Metal-free Aerobic C-H Oxidation of Cyclic Enones · 2014-06-16 · 1 Metal-free Aerobic C-H...

1

Metal-free Aerobic C-H Oxidation of Cyclic Enones

P. A. Peixoto, M. Cormier, J. Ekosso Epane, A. Jean, J. Maddaluno, M. De Paolis

[email protected]

Table of contents

I) Experimental Section 2

II) Abbreviations 14

III) 1H and 13C NMR Spectra 15

Electronic Supplementary Material (ESI) for Organic Chemistry Frontiers.This journal is © the Partner Organisations 2014

2

I) Experimental Section

All reactions were carried out under a nitrogen or argon atmosphere with dry solvents

under anhydrous conditions, unless otherwise noted. Dry tetrahydrofuran (THF), diethyl ether

(Et2O), methylene chloride (CH2Cl2), and toluene were obtained by distillation (from CaH2

for CH2Cl2, sodium/benzophenone for THF, from sodium for toluene and, from sodium

benzophenone for Et2O). Methanol (MeOH), N,N'-dimethylformamide (DMF) and

dimethylsulfoxide (DMSO) were purchased in anhydrous form and used without further

purification. Ethyl acetate (EtOAc), diethyl ether (Et2O), methylene chloride (CH2Cl2), and

cyclohexane were purchased at ACS grade quality and used without further purification,

unless otherwise stated. Reagents were purchased at the highest commercial quality and used

without further purification, unless otherwise stated. Yields refer to chromatographically and

spectroscopically (1H NMR and 13C NMR) homogeneous materials, unless otherwise stated.

Reactions were monitored by thin-layer chromatography (TLC) carried out on Merck silica

gel plates with QF-254 indicator and an ethanolic solution of ammonium molybdate or

potassium permanganate and heat as developing agents. Merck silica gel (60, particle size

0.040-0.063 mm) was used for flash column chromatography. NMR spectra were recorded on

Bruker Advance DMX -300 or -200 instruments and calibrated using residual undeuterated

solvent as an internal reference (7.26 ppm and 77.00 ppm for 1H and 13C NMR in CDCl3; 7.16

ppm and 128.06 ppm for 1H and 13C NMR in C6D6). The following abbreviations were used

to describe the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet,

m = multiplet, pent = pentet, hex = hexet, br = broad. IR spectra were recorded on a

PerkinElmer Spectrum 100 FT-IR-spectrometer with only major peaks being reported. High-

resolution mass spectra (HRMS) were recorded on an LCT Premier XE benchtop orthogonal

acceleration time-of-flight (TOF) mass spectrometer (Waters Micromass).

3

Synthesis of mesylates 1a-h:

DOO

R

A

OO

O

9O

R

O

R OMS

1

RCHO (3.0 eq)

Hantzsch ester (1.0 eq)rac-proline (5 mol%)CH2Cl2, rt, 24 h

EVK (1.5 eq)Et3N (2.0 eq)EtOAcrt, 48 h

PTSA (10 mol%)Toluene, 110°C

2 h

1- NaBH4 (0.4 eq), MeOH,-40oC to -20oC, 1 h

2- MsCl (1.5 eq), Et3N (3 eq),CH2Cl2, 0°C to rt, 30 min

then

● General procedure A for the synthesis of known alkylated cyclopentanediones:

The alkylated cyclopentanediones were prepared according to a slightly modified procedure

from Ramachary:1 To a stirred solution of cyclopentanedione (1.0 eq), aldehyde (3.0 eq) and

Hantzsch ester (1.0 eq) in CH2Cl2 (0.3 M) at rt was added proline (5 mol%). The resulting

mixture was stirred for 24 h before being concentrated in vacuo. The crude reaction mixture

was then triturated with a mixture of EtOAc/Et2O (1/4). The resulting suspension was filtered,

washed with Et2O and dried in vacuo to afford the desired pure alkyl cyclopentadione.

Aa:1 According to the general procedure A, the reaction of 1,3-cyclopentanedione (200 mg,

2.0 mmol), benzaldehyde (620µL, 6.0 mmol), Hantzsch ester (517 mg, 2.0 mmol) and proline

(12 mg, 0.1 mmol) in CH2Cl2 (6.7 mL) provided Aa (310 mg, 81%) as a white powder.

1 D. B. Ramachary and M. Kishor, Org. Biomol. Chem., 2008, 6, 4176.

DOO

4

Ab:1 According to the general procedure A, the reaction of 1,3-cyclopentanedione (1.2 g,

12.20 mmol), 2-naphtaldehyde (5.73 g, 36.60 mmol), Hantzsch ester (3.1 g, 12.20 mmol) and

proline (70 mg, 0.61 mmol) in CH2Cl2 (41 mL) provided Ab (2.57 mg, 88%) as a white

powder.

Ac:2 According to the general procedure A, the reaction of 1,3-cyclopentanedione (589 mg,

6.0 mmol), anisaldehyde (2.19 mL, 18.0 mmol), Hantzsch ester (1.520 g, 6.0 mmol) and

proline (36 mg, 0.3 mmol) in CH2Cl2 (20 mL) provided Ac (1.12 g, 85%) as a white powder .

IR (film) νmax 2909, 1563, 1509, 1433, 1355, 1324, 1260, 1242, 1178, 1030, 815, 665 cm-1; 1H NMR (300 MHz, CDCl3 + 2 drops of MeOD) δ 7.08 (d, J = 8.4 Hz, 2H), 6.68 (d, J = 8.5

Hz, 2H), 3.66 (s, 3H), 3.32 (s, 2H), 2.38 (s, 4H); 13C NMR (75 MHz, CDCl3) δ 157.5, 132.2,

129.2 (2C), 117.5, 113.4 (2C), 55.0, 30.2 (2C), 25.7.

Ad:2 According to the general procedure A, the reaction of 1,3-cyclopentanedione (589 mg,

6.0 mmol), o-bromobenzaldehyde (2.10 mL, 18 mmol), Hantzsch ester (1.52 g, 6.0 mmol) and

proline (36 mg, 0.3 mmol) in CH2Cl2 (20 mL) provided Ad (1.24 g, 89%). IR (film) νmax

2922, 1568, 1383, 1267, 1035, 744, 659 cm-1; 1H NMR (300 MHz, CDCl3+ 2 drops of

MeOD) δ 7.42 (d, J = 7.7 Hz, 1H), 7.04-7.17 (m, 1H), 6.83-7.02 (m, 2H), 3.49 (s, 2H), 2.45

(s, 4H); 13C NMR (75 MHz, CDCl3) δ 197.2, 138.2, 132.2, 129.2, 127.3, 127.0, 124.4, 114.9,

30.3 (2C), 27.2.

