highly regio-, diastereo- and enantioselective one-pot ... · s3 table s2. optimization of the...

S1

Electronic Supplementary Information

Highly regio-, diastereo- and enantioselective one-pot

gold/chiral Brønsted acid-catalysed cascade synthesis of

bioactive diversely substituted tetrahydroquinolines

Xin-Yuan Liu,† Ya-Ping Xiao, † Fung-Ming Siu, Li-Chen Ni, Yong Chen, Lin Wang

and Chi-Ming Che*

Department of Chemistry, State Key Laboratory of Synthetic Chemistry, and Open

Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug

Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong

(P. R. China) † These authors contributed equally.

[email protected]

Table of Contents

Table S1 S2

Table S2

Chart S1

S3

S3

NMR spectra of new compounds S4

HPLC spectra S42

Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

S2

Table S1. Optimization of the reaction conditions for the one-pot gold/chiral Brønsted acid-catalysed cascade reactionsa

+NH

Cl

3Aa2a

CHO

NH2

Cl

1A

1) (tBu)2(o-diphenyl)PAu(CH3CN)X, 5 Å MS60 °C, 6 h

NH

O

OEt

OEtO

2) 4 (2.5 equiv.), 5a (y mol%), 60 °C, 20 h

4

O

OP OH

O

5a Entry (tBu)2(o-diphenyl)PAu(C

H3CN)X (X =) y Solvent Yield (%)b ee (%)c

1d SbF6- (3 mol %) 10 benzene 87 90

2 SbF6- (3 mol %) 10 benzene 89 97

3 OTf- (3 mol %) 10 benzene 70 96 4 BF4

- (3 mol %) 10 benzene 56 97 5 SbF6

- (2 mol %) 5 benzene 89 97 6 SbF6

- (2 mol %) 3 benzene 90 97 7 SbF6

- (2 mol %) 2 benzene 86 97 8 SbF6

- (1 mol %) 2 benzene 50 97 9 SbF6

- (2 mol %) 3 toluene 93 94 10 SbF6

- (2 mol %) 3 THF 76 93 11 SbF6

- (2 mol %) 3 CH2Cl2 27 91 12 SbF6

- (2 mol %) 3 CH3CN <5 --e a Reaction conditions: 2-amino-5-chlorobenzaldehyde (1A) (0.2 mmol), phenylacetylene (2a) (0.24 mmol), ethyl Hantzsch ester (0.5 mmol), (tBu)2(o-diphenyl)PAu(CH3CN)X, 5a, solvent (3 mL), 5 Å MS (0.5 g), 60 oC. 5a = (R)-3,3’-bis(9-phenanthryl)-1,1’-binaphthalene-2,2’-diyl hydrogen phosphate. b Isolated yield based on 1A. c Determined by HPLC analysis on a chiral phase (Chiralcel OD-H); configuration assigned by comparison with the literature. d

Reaction conditions: 2-amino-5-chlorobenzaldehyde (1A) (0.2 mmol), phenylacetylene (2a) (0.24 mmol), ethyl Hantzsch ester (0.5 mmol), (tBu)2(o-diphenyl)PAu(CH3CN)X, 5a, solvent (3 mL), 60 oC. e No detection.


S3

Table S2. Optimization of the reaction conditions for diastereo- and enantioselective synthesis of 2,4-disubstituted tetrahydroquinolinea

Entry R Phosphoric acid Yield (%)b d.r.c ee (%)d 1 Et (R)-5a 75 1:1.3 65 2 Et (R)-5b 78 1:1.2 40 4 Et (S)-5c 76 1:2 73 3 Et (R)-5e 73 20:1 86 5 tBu (R)-5e 57 20:1 70

a Reaction conditions: 2-aminobenzophenone (0.2 mmol), 4-ethynylbiphenyl (0.24 mmol), ethyl Hantzsch ester (0.5 mmol), (tBu)2(o-diphenyl)PAu(CH3CN)SbF6 (3 mol%), 5 (5 mol%), benzene (4 mL), 5 Å MS (0.5 g). b Isolated yield based on 2-aminobenzophenone. c Diastereomeric ratio determined by 1H NMR spectroscopy. d

Determined by chiral HPLC analysis.

Chart S1. Structures of 3Lb and 3Lb’.

NH

OMe3Lb

NH

OMe3Lb'

ee: >99% ee: >99%


S4

ppm (f1)-1.00.01.02.03.04.05.06.07.0

7.32

57.

296

7.26

36.

991

6.96

26.

955

6.94

66.

936

6.90

8

6.46

66.

439

4.39

84.

388

4.36

74.

357

4.07

44.

031

3.83

73.

809

2.95

42.

936

2.91

92.

900

2.88

12.

864

2.84

62.

760

2.74

42.

728

2.70

52.

689

2.67

32.

140

2.12

52.

113

2.11

02.

097

2.08

12.

070

2.05

32.

016

1.99

91.

983

1.96

71.

955

1.95

01.

941

1.93

31.

924

1.90

61.

889

2.02

4.00

1.00

1.00

0.993.04

1.041.03

2.10

NH

Cl

3Ab OMe

ppm (f1)50100150

159.

059

143.

415

136.

456

128.

859

127.

600

126.

673

122.

408

121.

380

114.

946

114.

001

77.5

3976

.694

55.6

1055

.341

30.6

20

26.3

62

NH

Cl

3Ab OMe


S5

ppm (f1)1.02.03.04.05.06.07.0

7.30

57.

285

7.26

56.

977

6.95

16.

940

6.86

16.

841

6.47

36.

453

4.41

74.

411

4.39

54.

