References:

1. A. J. N. Martin, L Ozores and B. List, J. Am. Chem. Soc., 2007, 129, 8976.

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