2 K. Sudheendran, C. C. Malakar, J. Conrad, and U. Beifuss, J. Org. Chem., 2012, 77, 10194.

DOO

DOO

OMe

DOO

Br

5

Ae:1 According to the general procedure A, the reaction of 1,3-cyclopentanedione (589 mg,

6.0 mmol), o-nitrobenzaldehyde (2.72 g, 18 mmol), Hantzsch ester (1.52 g, 6.0 mmol) and

proline (36 mg, 0.3 mmol) in CH2Cl2 (20 mL) provided Ae (1.38 g, 77%). 1H NMR (300

MHz, CDCl3+ 2 drops of MeOD) δ 7.68 (d, J = 8.1 Hz, 1H), 7.30 (m, 1H), 7.06-7.19 (m, 2H),

3.63 (s, 2H), 2.36 (s, 4H); 13C NMR (75 MHz, CDCl3) δ 149.1, 134.1, 132.5, 130.7, 126.5,

124.0, 114.4, 30.0 (2C), 23.3.

Af: Triketone Af was synthesized according to known procedures.3,4,5,6

Ag:1 According to the general procedure A, the reaction of 1,3-cyclopentanedione (980 mg,

10.0 mmol), heptanaldehyde (4.20 mL, 30.0 mmol), Hantzsch ester (2.53 g, 10.0 mmol) and

proline (36 mg, 0.5 mmol) in CH2Cl2 (33 mL) provided Ag (1.37 g, 70%).

● General procedure B for the synthesis of enones:

To a stirred solution of alkylated cyclopentanedione (1.0 eq) and Et3N (2.0 eq) in

EtOAc (0.2 M) at rt was added EVK (1.5 eq). The resulting mixture was stirred for 2 days

3 P. K. Ruprah, J.-P. Cros, J. E. Pease, W. G. Whittingham and J. M. Williams, Eur. J. Org. Chem. 2002, 3145.4 E. Lacoste, E. Vaique, M. Berlande, I. Pianet, J. M. Vincent and Y. Landais, Eur. J. Org. Chem. 2007, 167.5 X.-M. Zhang, M. Wang, Y.-Q. Tu, C.-A. Fan, Y.-J. Jiang, S.-Y. Zhang and F.-M. Zhang, Synlett 2008, 2831.6 J. Xu, L. Trzoss, W. K. Chang and E. A. Theodorakis, Angew. Chem. Int. Ed. 2011, 50, 3672.

DOO

O2N

DOO

OO

6

before being concentrated in vacuo. When required, flash column chromatography of the

crude was performed to afford the triketone. Otherwise, the next step was directly carried out.

To a stirred solution of triketone (1 eq) in toluene (0.1 M) at rt was added PTSA (10% mol).

The resulting mixture was refluxed for 2 h before being cooled to rt and quenched with

NaHCO3 (sat. aq.). The resulting mixture was diluted with EtOAc, the layers were separated

and the aqueous layer was back extracted with EtOAc. The combined organic layers were

washed with brine, dried (Na2SO4) and concentrated in vacuo. Flash column chromatography

(silica gel) of the crude afforded enones 9a-i.

7

9a: According to the general procedure B, the reaction of alkylated cyclopentanedione Aa

(305 mg, 1.62 mmol), triethylamine (0.45 mL, 3.24 mmol), EVK (0.32 mL, 3.24 mmol) in

EtOAc (8.1 mL) gave triketone Ba (9.12 g, 93%) as a colorless oil (silica gel - cyclohexane:

EtOAc, 75:25). Rf = 0.35 (silica gel, cyclohexane: EtOAc, 75:25). The reaction of the

corresponding triketone (364 mg, 1.34 mmol), PTSA (26 mg, 0.13 mmol) in toluene (13.4

mL) provided enone 9a (300 mg, 88%) as colorless oil (silica gel - cyclohexane: EtOAc,

65:35). Rf = 0.45 (silica gel, cyclohexane: EtOAc, 65:35); IR (film) ν 2926, 1730, 1664,

1450, 1311, 1114, 748, 705, cm-1; 1H NMR (300 MHz, CDCl3) δ 7.22-7.31 (m, 3H), 6.98-

7.08 (m, 2H), 3.05 (d, J = 13.0 Hz, 1H), 2.98 (d, J = 13.0 Hz, 1H), 2.41-2.75 (m, 3H), 2.13-

2.40 (m, 3H), 1.97 (ddt, J = 17.7, 9.9, 1.6 Hz, 1H), 1.82 (ddd~dt, J = 13.7, 6.1 Hz, 1H), 1.81

(s, 3H); 13C NMR (75 MHz, CDCl3) δ 218.4, 197.6, 162.0, 135.7, 131.0, 129.5 (2C), 128.5

(2C), 127.3, 54.2, 42.8, 36.6, 32.6, 28.4, 25.6, 10.9; HRMS (EI): calcd for C17H18O2+ [M+]:

254.1307, found 254.1324.