389

4.06

7

3.82

02.

919

2.90

52.

893

2.87

82.

864

2.85

22.

838

2.73

62.

724

2.71

22.

695

2.68

22.

671

2.15

12.

140

2.13

02.

119

2.10

72.

098

2.01

22.

000

1.98

81.

976

1.96

51.

953

1.94

41.

931

1.91

81.13

3.870.82

1.00

1.09

1.05

3.30

1.171.16

1.171.17

NH

Cl

3Ac

OMe

ppm (f1)050100150

159.

894

146.

123

143.

206

129.

645

128.

837

126.

696

122.

381

121.

470

118.

788

114.

943

112.

796

112.

130

77.3

7677

.059

76.7

42

56.0

8355

.249

30.4

55

26.1

59

NH

Cl

3Ac

OMe


S6

ppm (f1)-1.00.01.02.03.04.05.06.07.0

7.48

67.

467

7.26

47.

245

7.23

67.

215

7.20

37.

004

6.97

46.

495

6.46

8

4.70

24.

692

4.67

24.

662

3.97

62.

963

2.94

52.

928

2.90

82.

890

2.87

32.

855

2.78

52.

769

2.75

32.

730

2.71

42.

698

2.41

02.

163

2.14

72.

135

2.12

02.

104

2.09

22.

076

1.97

21.

955

1.93

81.

925

1.90

91.

893

1.88

21.

865

1.84

7

1.00

2.96

1.85

0.96

0.97

0.93

0.960.99

2.93

1.041.08

NH

Cl

3Ad

CH3

ppm (f1)050100

143.

600

142.

179

134.

719

130.

605

128.

864

127.

199

126.

708

126.

456

125.

909

122.

323

121.

350

114.

925

77.4

8977

.064

76.6

41

52.1

21

28.7

19

26.3

24

19.0

61

NH

Cl

3Ad

CH3


S7

ppm (f1)0.01.02.03.04.05.06.07.0

7.28

87.

268

7.20

27.

182

6.98

76.

963

6.95

7

6.46

76.

446

4.41

54.

407

4.39

24.

384

4.03

02.

932

2.91

92.

906

2.89

22.

878

2.86

52.

851

2.74

82.

736

2.72

42.

706

2.69

42.

682

2.38

52.

141

2.12

92.

120

2.10

82.

096

2.08

82.

075

2.01

11.

999

1.98

81.

985

1.97

51.

966

1.96

21.

955

1.95

21.

949

1.94

31.

929

1.91

72.041.89

1.71

1.00

1.03

0.95

1.171.14

3.17

1.141.10

NH

Cl

3Ae CH3

ppm (f1)50100

143.

359

141.

397

137.

241

129.

302

128.

844

126.

672

126.

389

122.

395

121.

386

114.

903

109.

973

77.3

7877

.061

76.7

43

55.8

96

31.5

43

30.5

2230

.185

29.7

38

26.2

7121

.112

NH

Cl

3Ae CH3


S8

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.63

47.

624

7.61

77.

604

7.49

77.

478

7.46

67.

446

7.40

37.

385

7.36

67.

260

7.01

26.

990

6.50

16.

481

4.50

04.

492

4.47

74.

470

4.09

52.

955

2.94

22.

930

2.91

52.

901

2.88

82.

875

2.77

62.

764

2.75

22.

735

2.72

32.

711

2.19

92.

187

2.17

82.

166

2.15

42.

146

2.13

4

2.06

82.

056

2.04

32.

033

2.02

02.

009

2.00

01.

987

1.97

5

4.053.970.87

1.72

1.00

1.03

0.99

1.061.10

1.071.12

NH

Cl

3Af Ph

ppm (f1)050100

143.

439

143.

242

140.

764

140.

548

128.

895

128.

834

127.

363

127.

078

126.

933

126.

750

122.

409

121.

540

114.

992

77.3

8977

.071

76.7

54

55.8

46

30.4

67

26.1

66

NH

Cl

3Af Ph


S9

ppm (f1)0.05.0

7.36

27.

356

7.33

37.

326

7.31

87.

311

7.30

27.

296

7.28

77.

280

7.26

06.

970

6.95

26.

946

6.47

86.

473

6.46

06.

456

4.42

54.

417

4.40

24.

394

4.02

6

2.90

02.

887

2.87

52.

859

2.84

52.

833

2.82

02.

705

2.69

32.

681

2.66

42.

652

2.63

92.

117

2.10

82.

104

2.09

52.

091

2.08

42.

076

2.07

12.

063

2.05

82.

050

1.96

61.

953

1.94

31.

940

1.93

31.

930

1.92

71.

920

1.91

81

910

187

2

3.73

1.69

1.00

1.04

0.89

1.161.17

1.181.17

NH

Cl

3Ag Cl

ppm (f1)50100

142.

937

142.

877

133.

155

128.

856

128.

735

127.

803

126.

762

122.

281

121.

747

115.

008

77.3

1476

.998

76.6

81

55.4

57

30.4

56

25.8

95

NH

Cl

3Ag Cl


S10

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.63

57.

615

7.50

77.

487

7.26

06.

993

6.98

56.

978

6.97

26.

513

6.50

36.

500

6.49

0

4.53

14.

523

4.50

94.

501

4.09

22.

917

2.90

32.

892

2.87

62.

862

2.85

02.

837

2.71

12.

698

2.68

52.

669

2.65

62.

644

2.17

12.

158

2.14

92.

137

2.12

52.

116

2.10

32.

015

2.00

21.

992

1.99

01.

980

1.97

71.

968

1.95

61.

947

1.93

51.

922

1.801.95

1.67

0.98

1.00

0.98

1.081.10

1.081.11

NH

Cl

3Ah CF3

ppm (f1)50100150

148.

478

142.

794

129.

943

129.

622

128.

902

126.

852

126.

811

125.

600

125.

563

122.

289

121.

892

115.

119

77.3

5977

.041

76.7

24

55.6

43

30.3

47

25.7

24

NH

Cl

3Ah CF3


S11

ppm (f1)-1.00.01.02.03.04.05.06.07.08.0

7.64

57.

634

7.62

57.

484

7.46

37.

271

7.26

06.

992

6.98

66.

969

6.52

26.

513

6.50

76.

496

6.49

0

4.53

14.

522

4.51

04.

501

4.09

82.

888

2.87

52.

864

2.84

92.

834

2.82

32.

810

2.67

22.

659

2.64

62.

631

2.61

82.

604

2.15

32.

144

2.14

02.

131

2.12

62.

120

2.11

72.

111

2.10

72.

098

2.09

32.

084

1.98

21.

969

1.96

01.

958

1.94

81.

937

1.92

51.

915

1.90

41.

891

1.762.00

1.69

1.00

1.03

0.88

1.111.13

1.121.14

NH

Cl

3Ai CN

ppm (f1)050100150

149.

950

142.

526

132.

469

128.

899

127.

229

126.

922

126.

827

126.

801

122.

176

122.

040

118.

772

115.

187

111.

274

77.4

9177

.068

76.6

46

55.5

87

31.5

1730

.182

29.7

0525

.469

NH

Cl

3Ai CN


S12

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.75

57.

728

7.70

5

7.46

37.

460

7.44

27.

439

7.26

0

7.18

47.

178

7.16

27.

152

6.99

76.

979

6.97

3

6.49

76.

476

4.55

54.

547

4.53

24.

524

4.12

43.

932

2.94

52.

932

2.91

92.

905

2.89

12.

878

2.86

42.

753

2.74

22.

730

2.71

22.

700

2.68

92.

193

2.18

12.

172

2.16

12.

149

2.14

02.

128

2.08

92.

077

2.06

52.

053

2.04

12.

029

2.02

12.

008

1.99

5

2.97

0.98

1.931.71

0.97

1.00

0.963.16

1.041.05

1.031.08

NH

Cl

3Aj OMe

ppm (f1)50100150

157.

683

143.

315

139.

437

134.

098

129.

306

128.

864

128.

813

127.

252

126.

710

125.

207

124.

956

122.

459

121.

445

119.

038

114.

953

105.

687

77.3

6877

.050

76.7

33

56.1

4755

.328

30.4

71

26.2

66

NH

Cl

3Aj OMe


S13

ppm (f1)0.01.02.03.04.05.06.07.0

7.29

47.

273

7.26

06.

918

6.91

16.

889

6.60

96.

604

6.58

96.

584

6.50

16.

496

4.39

74.

389

4.37

44.

366

4.05

83.

820

2.88

72.

874

2.86

12.

847

2.83

32.

820

2.80

72.

722

2.71

02.

698

2.68

12.

669

2.65

72.

116

2.10

32.

095

2.08

32.

071

2.06

22.

050

1.97

91.

967

1.95

31.

943

1.93

41.

930

1.91

71.

911

1.89

71.

885

2.00

2.81

0.790.84

1.00

0.93

3.07

1.071.09

1.081.09

NH

3Bb OMe

Cl

ppm (f1)050100150

159.

040

145.

708

136.

335

132.

073

130.

189

127.

550

119.

174

116.

758

113.

987

113.

275

77.3

6777

.049

76.7

32

55.4

0755

.325

30.7

12

25.9

08

NH

3Bb OMe

Cl


S14

ppm (f1)-1.00.01.02.03.04.05.06.07.08.0

7.31

17.

290

7.26

0

6.95

26.

932

6.92

06.

914

6.89

86.

740

6.72

16.

439

6.41

94.

343

4.33

64.

319

4.31

24.

103

3.82

62.

954

2.94

12.

930

2.91

12.

898

2.88

72.

861

2.84

72.

835

2.82

02.

804

2.79

22.

777

2.17

42.

165

2.15

72.

151

2.14

12.

132

2.12

42.

118

2.10

92.

011

1.99

71.

985

1.97

81.

971

1.96

11.

953

1.94

61.

939

1.92

81.

913

2.02

2.920.81

1.00

1.040.93

3.18

1.101.13

1.131.13

NH

3Cb OMe

Cl

ppm (f1)050100150

159.

071

146.

393

136.

168

134.

734

127.

614

127.

279

118.

826

117.

695

114.

003

112.

361

77.3

7277

.054

76.7

36

55.3

3055

.188

30.7

73

24.4

60

NH

3Cb OMe

Cl


S15

ppm (f1)0.05.0

7.31

07.

281

7.27

27.

261

7.11

77.

108

7.08

07.

072

6.93

46.

924

6.91

86.

895

6.88

66.

416

6.38

84.

391

4.38

04.

360

4.34

94.

065

4.03

43.

849

3.82

83.

800

3.79

62.

944

2.92

52.

909

2.88

92.

871

2.85

42.

835

2.74

92.

733

2.71

72.

694

2.67

82.

662

2.12

82.

112

2.10

02.

084

2.06

92.

057

2.04

02.

001

1.98

41.

966

1.95

31.

940

1.93

51.

926

1.92

21.

918

1.90

91

874

2.041.951.98

1.00

0.99

0.962.96

1.021.03

1.021.06

NH

Br

3Db OMe

ppm (f1)050100150

159.