9b: According to the general procedure B, the reaction of alkylated cyclopentanedione Ab

(2.57 g, 10.8 mmol), triethylamine (3.0 mL, 21.6 mmol), EVK (2.15 mL, 21.6 mmol) in

EtOAc (54 mL) provided triketone Bb (2.85 g, 82%) as colorless oil (silica gel - cyclohexane:

EtOAc, 75:25). Rf = 0.40 (silica gel, cyclohexane: EtOAc, 75:25). The reaction of the

corresponding triketone (2.85 g, 8.8 mmol), PTSA (170 mg, 0.88 mmol) in toluene (88 mL)

provided enone 9b (2.59 g, 96%) as colorless oil (silica gel - cyclohexane: EtOAc, 80:20). Rf

= 0.40 (silica gel, cyclohexane: EtOAc, 75:25); IR (film) ν 2926, 2857, 1735, 1644, 1501,

1350, 1138, 962, 825, 752, 480 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.63-7.84 (m, 3H), 7.33-

7.55 (m, 3H), 7.12 (d, J = 8.4 Hz, 1H), 3.20 (d, J = 12.9 Hz, 1H), 3.11 (d, J = 12.9 Hz, 1H),

2.42-2.76 (m, 3H), 2.07-2.29 (m, 3H), 1.71 – 1.93 (m, 2H), 1.81 (s, 3H); 13C NMR (75 MHz,

O

O

O

O

8

CDCl3) δ 218.5, 197.5, 162.1, 133.3, 133.1, 132.3, 131.0, 128.2, 128.0, 127.5 (2C), 126.3,

125.9, 54.3, 42.9, 36.6, 32.6, 28.6, 26.8, 25.7, 10.8; HRMS (EI): calcd for C21H20O2+ [M+]:

304.1463, found 304.1456.

9

9c: According to the general procedure B, the reaction of alkylated cyclopentanedione Ac

(1.12 g, 5.1 mmol), triethylamine (1.43 mL, 10.2 mmol), EVK (0.76 mL, 7.7 mmol) in EtOAc

(25.5 mL) provided triketone Bc (1.53 g, 99%) as colorless oil (silica gel chromatography -

cyclohexane: EtOAc, 75:25). Rf = 0.30 (silica gel, cyclohexane: EtOAc, 75:25). The reaction

of the corresponding triketone (261 g, 0.86 mmol), PTSA (17 mg, 0.09 mmol) in toluene (8.6

mL) provided enone 9c (244 mg, 99%) as colorless oil (silica gel - cyclohexane: EtOAc,

75:25). Rf = 0.3 (silica gel, cyclohexane: EtOAc, 75:25); IR (film) ν 2926, 2845, 1730, 1659,

1607, 1513, 1446, 1300, 1251, 1110, 1031, 964, 835, 746, 492 cm-1; 1H NMR (300 MHz,

CDCl3) δ 6.85 (d, J = 8.6 Hz, 2H), 6.69 (d, J = 8.6 Hz, 2H), 3.67 (s, 3H), 2.90 (d, J = 13.2 Hz,

1H), 2.82 (d, J = 13.2 Hz, 1H), 2.42 – 2.67 (m, 2H), 2.34 (dd, J = 18.4, 4.6 Hz, 1H), 2.12 –

2.22 (m, 2H), 1.87 – 2.11 (m, 2H), 1.71 (s, 3H), 1.68 (ddd~dt, J = 13.8, 6.0 Hz, 1H); 13C

NMR (75 MHz, CDCl3) δ 218.2, 197.3, 162.1, 158.5, 130.5, 130.3, 127.3, 113.5, 54.9, 54.0,

41.7, 36.3, 32.3, 27.9, 25.3, 10.6; HRMS (ESI): calcd for C18H21O3 [M+H]+: 285.1491, found

285.1476.

9d: According to the general procedure B, the reaction of alkylated cyclopentanedione Ad


EtOAc (7.6 mL) provided triketone Bd (348 mg, 65%) as colorless oil (silica gel -

cyclohexane: EtOAc, 75:25). Rf = 0.35 (silica gel, cyclohexane: EtOAc, 75:25). The reaction

of the corresponding triketone (980 mg, 2.80 mmol), PTSA (54 mg, 0.28 mmol) in toluene

(28 mL) provided enone 9d (926 mg, 99%) as colorless oil (silica gel - cyclohexane: EtOAc,

75:25). Rf = 0.3 (silica gel, cyclohexane: EtOAc, 75:25); IR (film) ν 2921, 2848, 1738, 1662,

1653, 1439, 1348, 1115, 1024, 753, 573, 448 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.43 (d, J

= 7.9 Hz, 1H), 7.15 (t, J = 6.8 Hz, 1H), 6.97 – 7.08 (m, 2H), 3.45 (d, J = 13.3 Hz, 1H), 2.92

(d, J = 13.3 Hz, 1H), 2.51 – 2.73 (m, 2H), 2.39 (ddd, J = 18.4, 5.6, 1.5 Hz, 1H), 2.11 – 2.31

O

MeO

O

O

Br

O

10

(m, 3H), 1.85 – 2.03 (m, 1H), 1.72 (ddd~dt, J = 13.9, 5.7 Hz, 1H), 1.70 (s, 3H); 13C NMR (75

MHz, CDCl3) δ 218.0, 197.2, 160.3, 135.5, 133.0, 131.7, 131.4, 128.8, 127.3, 125.2, 53.6,

40.4, 36.8, 32.5, 28.5, 25.5, 10.8; MS (EI): 332 and 334; HRMS (EI): calcd for C17H17O2Br+

[M+]: 332.0412, found 332.0407.

9e: According to the general procedure B, the reaction of alkylated cyclopentanedione Ae

(1.24 g, 5.33 mmol), triethylamine (1.49 mL, 10.70 mmol), EVK (0.80 mL, 8.00 mmol) in

EtOAc (26.7 mL) provided triketone Be (1.45 g, 66%) as colorless oil (Silica gel

chromatography - cyclohexane: EtOAc, 65:35). Rf = 0.65 (silica gel, cyclohexane: EtOAc,

5:5). The reaction of the corresponding triketone (1.45 g, 4.60 mmol), PTSA (88 mg, 0.46

mmol) in toluene (46 mL) provided enone 9e (1.11 g, 76%) as a colorless oil (silica gel -

cyclohexane: EtOAc / 75:25). Rf = 0.55 (silica gel, cyclohexane: EtOAc, 5:5); IR (film) ν

2926, 2865, 1737, 1660, 1522, 1446, 1358, 1288, 1132, 1110, 959, 852, 786, 715, 495 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.99 (dd, J = 8.0, 1.5 Hz, 1H), 7.63 (td, J = 7.4, 1.5 Hz, 1H),

7.51 (td, J = 8.0, 1.5 Hz, 1H), 7.34 (dd, J = 7.4, 1.5 Hz, 1H), 3.93 (d, J = 13.5 Hz, 1H), 3.18

(d, J = 13.5 Hz, 1H), 2.78 – 3.01 (m, 1H), 2.26 – 2.73 (m, 5H), 2.18 (ddd, J = 13.9, 4.8, 2.3

Hz, 1H), 1.84 (s, J = 1.0 Hz, 3H), 1.68 – 1.89 (ddd~dt, J = 13.7, 6.8 Hz, 1H); 13C NMR (75

MHz, CDCl3) δ 217.2, 196.8, 160.2, 149.3, 133.2, 133.0, 131.9, 130.8, 128.6, 125.4, 52.9,

36.6 (2C), 32.3, 27.3, 25.3, 11.0; HRMS (EI): calcd for C17H17NO4+ [M+]: 299.1158, found

299.1162.