053

143.

831

136.

400

131.

691

129.

520

127.

588

122.

940

115.

382

114.

001

108.

432

77.1

0876

.685

55.5

3655

.350

30.5

40

26.2

77

NH

Br

3Db OMe


S16

ppm (f1)0.05.0

7.33

67.

315

6.93

06.

909

6.76

46.

743

6.72

56.

719

6.47

96.

467

6.46

06.

456

6.44

34.

359

4.35

24.

335

4.32

83.

912

3.89

33.

834

3.78

12.

978

2.96

42.

951

2.93

72.

923

2.90

92.

895

2.77

02.

759

2.74

82.

729

2.71

72.

706

2.11

52.

108

2.10

22.

092

2.08

32.

076

2.06

92.

060

2.01

72.

004

1.99

11.

979

1.96

51.

959

1.95

31.

947

1.93

31.

920

1.96

1.901.84

0.96

1.00

0.663.16

1.081.10

1.091.14

NH

F

3Eb OMe

ppm (f1)050100150

159.

016

156.

682

154.

349

141.

103

136.

644

127.

631

122.

214

122.

149

115.

532

115.

317

114.

677

114.

601

113.

958

113.

457

113.

234

77.4

1077

.093

76.7

74

55.8

2755

.315

30.8

34

26.7

35

NH

F

3Eb OMe


S17

ppm (f1)0.05.0

7.32

07.

313

7.30

87.

296

7.29

17.

284

7.26

07.

092

7.07

36.

938

6.93

06.

925

6.91

46.

909

6.90

16.

887

6.86

86.

741

4.44

54.

437

4.42

24.

413

4.18

7

3.82

92.

975

2.96

22.

949

2.93

42.

920

2.90

72.

894

2.81

22.

800

2.78

92.

771

2.75

92.

747

2.15

62.

144

2.13

52.

132

2.12

32.

112

2.10

32.

090

2.01

92.

007

1.99

61.

993

1.98

41.

981

1.97

41.

970

1.96

31.

960

1.95

71

951

2.181.083.021.00

1.131.05

3.42

1.211.17

1.201.16

NH

3Fb OMe

F3C

ppm (f1)050100150

159.

133

144.

849

136.

190

129.

480

129.

407

129.

092

127.

525

125.

784

124.

364

123.

082

114.

049

113.

279

113.

241

110.

145

110.

107

77.3

5277

.033

76.7

16

55.5

1755

.293

30.4

32

26.3

41

NH

3Fb OMe

F3C


S18

ppm (f1)0.05.0

7.70

07.

683

7.67

87.

280

7.27

37.

268

7.25

97.

256

7.25

17.

244

6.90

66.

899

6.89

46.

882

6.87

76.

870

6.47

76.

472

6.45

54.

473

4.46

74.

452

4.44

3

3.84

43.

807

2.92

32.

910

2.89

72.

882

2.86

92.

856

2.84

32.

778

2.76

62.

753

2.73

72.

725

2.71

3

2.12

62.

117

2.10

52.

094

2.08

42.

072

1.98

51.

973

1.96

01.

951

1.94

81.

941

1.93

71.

925

1.91

81.

904

1.89

2

1.73

2.04

1.86

1.00

1.93

2.913.06

1.041.06

1.051.06

NH

MeO2C

3Gb OMe

ppm (f1)050100150

167.

446

159.

131

148.

721

135.

950

131.

127

129.

222

127.

515

119.

678

117.

905

114.

043

112.

670

77.3

4277

.024

76.7

06

55.5

4555

.313

51.4

60

30.3

55

26.0

07

NH

MeO2C

3Gb OMe


S19

ppm (f1)0.05.0

7.34

17.

336

7.31

97.

260

6.92

56.

918

6.91

36.

901

6.89

66.

889

6.85

46.

836

6.48

76.

465

4.37

94.

371

4.35

54.

348

3.89

33.

887

3.82

92.

967

2.95

32.

939

2.92

62.

912

2.89

82.

884

2.76

12.

749

2.73

82.

720

2.70

82.

697

2.25

62.

113

2.10

92.

104

2.10

02.

090

2.08

02.

076

2.07

22.

068

2.05

82.

026

2.01

32.

002

1.99

91.

993

1.98

91.

986

1.98

11.

975

1.97

01.

966

196

21

957

1.92

1.811.92

1.00

1.00

0.883.08

1.091.08

3.151.091.01

NH

H3C

3Ib OMe

ppm (f1)050100150

158.

906

142.

505

137.

061

129.

821

127.

638

127.

388

126.

325

120.

924

114.

115

113.

887

77.3

7077

.053

76.7

35

55.8

7755

.314

31.2

98

26.5

79

20.4

47

NH

H3C

3Ib OMe


S20

ppm (f1)0.05.0

7.30

47.

283

7.27

67.

251

6.90

46.

898

6.89

16.

885

6.87

46.

869

6.86

26.

251

6.24

56.

231

6.22

56.

093

6.08

74.

373

4.36

54.

349

4.34

14.

002

3.80

53.

742

2.84

12.

828

2.81

42.

801

2.70

22.

690

2.67

82.

662

2.65

02.

638

2.08

32.

073

2.06

22.

051

2.04

32.

030

1.98

21.

969

1.95

51.

949

1.94

51.

942

1.93

71.

931

1.92

61.

922

1.91

81.

913

2.12

3.11

1.001.02

1.04

0.903.163.23

1.081.12

1.121.17

NH

3Jb OMe

H3CO

ppm (f1)050100150

158.

938

145.

599

136.

812

129.

897

127.

619

113.

904

113.

540

103.

003

99.2

11

77.3

4577

.028

76.7

10

55.6

8055

.322

55.1

85

31.3

45

25.7

86

NH

3Jb OMe

H3CO


S21

ppm (f1)1.02.03.04.05.06.07.0

7.31

57.

310

7.29

87.

293

7.28

67.

260

6.90

96.

902

6.89

76.

885

6.88

06.

514

6.13

5

5.82

15.

817

5.81

55.

811

4.31

24.

304

4.28

84.

280

3.81

42.

861

2.84

72.

834

2.82

02.

678

2.66

62.

655

2.62

62.

614

2.17

9

2.05

82.

048

2.04

32.

040

2.03

5

1.98

01.

968

1.96

61.

955

1.95

31.

941

1.92

81.99

1.85

0.82

0.85

1.95

1.00

3.02

1.13

1.15

1.111.17

NH

3Kb OMe

O

O

ppm (f1)050100150

158.

943

146.

277

139.

535

139.

410

136.

808

127.

608

113.

905

112.

636

109.

010

100.

259

96.3

66

77.3

4977

.031

76.7

14

55.8

9955

.295

31.5

1131

.232

30.1

5426

.621

NH

3Kb OMe

O

O


S22

ppm (f1)1.02.03.04.05.06.07.0

7.26

47.

256

7.24

57.

239

7.23

07.

126

7.11

87.

108

7.10

27.

014

7.00

87.

002

6.99

76.

992

6.50

76.

495

6.48

4

5.27

9

4.93

84.

927

3.62

13.

220

3.20

93.

206

3.19

43.

183

3.18

03.

168

2.87

22.

847

2.83

4

3.062.011.93

1.00

1.01

0.73

2.99

0.99

2.12

NH

3Ak

Cl CO2Me

ppm (f1)050100150

172.

148

142.

053

141.

624

129.

099

128.

537

128.

402

127.

892

127.

322

126.

758

126.

676

121.

621

120.

322

114.

495

77.3

9077

.071

76.7

53

55.9

0551

.679

42.9

69

24.9

00

NH

3Ak

Cl CO2Me


S23

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.25

67.

249

7.24

47.

235

7.22

3

7.15

37.

141

7.12

97.

121

7.01

07.

003

6.98

96.

981

6.51

46.

504

6.49

36.

483

4.94

44.

930

4.42

04.

109

4.10

24.

085

4.07

84.

061

4.05

54.

043

4.03

74.

031

4.01

93.

199

3.19

33.

179

3.16

53.

160

3.14

52.

886

2.85

32.

841

2.80

5

1.25

41.

204

1.18

01.

156

3.151.941.91

1.00

0.99

0.91

2.01

0.99

2.01

3.13

NH

3Al

Cl CO2Et

ppm (f1)050100150

171.

704

142.

086

141.

659

129.

071

128.

326

127.

830

127.

261

126.

799

121.

559

120.

418

114.

482

77.3

8777

.070

76.7

51

60.6

81

55.9

14

43.0

01

24.9

50

14.1

10

NH

3Al

Cl CO2Et


S24

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.30

07.

290

7.28

67.

278

7.26

97.

263

7.26

07.

255

7.14

87.

142

7.13

77.

129

7.12

57.

019

7.00

06.

994

6.53

06.

509

5.29

1

4.91

24.

902

4.41

1

3.22

73.

215

3.20

33.

191

3.17

92.

967

2.94

22.

925

2.90

02.

861

2.84

92.

820

2.80

72.

023

3.422.011.87

1.00

1.03

0.93

1.02

2.14

3.06

NH

3Am

ClO

ppm (f1)050100150200

207.

969

142.

139

141.

236

129.

015

128.

510

127.

904

127.

191

126.

585

121.

782

120.

500

114.

762

77.4

8877

.066

76.6

43

56.0

61

50.3

06

29.7

4629

.684

29.3

4425

.487

NH

3Am

ClO


S25

ppm (f1)1.02.03.04.05.06.07.08.0

7.31

57.

309

7.29

17.

276

7.19

17.

186

7.17

2

7.03

67.

029

7.02

47.

012

6.99

36.

814

6.79

56.

546

6.53

46.

523

5.04

15.

031

4.46

44.

438

4.42

24.

401

4.36

03.

667

3.65

53.

644

3.63

43.

622

3.01

22.

990

2.97

02.

947

2.87

82.

865

2.83

62.

823

4.751.98

1.73

1.00

2.62

1.02

3.12

1.00

1.051.15

NH

3An

ClO

OPh

ppm (f1)050100150200

205.

984

157.

592

142.

086

140.

982

129.

684

129.

003

128.

689

128.

112

127.

271

126.

589

122.

002

121.

864

120.

292

114.

928

114.

630

77.3

9777

.080

76.7

63

73.0

76

55.8

17

46.3

76

25.4

45

NH

3An

ClO

OPh


S26

ppm (f1)0.05.010.0

7.94

47.

927

7.92

07.

915

7.60

57.

599

7.58

57.

581

7.57

77.

524

7.50

37.

498

7.47

57.

471

7.26

17.

191

7.18

77.

174

7.16

87.

161

7.15

47.

148

7.14

27.

133

7.12

97.

123

7.11

37.

069

7.06

37.

034

7.02

66.

855

6.85

06.

837

6.83

06.

824

6.57

96.

551

5.02

95.

019

5.00

9

4.49

74.

495

4.48

7

4.19

04.

176

4.16

74.

153

4.13

93.

134

3.07

73.

040

2.80

92.