9f: To a stirred solution of 2-allylcyclopentane-1,3-dione (853mg, 6.2 mmol) and EVK (1.23

mL, 12.4 mmol) in H2O (12.4 mL) at rt was added AcOH (180 µL, 3.1 mmol). The resulting

mixture was refluxed for 4 h before being cooled down to rt and extracted with EtOAc (3 x 25

O

NO2

O

O

O

11

mL). The combined organic layers were then washed with NaHCO3 (2 x 20 mL, sat. aq.),

dried (Na2SO4) and concentrated in vacuo. Purification (silica gel, cyclohexane:EtOAc from

90:10 to 70:30) afforded triketone Bf (1.03 g, 75%) as colorless oil. Rf = 0.20 (silica gel,

cyclohexane: EtOAc, 8:2). The reaction of the corresponding triketone (810 mg, 3.6 mmol),

PTSA (69 mg, 0.36 mmol) in toluene (36 mL) provided enone 9f (661 mg, 90%) as a

colorless oil (silica gel - cyclohexane: EtOAc / 75:25). Rf = 0.25 (silica gel, cyclohexane:

EtOAc, 8:2); IR (film) ν 2949, 2921, 2870, 1739, 1649, 1436, 1354, 1316, 1160, 1113, 968,

921, 577, 491 cm-1; 1H NMR (300 MHz, CDCl3) δ 5.55 – 5.75 (m, 1H), 4.97 – 5.14 (m, 2H),

2.25 – 2.93 (m, 8H), 2.12 (ddd, J = 13.6, 5.4, 1.8 Hz, 1H), 1.72 (s, 3H), 1.69 (ddd~dt, J =

13.9, 5.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 216.4, 197.6, 161.7, 131.9, 130.3, 119.2,

52.5, 39.2, 35.6, 32.1, 26.4, 24.7, 10.6; HRMS (EI): calcd for C13H16O2+ [M+]: 204.1150,

found 204.1142.

9g: According to the general procedure B, the reaction of alkylated cyclopentanedione Ag


EtOAc (5.3 mL) provided triketone Bg (260 mg, 88%) as a colorless oil (silica gel –

cyclohexane: EtOAc / 65:35). Rf = 0.40 (silica gel, cyclohexane: EtOAc, 75:25). The reaction

of the corresponding triketone (260 mg, 0.93 mmol), PTSA (18 mg, 0.09 mmol) in toluene

(9.3 mL) provided enone 9g (224 mg, 92%) as a colorless oil (silica gel - cyclohexane: EtOAc

/ 75:25). Rf = 0.40 (silica gel, cyclohexane: EtOAc, 75:25); IR (film) ν 2926, 2855, 1740,

1663, 1651, 1457, 1377, 1356, 1154, 1114, 959, 573, 495 cm-1; 1H NMR (300 MHz, CDCl3)

δ 2.44 – 2.87 (m, 3H), 2.14 – 2.41 (m, 3H), 1.97 – 2.13 (m, 1H), 1.62 (s, 3H), 1.40 – 1.68 (m,

3H), 1.10 (s, 10H), 0.71 (t, J = 6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 218.0, 197.2,

160.3, 135.5, 133.0, 131.7, 131.4, 128.8, 127.3, 125.2, 53.6, 40.4, 36.8, 32.5, 28.5, 25.5, 10.8;

HRMS (EI): calcd for C17H26O2+ [M+]: 262.1933, found 262.1939.

O

O

12

9h:7 According to the general procedure C, the reaction of the corresponding triketone (9.09

g, 46.4 mmol), PTSA (890 mg, 4.6 mmol) in toluene (460 mL) provided diketone 9h (8.26 g,

97%) as colorless oil (silica gel chromatography - cyclohexane: EtOAc, 60:40).

● General procedure for the synthesis of mesylates 1a-i:

To a stirred solution of diketone 9a-i (1 eq) in MeOH (0.1M) at -40oC was added

NaBH4 (0.5 eq). The resulting mixture was stirred for 1 h to -20 oC and subsequently

concentrated in vacuo. The crude was diluted with CH2Cl2 and treated with HCl (1N, aq. sol.).

The layers were separated and aqueous layer was re-extracted with CH2Cl2. The combined

organic layers were then washed with brine, dried (Na2SO4) and concentrated in vacuo

leading to the corresponding alcohol as colorless oil which was used directly without further

purification.

To a stirred solution of the crude alcohol and Et3N (3 eq) in CH2Cl2 (0.1 M) at rt was added

methanesulfonyl chloride (1.5 eq). The resulting mixture was stirred for 30 min before it was

quenched with NaHCO3 (sat. aq.). The layers were separated and the aqueous layer was re-

extracted with CH2Cl2. The combined organic layers were dried (Na2SO4) and concentrated in

vacuo. Flash column chromatography (silica gel) of the crude afforded mesylate 1a-i.

1a: According to the general procedure, the reaction of diketone 9a (294 mg, 1.16 mmol),

NaBH4 (22 mg, 0.56 mmol) in MeOH (11.6 mL) provided the crude alcohol.

The reaction of the crude alcohol, Et3N (0.49 mL, 3.48 mmol) and MsCl (0.14 mL, 1.74

mmol) in CH2Cl2 (11.6 mL) provided mesylate 1a (360 mg, 93% over two steps) as a slightly

yellow amorphous powder (silica gel – CH2Cl2: EtOAc, 95:5). Rf = 0.35 (silica gel,

7 S. G. Davies, A. J. Russell, R. L. Sheppard, A. D. Smith and J. E. Thomson, Org. Biomol. Chem. 2007, 5, 3190

O

O

O

OMs

13

cyclohexane: EtOAc, 7:3); IR (film) ν 2927, 1653, 1331, 1173, 940, 843, 703 cm-1; 1H NMR

(300 MHz, CDCl3) δ 6.97 – 7.22 (m, 5H), 4.60 (dd, J = 10.4, 8.2 Hz, 1H), 2.96 (s, 3H), 2.94

(d, J = 13.7 Hz, 1H), 2.83 (d, J = 13.7 Hz, 1H), 2.02 – 2.50 (m, 6H), 1.74 – 1.98 (m, 2H), 1.64

(s, 3H); 13C NMR (75 MHz, CDCl3) δ 196.9, 160.5, 137.1, 131.5, 130.0 (2C), 127.8 (2C),

126.5, 88.1, 48.7, 37.9, 37.5, 32.7, 32.4, 27.2, 26.1, 10.6; HRMS (EI): calcd for C18H22O4S+

[M+]: 334.1239, found 334.1226.

1b: According to the general procedure, the reaction of diketone 9b (2.5 g, 8.21 mmol),

NaBH4 (156 mg, 4.11 mmol) in MeOH (82 mL) provided the crude alcohol.


mmol) in CH2Cl2 (82 mL) provided mesylate 1b (3.0 g, 95% over two steps) as a slightly

yellow amorphous powder (silica gel– CH2Cl2: EtOAc, 95:5). Rf = 0.35 (silica gel,

cyclohexane: EtOAc, 65:35); IR (film) ν 2928, 1656, 1351, 1331, 1174, 941, 846, 754, 734

cm-1; 1H NMR (300 MHz, CDCl3) δ 7.64 – 7.80 (m, 3H), 7.56 (s, 1H), 7.35 – 7.47 (m, 2H),

7.21 (d, J = 8.4 Hz, 1H), 4.66 (dd, J = 13.7, 10.1 Hz, 1H), 3.15 (d, J = 13.7 Hz, 1H), 3.06 (d, J

= 13.7 Hz, 1H), 3.00 (s, 3H), 2.03 – 2.44 (m, 6H), 1.89 (ddd~dt, J = 12.9, 6.9 Hz, 1H), 1.72

(s, 3H), 1.63 – 1.79 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 197.3, 161.1, 135.2, 133.2, 132.2,

132.0, 129.1, 128.6, 127.7, 127.6, 127.5, 126.3, 125.8, 88.5, 49.3, 38.4, 38.0, 33.3, 32.9, 27.8,

26.6, 11.0; HRMS (ESI): calcd for C22H25O4S+ [M + H+]: 385.1474, found 385.1480.

O

OMs

14

1c: According to the general procedure, the reaction of diketone 9c (240 mg, 0.84 mmol),


The reaction of the crude alcohol, Et3N (0.35 mL, 2.52 mmol) and MsCl (98 µL, 1.26 mmol)

in CH2Cl2 (8 mL) provided mesylate 1c (269 mg, 88% over two steps) as a light yellow

amorphous powder (silica gel – CH2Cl2: EtOAc, 9:1). Rf = 0.3 (silica gel, cyclohexane:

EtOAc, 65:35); IR (film) νmax 2921, 2854, 1652, 1512, 1330, 1245, 1172, 1018, 941, 833, 525

cm-1; 1H NMR (300 MHz, CDCl3) δ 6.96 (d, J = 8.6 Hz, 2H), 6.70 (d, J = 8.7 Hz, 2H), 4.61

(dd, J = 10.4, 8.3 Hz, 1H), 3.69 (s, 3H), 3.00 (s, 3H), 2.91 (d, J = 13.8 Hz, 1H), 2.81 (d, J =

13.8 Hz, 1H), 1.98 – 2.39 (m, 6H), 1.84 (ddd~dt, J = 13.0, 6.4 Hz, 1H), 1.68 – 1.80 (m, 1H),

1.66 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 197.1, 160.9, 158.3, 131.6, 131.0 (2C), 129.0,

113.3 (2C), 88.3, 54.9, 48.8, 38.1, 36.8, 32.9, 32.5, 27.4, 26.3, 10.7; HRMS (ESI): calcd for

C19H24O5S+ [M + H+]: 365.1423, found 365.1421.

1d: According to the general procedure, the reaction of diketone 9d (278 mg, 0.83 mmol),



in CH2Cl2 (8.3 mL) provided mesylate 1d (310 mg, 90% over two steps) as a white

amorphous powder (silica gel – CH2Cl2: EtOAc, 95:5). Rf = 0.3 (silica gel, cyclohexane:

EtOAc, 65:35); IR (film) ν 2925, 2855, 1694, 1674, 1638, 1451, 1178, 1099, 1072, 824 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.41 (d, J = 7.7 Hz, 1H), 6.90 – 7.16 (m, 3H), 4.62 (dd, J =

10.3, 8.0 Hz, 1H), 3.37 (d, J = 13.9 Hz, 1H), 3.02 (s, 3H), 2.83 (d, J = 13.9 Hz, 1H), 1.97 –

2.58 (m, 6H), 1.65 – 1.88 (m, 2H), 1.62 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 196.8, 158.8,

136.8, 133.0, 132.6, 132.3, 128.4, 126.8, 125.4, 88.1, 48.9, 38.2, 35.9, 32.4, 32.1, 27.1, 25.9,

O

OMs

MeO

O

OMs

Br

15

10.8; HRMS (ESI): calcd for C18H22O4SBr+ [M + H+]: 413.0422 and 415.0402, found

413.0418 and 415.0412.

16

1e: According to the general procedure, the reaction of diketone 9e (1.11 g, 3.7 mmol),



in CH2Cl2 (37 mL) provided mesylate 1e (1.25 g, 90% over two steps) as a light yellow

amorphous powder (silica gel – CH2Cl2: EtOAc / 95:5). Rf = 0.3 (silica gel, cyclohexane:

EtOAc, 6:4); IR (film) ν 3375, 2936, 1659, 1531, 1350, 1176, 940, 846, 739 cm-1; 1H NMR

(300 MHz, CDCl3) δ 7.76 (dd, J = 8.2, 1.0 Hz, 1H), 7.48 (td, J = 7.4, 1.0 Hz, 1H), 7.38 (m,

2H), 4.68 (dd, J = 10.7, 8.0 Hz, 1H), 3.55 (d, J = 14.0 Hz, 1H), 3.39 (d, J = 14.0 Hz, 1H), 3.10

(s, 3H), 2.40 (m, 3H), 2.20 – 2.29 (m, 1H), 2.16 (dd, J = 18.2, 5.6 Hz, 1H), 1.89 (m, 2H), 1.71

(dd, J = 18.6, 6.0 Hz, 1H), 1.64 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 196.6, 158.9, 150.6,

133.8, 133.4, 132.5, 131.9, 128.4, 125.1, 87.6, 48.9, 38.4, 33.2, 32.6, 32.5, 27.3, 26.1, 11.1;

HRMS (ESI): calcd for C18H22NO6S+ [M + H+]: 380.1168, found 380.1167.