796

1.75

1.071.82

2.671.861.831.00

1.01

0.99

1.22

1.43

1.28

NH

3Ao

ClO

Ph

ppm (f1)050100150200

199.

092

142.

026

140.

895

136.

904

133.

233

129.

197

128.

952

128.

623

128.

574

128.

521

128.

322

128.

172

128.

049

127.

861

127.

431

127.

214

126.

650

121.

808

121.

244

114.

483

77.3

9177

.073

76.7

56

56.9

40

44.4

74

29.7

3124

.950

NH

3Ao

ClO

Ph


S27

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.30

57.

301

7.29

37.

289

7.28

27.

277

7.26

97.

264

7.15

07.

140

7.13

07.

122

7.11

76.

477

6.45

7

5.28

8

4.89

1

4.47

6

3.20

63.

194

3.18

23.

170

3.15

82.

951

2.92

62.

910

2.88

52.

833

2.82

12.

792

2.77

9

2.02

8

2.993.77

1.00

1.08

1.01

1.00

1.101.14

3.07

NH

3Dm

BrO

ppm (f1)050100150200

207.

888

142.

614

141.

216

131.

915

130.

077

128.

558

127.

965

126.

634

121.

077

115.

232

108.

890

77.3

9977

.080

76.7

65

56.0

53

50.2

84

29.7

7325

.444

NH

3Dm

BrO


S28

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.30

07.

287

7.27

07.

265

7.25

27.

247

7.21

57.

208

7.16

87.

160

7.14

27.

137

6.53

36.

184

5.83

8

4.83

64.

823

4.17

4

3.21

53.

200

3.19

63.

183

3.17

13.

166

3.15

22.

902

2.87

22.

848

2.81

52.

794

2.75

8

2.16

2

2.02

9

3.211.93

1.00

0.96

2.02

1.03

0.94

1.02

2.05

2.98

NH

3Km

OO

O

ppm (f1)050100150200

207.

959

149.

023

146.

291

141.

097

139.

384

137.

568

128.

091

127.

939

127.

219

126.

096

110.

169

108.

484

99.9

3595

.611

76.9

3476

.509

76.0

87

55.8

0150

.502

29.1

4025

.271

NH

3Km

OO

O


S29

ppm (f1)1.02.03.04.05.06.07.0

7.23

77.

069

7.04

97.

003

6.99

06.

983

6.97

36.

967

6.48

96.

484

6.46

6

5.26

6

4.84

44.

834

4.40

5

3.17

53.

163

3.15

13.

139

3.12

72.

928

2.90

32.

887

2.86

2

2.80

32.

790

2.76

12.

749

2.28

8

2.23

62.

073

2.02

1

1.96

9

2.114.03

1.00

1.02

0.94

1.02

1.111.09

3.05

3.00

NH

3Ap

ClO

CH3

ppm (f1)050100150200

208.

087

142.

243

138.

259

137.

637

129.

230

129.

057

127.

207

126.

512

121.

775

120.

612

114.

787

77.4

2077

.102

76.7

84

55.8

96

50.4

36

29.8

1925

.516

21.0

88

NH

3Ap

ClO

CH3


S30

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.58

27.

579

7.56

17.

525

7.50

57.

463

7.44

57.

426

7.37

87.

360

7.34

27.

259

7.21

97.

198

7.05

07.

034

7.02

86.

542

6.53

46.

527

6.52

05.

286

4.93

94.

930

4.49

8

3.23

23.

221

3.20

93.

196

3.18

42.

997

2.97

12.

955

2.93

0

2.86

32.

851

2.82

12.

809

2.08

6

2.102.021.990.912.021.79

1.00

1.04

1.01

1.01

1.051.06

3.00

NH

3Aq

ClO

Ph

ppm (f1)050100150200

207.

932

142.

186

140.

677

140.

369

140.

341

129.

134

128.

856

127.

686

127.

482

127.

318

127.

174

126.

985

126.

887

121.

900

120.

591

114.

883

77.4

6277

.144

76.8

27

55.8

3750

.378

29.8

0925

.561

NH

3Aq

ClO

Ph


S31

ppm (f1)0.01.02.03.04.05.06.07.0

7.26

47.

247

7.21

97.

076

7.04

87.

017

7.01

07.

002

6.53

06.

516

6.50

0

4.89

24.

880

4.45

5

3.20

13.

187

3.18

13.

168

3.15

73.

151

3.13

72.

925

2.89

42.

869

2.85

02.

838

2.83

22.

794

2.06

42.

024

2.02

01.

973

1.973.94

1.01

1.00

0.96

0.98

2.02

2.90

NH

3Ar

ClO

Cl

ppm (f1)050100150200

207.

699

141.

836

139.

836

133.

676

129.

128

128.

660

128.

578

128.

112

127.

401

122.

078

120.

314

114.

872

77.5

0877

.084

76.6

62

55.4

2150

.173

29.7

8925

.365

NH

3Ar

ClO

Cl


S32

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.56

07.

532

7.26

07.

232

7.04

77.

037

7.02

66.

568

6.55

66.

551

6.53

8

5.00

04.

986

3.26

13.

247

3.24

13.

228

3.21

63.

209

3.19

52.

907

2.87

02.

852

2.83

72.

168

2.12

0

1.81

2.18

1.97

1.00

1.01

1.04

2.01

3.01NH

3As

ClO

CN

ppm (f1)050100150200

207.

176

146.

692

141.

428

132.

228

129.

240

127.

698

127.

644

124.

598

122.

491

120.

053

119.

956

118.

485

114.

970

111.