1f: According to the general procedure, the reaction of diketone 9f (408 mg, 2.0 mmol),


The reaction of the crude alcohol, Et3N (0.84 mL, 6.0 mmol) and MsCl (232 µL, 3.0 mmol) in

CH2Cl2 (20 mL) provided mesylate 1f (448 mg, 79% over two steps) as a white amorphous

powder (silica gel – CH2Cl2: EtOAc / 9:1). Rf = 0.4 (silica gel, cyclohexane: EtOAc, 6:4); IR

(film) ν 2933, 1655, 1352, 1331, 1174, 1015, 964, 928, 844, 757 cm-1; 1H NMR (300 MHz,

CDCl3) δ 5.71 – 5.91 (m, 1H), 4.93 – 5.11 (m, 2H), 4.60 (dd, J = 10.1, 7.9 Hz, 1H), 2.99 (s,

3H), 2.37 – 2.64 (m, 4H), 1.99 – 2.37 (m, 5H), 1.78 (ddd~dt, J = 13.6, 5.7 Hz, 1H), 1.62 (s,

3H); 13C NMR (75 MHz, CDCl3) δ 197.5, 161.8, 134.4, 130.5, 117.9, 87.9, 47.4, 38.1, 36.7,

32.5, 32.1, 27.4, 25.8, 10.6; HRMS (ESI): calcd for C14H21O4S+ [M + H+]: 285.1161, found

285.1160.

O

OMs

NO2

O

OMs

17

1g: According to the general procedure, the reaction of diketone 9g (224 mg, 0.85 mmol),

NaBH4 (16 mg, 0.43 mmol) in MeOH (8.5 mL) provided an intermediate crude alcohol.


in CH2Cl2 (8.5 mL) provided mesylate 1g (266 mg, 91% over two steps) as a white


EtOAc, 8:2); IR (film) ν 2925, 2856, 1658, 1354, 1331, 1175, 1010, 968, 931, 845, 734 cm-1; 1H NMR (300 MHz, CDCl3) δ 4.57 (dd, J = 10.1, 7.8 Hz, 1H), 2.97 (s, 3H), 2.19 – 2.64 (m,

6H), 2.10 (m, 1H), 1.73 (ddd~dt, J = 13.1, 5.7 Hz, 1H), 1.59 (s, 3H), 1.35 – 1.51 (m, 2H), 1.17

(s, 10H), 0.78 (t, J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 197.6, 163.1, 129.8, 88.1,

46.9, 38.0, 32.9, 32.3, 31.8, 31.5, 30.3, 28.8, 27.6, 25.9, 25.8, 22.3, 13.8, 10.6; HRMS (ESI):

calcd for C18H31O4S+ [M + H+]: 343.1943, found 343.1944.

1h: According to the general procedure, the reaction of diketone 9h (8.03 g, 45.1 mmol),



mmol) in CH2Cl2 (450 mL) provided mesylate 1h (9.15 g, 79% over two steps) as a white


EtOAc, 6:4); IR (film) ν 2933, 1651, 1331, 1173, 966, 890, 862 cm-1; 1H NMR (300 MHz,

CDCl3) δ 4.62 (dd, J = 10.3, 7.5 Hz, 1H), 3.05 (s, 3H), 2.27 – 2.75 (m, 5H), 2.07 – 2.23 (m,

2H), 1.87 (ddd~dt, J = 13.5, 5.7 Hz, 1H), 1.66 (s, 3H), 1.19 (s, 3H); 13C NMR (75 MHz,

CDCl3) δ 197.6, 163.0, 129.9, 87.2, 44.5, 38.3, 33.5, 32.8, 27.2, 25.3, 16.4, 10.7; HRMS

(ESI): calcd for C12H19O4S+ [M + H+]: 259.1004, found 259.1014.

O

OMs

O

OMs

18

1i: According to the general procedure, the reaction of diketone 9i (300 mg, 1.827 mmol),

NaBH4 (34.6 mg, 0.913 mmol) in MeOH (18 mL) provided the crude alcohol.


mmol) in CH2Cl2 (18 mL) provided mesylate 1i (355 mg, 80% over two steps) as a white


EtOAc, 6:4); IR (film) ν 2934, 1643, 1334, 1169, 1039, 962, 778, 523 cm-1; 1H NMR (300

MHz, CDCl3) δ 5.67 (s, 1H), 4.52 (dd, J = 10.1, 7.8 Hz, 1H), 2.95 (s, 3H), 2.68 (ddt, J = 19.5,

12.0, 2.5 Hz, 1H), 2.15 – 2.43 (m, 4H), 1.95 – 2.10 (m, 2H), 1.77 (ddd~dt, J = 13.5, 5.5 Hz,

1H), 1.10 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 197.6, 170.4, 123.6, 86.6, 44.4, 37.9, 33.3,

32.5, 26.5, 25.8, 15.9; MS (SCI): 244 [M]+

O

OMs

19

II) Abbreviations PTSA = p-toluenesulonic acid.

DBU = 1,8-Diazabicyclo[5.4.0]undec-7-ene.

EVK = Ethyl vinyl ketone

20

III) 1H and 13C NMR Spectra

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

4.00

1.98

5.01

2.41

3.42

7.107.127.147.167.187.19

-100102030405060708090100110120130140150160170180190200210ppm

26.48

30.06

117.01

125.43

127.85

128.08

139.87

196.88

196.93

1H NMR (300 MHz, CDCl3 & 2 drops of MeOD)

DOO

Aa

13C NMR (75 MHz, CDCl3 & 2 drops of MeOD)

21

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

4.00

2.02

2.91

3.98

2.4

3.6

7.37.37.37.37.37.37.37.47.47.67.67.77.77.77.77.77.7

-100102030405060708090100110120130140150160170180190200210ppm

26.9

30.2

117.1

124.9

125.5

126.1

127.3

127.6

131.8

133.4

137.6

208.5



DOO

Ab

22

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.99

2.01

3.00

2.00

1.96

2.38

3.32

3.66

6.666.70

7.067.11

-100102030405060708090100110120130140150160170180190200210220ppm

25.7

30.2

55.0

113.4

117.5

129.2

132.2

157.5

196.7



DOO

Ac

OMe

23

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5ppm

4.00

2.00

1.930.99

1.02

2.45

3.49

6.926.946.976.987.017.077.107.127.417.44

-100102030405060708090100110120130140150160170180190200210220ppm

27.2

30.3

114.9

124.4

127.0

127.3

129.2

132.2

138.2

197.2



DOO

Ad

Br

24

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

4.16

2.09

2.00

1.06

1.00

2.36

3.63

7.107.127.137.147.177.267.287.287.307.337.677.70

-100102030405060708090100110120130140150160170180190200210ppm

23.3

30.0

114.4

124.0

126.5

130.7

132.5

134.1

149.1



DOO

Ae

O2N

25

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

4.24

2.09

3.31

0.98

2.50

2.832.85

4.874.884.914.914.924.924.934.984.995.725.745.765.765.785.805.815.825.835.85

-100102030405060708090100110120130140150160170180190200210220ppm

25.9

31.3

114.9

116.3

136.1

13C NMR (75 MHz, MeOD)

1H NMR (300 MHz, MeOD)

DOO

Af

26

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5ppm

3.01

8.242.13

1.99

4.00

0.800.820.84

1.221.35

2.072.092.12

2.46

-100102030405060708090100110120130140150160170180190200210220ppm

14.0

20.9

22.6

28.0

29.1

29.5

30.3

31.8

118.5

13C NMR (75 MHz, CDCl3 & 2 drops of MeOD )

1H NMR (300 MHz, CDCl3 & 2 drops of MeOD )

DOO

Ag

27

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.00

3.99

3.991.91

1.98

2.00

3.00

0.880.910.93

1.821.841.881.901.911.932.282.302.332.442.48

2.83

6.916.926.936.936.947.117.127.137.13

-100102030405060708090100110120130140150160170180190200210ppm

7.4

28.3

35.6

36.0

36.2

42.7

60.9

127.0

128.3

129.5

134.9

210.1

216.8

13C NMR (75 MHz, CDCl3)

1H NMR (300 MHz, CDCl3)

OO

O

Ba

28

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.02

1.93

2.00

5.98

2.00

1.00

3.03

3.06

0.981.001.03

1.851.871.921.942.032.052.072.372.392.412.442.492.54

3.08

7.117.127.147.157.417.427.437.437.447.457.457.487.677.707.727.747.757.77

-100102030405060708090100110120130140150160170180190200210ppm

7.6

28.6

35.8

36.2

36.4

42.9

61.2

125.9

126.2

127.5

127.7

128.1

128.5

132.3

132.6

133.1

210.3

217.1



OO

O

Bb

29

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.05

4.04

4.04

1.96

2.02

3.05

2.00

2.01

0.910.930.96

1.881.891.901.911.941.941.962.302.322.342.46

2.81

3.69

6.676.706.866.89

-100102030405060708090100110120130140150160170180190200210ppm

7.5

28.2

35.7

36.2

36.4

42.2

55.0

61.1

113.7

126.9

130.6

158.6

210.3

217.3



OO

O OMe

Bc

30

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.00

2.14

5.93

2.02

1.96

1.950.99

0.99

0.810.840.86

1.881.891.901.932.202.212.222.242.332.51

2.99

6.936.936.956.977.057.057.077.087.107.107.367.397.39

-100102030405060708090100110120130140150160170180190200210ppm

7.3

27.1

35.5

35.7

36.1

40.5

59.7

125.0

127.1

128.6

131.2

132.9

134.5

210.1

214.8



OO

OBr

Bd

31

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.06

2.13

4.12

4.15

2.03

1.001.031.01

1.00

0.880.910.93

1.851.881.902.252.282.302.612.622.632.642.652.66

3.31

7.207.207.227.237.337.347.367.367.387.397.457.457.477.477.507.507.877.887.907.90

-100102030405060708090100110120130140150160170180190200210ppm

7.4

27.5

35.3

35.7

36.0

36.2

59.0

125.3

128.4

130.5

132.9

133.2

149.1

209.8

214.9


OO

OO2N

Be


32

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.11

2.07

6.21

4.23

2.06

1.00

0.900.930.95

1.811.841.862.242.272.302.312.322.342.362.522.542.552.572.592.602.652.702.722.732.762.762.79

4.975.005.035.445.465.475.495.505.515.525.525.545.555.57

-100102030405060708090100110120130140150160170180190200210ppm

7.5

26.9

35.6

35.8

36.0

39.4

59.3

120.0

131.0

210.6

215.6



OO

O

Bf

33

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.083.0910.35

2.06

2.00

3.97

4.01

0.650.670.690.780.810.830.920.940.961.031.081.371.421.671.691.71

2.162.182.212.232.452.482.482.532.542.562.582.592.612.642.652.652.68

-100102030405060708090100110120130140150160170180190200210ppm

7.3

13.7

22.2

24.0

26.9

28.5

29.5

31.3

34.7

35.3

35.5

35.9

59.0

210.1

215.9



OO

O

Bg

34

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.033.02

1.96

3.99

4.00

0.880.900.921.01

1.771.791.822.262.282.312.332.352.602.632.642.642.682.692.702.722.742.752.782.792.802.82

-100102030405060708090100110120130140150160170180190200210ppm

7.4

18.9

27.7

34.5

35.8

35.9

55.0

210.5

215.7



OO

O

Bh

35

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.251.07

6.17

1.97

2.00

3.09

1.811.921.931.941.951.961.971.981.991.992.012.022.022.172.172.182.192.212.222.222.232.232.242.262.292.322.352.372.432.432.452.452.492.492.512.512.552.572.602.682.702.712.732.963.003.033.07