755

77.4

6577

.245

77.0

4276

.956

76.6

16

55.5

71

49.9

6949

.857

29.6

9625

.248

25.1

2725

.084

NH

3As

ClO

CN


S33

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.77

17.

576

7.55

17.

525

7.49

87.

467

7.44

37.

417

7.37

87.

355

7.33

1

7.26

47.

218

7.18

67.

158

6.51

06.

483

5.29

7

4.95

1

4.50

2

3.25

03.

234

3.21

73.

201

3.18

63.

022

2.98

92.

967

2.93

32.

879

2.86

32.

824

2.80

82.

263

2.09

77.07

3.89

1.00

0.99

1.00

0.97

2.06

3.06

NH

3Dq

BrO

Ph

ppm (f1)050100150200

207.

921

142.

583

140.

726

140.

366

140.

239

131.

996

130.

164

128.

966

128.

844

127.

475

127.

352

127.

163

126.

999

121.

094

115.

293

108.

975

77.5

2877

.104

76.6

80

55.7

7650

.299

29.8

3325

.421

NH

3Dq

BrO

Ph


S34

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.35

27.

323

7.31

47.

286

7.28

37.

262

7.23

37.

209

7.20

07.

184

7.17

77.

158

7.00

06.

976

6.95

26.

876

6.84

7

6.63

56.

610

6.55

76.

531

6.50

44.

538

4.52

64.

505

4.49

34.

297

4.27

64.

260

4.23

93.

981

3.79

53.

757

2.26

02.

252

2.22

92.

217

2.20

92.

196

2.15

72.

114

7.58

1.132.12

1.112.01

1.00

1.07

0.96

3.10

2.17

NH3Lb OMe

ppm (f1)50100150

159.

117

145.

403

136.

003

129.

666

128.

691

128.

519

128.

252

127.

713

127.

195

126.

453

124.

703

117.

513

114.

242

113.

983

77.5

0077

.077

76.6

51

56.6

3655

.292

45.0

0442

.131

NH3Lb OMe


S35

ppm (f1)0.05.0

7.34

37.

331

7.32

17.

314

7.29

57.

254

7.25

17.

236

7.22

67.

221

7.21

77.

200

6.94

36.

939

6.92

26.

917

6.88

66.

864

6.84

0

6.58

86.

585

6.46

66.

445

5.26

74.

524

4.51

64.

496

4.48

94.

242

4.22

84.

212

4.19

84.

011

3.78

43.

769

2.25

32.

245

2.23

92.

231

2.22

02.

213

2.20

62.

199

2.19

12.

162

2.15

22.

133

2.10

1

4.053.24

1.002.03

0.920.99

0.98

1.031.003.09

2.21NH

3Mb OMe

Cl

ppm (f1)050100150

159.

249

144.

473

144.

043

135.

565

129.

206

128.

750

128.

602

128.

420

127.

708

127.

120

126.

798

126.

320

121.

957

115.

326

114.

068

113.

960

77.3

8977

.072

76.7

54

56.6

35

55.3

51

44.9

4141

.674

NH

3Mb OMe

Cl


S36

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.49

27.

464

7.44

57.

427

7.39

87.

183

7.15

5

7.09

67.

089

7.06

67.

047

7.04

26.

963

6.93

46.

673

6.64

66.

618

6.59

3

4.60

14.

592

4.56

54.

556

4.34

84.

329

4.30

94.

289

4.07

53.

848

2.27

62.

266

2.25

62.

248

2.21

02.

171

2.072.07

2.031.182.14

3.20

1.00

1.08

1.00

3.31

2.27

NH

3Nb OMe

Br

ppm (f1)050100150

159.

250

145.

513

144.

589

135.

811

131.

702

130.

518

130.

111

129.

614

128.

753

127.

782

127.

508

124.

060

120.

231

117.

680

114.

458

114.

101

77.6

0177

.177

76.7

53

56.5

83

55.3

88

44.5

3542

.137

NH

3Nb OMe

Br


S37

ppm (f1)0.01.02.03.04.05.06.07.08.0

7.41

87.

389

7.26

57.

240

7.10

07.

074

7.05

0

6.98

26.

953

6.79

76.

772

6.74

76.

576

6.54

9

4.50

44.

496

4.46

64.

458

3.97

73.

873

3.21

03.

189

3.16

93.

149

2.17

32.

164

2.15

62.

146

2.13

02.

121

2.11

32.

104

1.87

31.

833

1.79

21.

752

1.43

51.

413

1.35

12.081.051.091.991.01

0.95

1.00

0.943.07

0.97

1.03

1.05

3.14

NH

CH3

3Ob OMe

ppm (f1)050100150

159.

094

144.

887

136.

668

128.

964

127.

761

126.

945

126.

901

126.

038

117.

493

114.

114

114.

010

77.5

4677

.123

76.6

99

56.3

9855

.367

41.7

0938

.307

31.3

57

20.1

79

NH

CH3

3Ob OMe


S38

ppm (f1)0.05.010.0

7.60

07.

596

7.57

97.

563

7.53

97.

518

7.45

97.

454

7.44

07.

421

7.36

47.

346

7.34

07.

338

7.33

47.

319

7.30

17.

271

7.25

87.

235

7.22

97.

222

7.21

8

7.04

47.

025

7.00

76.

664

6.64

56.

611

6.59

96.

591

6.58

06.

562

4.68

54.

678

4.65

84.

651

4.35

84.

344

4.32

84.

314

4.11

32.

355

2.34

82.

341

2.33

02.

322

2.31

62.

308

2.30

22.

272

2.26

52.

244

2.21

2

4.462.122.309.551.05

3.04

1.00

1.070.92

2.32NH

Ph3Lf

ppm (f1)50100150

145.

335

145.

295

142.

980

140.

809

140.

727

129.

719

128.

814

128.

729

128.

568

127.

415

127.

333

127.

286

127.

186

127.

098

126.

534

124.

775

117.

683

114.

341

77.3

8077

.063

76.7

45

57.0

04

44.9

7742

.100

NH

Ph3Lf


S39

ppm (f1)1.02.03.04.05.06.07.08.09.0

7.57

47.

554

7.52

77.

506

7.48

27.

462

7.43

67.

417

7.39

87.

343

7.32

67.

307

7.28

87.

247

7.23

07.

220

7.20

06.

958

6.95

36.

937

6.93

26.

608

6.47

96.

458

5.23

74.

599

4.59

34.

571

4.56

54.

256

4.24

24.

226

4.21

24.

051

2.30

12.

294

2.28

82.

275

2.26

82.

262

2.25

62.

235

2.20

62.

176

4.232.052.183.273.21

0.98

0.941.00

1.00

1.000.98

2.18

NH

Ph3Mf

Cl

ppm (f1)050100150

144.

376

143.

948

142.

559

140.

884

140.

740

129.

263

128.

875

128.

811

128.

643

127.

611

127.

488

127.

433

127.

218

127.

120

127.

068

126.

885

126.

379

122.

144

115.

468

77.4

3077

.112

76.7

94

56.9

68

44.9

0141

.656

NH

Ph3Mf

Cl


S40

ppm (f1)0.05.010.0

7.43

07.

424

7.40

27.

399

7.36

57.

360

7.35

47.

337

7.33

17.

308

7.30

37.

294

7.28

87.

283

7.27

17.

251

7.24

67.

236

7.22

77.

219

7.21

47.

201

7.19

87.

192

6.95

06.

942

6.92

26.

914

6.59

86.

593

6.59

06.

471

6.44

34.

570

4.56

04.

534

4.52

4

4.25

34.

234

4.21

34.

194

4.03

52.

281

2.27

22.

262

2.24

82.

237

2.22

92.

216

2.17

62.

138

2.09

5

2.288.66

1.00

0.981.01

1.01

1.051.05

2.22

NH

3Ma

Cl

ppm (f1)050100

143.

843

143.

414

142.

943

128.

668

128.

218

128.

069

127.

918

127.

370

126.

621

126.

294

126.

046

125.

788

121.

499

114.

843

76.9

6876

.544

76.1

19

56.7

02

44.3

4041

.129

NH

3Ma

Cl


S41

ppm (f1)0.05.0

7.49

67.

481

7.47

47.

467

7.45

6

7.36

87.

363

7.35

77.

340

7.33

57.

313

7.29

27.

287

7.28

27.

268

7.23

57.

230

7.22

37.

207

7.20

46.

988

6.98

66.

980

6.97

86.

960

6.95

76.

952

6.94

96.

612

6.60

86.

604

6.60

06.

530

6.50

25.

309

4.58

14.

572

4.54

44.

535

4.27

94.

260

4.23

94.

220

4.04

32.

282

2.27

32.

264

2.24

82.

238

2.23

02.

220

2.19

42.

157

2.15

42.

116

2.11

02.

073

1.757.55

0.90

0.880.89

1.00

1.040.98

2.24NH

3Mu

Cl

Br

ppm (f1)050100

144.

154

143.

662

142.

503

131.

826

129.

231

128.

790

128.

554

128.

305

127.

211

126.

903

126.

296

122.

377

121.

543

115.

512

77.3

5577

.038

76.7

21

56.6

94

44.7

4241

.641

NH

3Mu

Cl

Br


S42

HPLC spectra of 3Aa:


S43

HPLC spectra of 3Ab:


S44

HPLC spectra of 3Ac:


S45

HPLC spectra of 3Ad:


S46

HPLC spectra of 3Ae:


S47

HPLC spectra of 3Af:


S48

HPLC spectra of 3Ag:


S49

HPLC spectra of 3Ah:


S50

HPLC spectra of 3Ai:


S51

HPLC spectra of 3Aj:


S52

HPLC spectra of 3Bb:


S53

HPLC spectra of 3Cb:


S54

HPLC spectra of 3Db:


S55

HPLC spectra of 3Eb:


S56

HPLC spectra of 3Fb:


S57

HPLC spectra of 3Gb:


S58

HPLC spectra of 3Hb:


S59

HPLC spectra of 3Ib:


S60

HPLC spectra of 3Jb:


S61

HPLC spectra of 3Kb:


S62

HPLC spectra of 3Ak:


S63

HPLC spectra of 3Al:


S64

HPLC spectra of 3Am:


S65

HPLC spectra of 3An:


S66

HPLC spectra of 3Ao:


S67

HPLC spectra of 3Dm:


S68

HPLC spectra of 3Km:


S69

HPLC spectra of 3Ap:


S70

HPLC spectra of 3Aq:


S71

HPLC spectra of 3Ar:


S72

HPLC spectra of 3As:


S73

HPLC spectra of 3Dq:


S74

HPLC spectra of 3Lb:


S75

HPLC spectra of 3Mb:


S76

HPLC spectra of 3Nb:


S77

HPLC spectra of 3Ob:


S78

HPLC spectra of 3Lf:


S79

HPLC spectra of 3Mf:


S80

HPLC spectra of 3Ma:


S81

HPLC spectra of 3Mu:


S82


highly regio-, diastereo- and enantioselective one-pot ... · s3 table s2. optimization of the...

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