7.027.037.047.047.257.267.277.277.277.28

-100102030405060708090100110120130140150160170180190200210ppm

10.9

25.6

28.4

32.6

36.6

42.8

54.2

127.3

128.5

129.5

131.0

135.7

162.0

197.6

218.4



O

9aO

36

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

4.91

3.04

3.02

1.96

1.00

2.94

2.97

1.691.711.761.801.841.872.092.112.132.142.172.192.382.402.452.462.482.492.512.522.542.552.572.602.622.63

3.003.053.093.13

7.067.087.387.397.417.437.657.687.707.727.737.75

-100102030405060708090100110120130140150160170180190200210ppm

10.6

25.4

28.1

32.3

36.2

42.5

54.0

125.7

126.0

127.3

127.3

127.7

128.0

130.7

132.0

132.9

133.1

161.8

197.2

218.1



O

9bO

37

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.96

2.101.941.012.02

1.97

3.00

2.00

1.96

1.661.681.711.731.751.921.982.032.032.052.072.082.092.142.152.172.192.202.362.382.442.462.482.502.552.572.802.842.882.92

3.67

6.686.716.846.87

0102030405060708090100110120130140150160170180190200210ppm

10.6

25.3

27.9

32.3

36.3

41.6

54.0

54.8

113.5

127.3

130.3

130.5

158.5

162.1

197.3

218.2



O

MeO

9cO

38

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

4.11

1.18

3.081.152.10

1.06

1.05

2.051.05

1.00

1.691.701.701.711.731.761.782.152.162.162.192.202.212.242.242.252.272.292.412.422.432.442.562.582.602.612.622.692.902.94

3.433.47

7.007.007.017.027.037.047.047.057.067.127.127.157.177.177.427.447.457.45

-100102030405060708090100110120130140150160170180190200210ppm

10.8

25.5

28.5

32.5

36.8

40.4

53.6

125.2

127.2

128.8

131.4

131.7

133.0

135.4

160.3

197.2

218.1



O

Br

9dO

39

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

4.21

1.18

5.28

1.09

1.04

1.00

1.10

2.02

1.00

1.741.771.811.841.841.872.152.162.422.462.472.502.512.532.532.552.572.603.143.21

3.903.97

7.327.337.367.367.477.477.507.517.547.557.587.597.627.637.667.677.977.978.018.01

-100102030405060708090100110120130140150160170180190200210ppm

11.0

25.3

27.3

32.3

36.6

52.9

125.3

128.6

130.8

131.9

133.0

133.2

149.3

160.2

196.8

217.2



O

NO2

9eO

40

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

4.11

1.07

8.36

2.04

1.00

1.641.651.681.701.721.752.092.102.112.302.312.322.352.372.382.382.412.422.442.462.482.602.612.662.672.762.802.812.83

5.025.025.055.085.095.585.605.615.615.635.645.665.665.675.695.695.705.72

-100102030405060708090100110120130140150160170180190200210ppm

10.6

24.7

26.4

32.1

35.6

39.2

52.5

119.2

130.3

131.9

161.7

197.5

216.4



O

O

9f

41

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.00

9.76

5.85

1.04

2.94

2.99

0.680.710.74

1.101.471.481.511.551.622.012.022.032.042.102.252.272.282.302.352.372.532.542.572.642.682.692.722.752.78

0102030405060708090100110120130140150160170180190200210ppm

10.4

13.7

22.2

24.1

24.4

25.6

28.6

29.5

31.4

32.2

34.4

35.2

52.1

129.4

162.7

197.4

216.5



O

9gO

42

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.12

2.881.011.03

3.00

2.92

1.281.771.771.801.821.841.861.892.032.042.052.052.072.082.092.102.342.352.362.372.412.422.432.442.452.452.462.482.492.502.512.512.542.562.572.602.622.712.712.742.752.762.762.792.812.812.822.822.832.852.852.882.882.902.912.922.922.962.96

-100102030405060708090100110120130140150160170180190200210ppm

10.7

21.1

24.4

28.7

32.7

35.3

48.8

129.7

162.4

197.8

217.5



O

9hO

43

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.042.20

6.33

1.044.04

1.00

1.973.00

1.721.781.781.821.901.921.962.102.112.142.162.172.222.232.242.252.292.312.322.332.342.352.362.382.40

2.902.953.003.033.043.09

4.654.684.694.72

7.097.107.117.127.197.207.207.217.227.237.24

-100102030405060708090100110120130140150160170180190200210ppm

10.9

26.4

27.6

32.7

33.1

37.8

38.3

49.0

88.4

126.8

128.1

130.3

132.0

137.3

160.8

197.4



1aO

OMs

44

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.63

1.23

6.25

3.091.181.05

1.00

0.992.071.023.12

1.751.871.891.911.941.961.982.112.122.142.162.202.222.242.262.292.302.322.342.372.402.412.432.442.453.033.073.123.163.20

4.674.694.704.73

7.217.227.247.247.437.447.457.467.597.697.727.747.777.787.80

-100102030405060708090100110120130140150160170180190200210ppm

10.9

26.5

27.6

32.7

33.2

37.9

38.3

49.2

88.4

125.7

126.1

127.3

127.5

127.5

128.4

128.9

132.0

132.1

133.0

135.0

161.0

197.2



1bO

OMs

45

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5ppm

3.082.30

6.30

1.011.073.01

3.24

1.00

2.13

2.02

1.721.771.771.811.851.891.911.941.962.142.162.172.182.202.242.242.262.272.312.322.332.332.352.382.862.902.963.003.05

3.76

4.654.684.694.72

6.746.777.007.03

-100102030405060708090100110120130140150160170180190200210ppm

10.7

26.3

27.4

32.5

32.9

36.8

38.1

48.8

54.9

88.3

113.3

129.0

131.0

131.6

158.3

160.9

197.1



1cO

OMs

MeO

46

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.18

1.87

6.13

1.07

2.94

1.03

1.00

3.14

1.04

1.621.661.691.751.761.821.842.002.032.102.152.192.212.232.252.272.422.462.522.552.802.873.023.343.40

4.574.614.624.66

6.956.966.986.997.027.037.067.067.077.107.107.397.43

-100102030405060708090100110120130140150160170180190200210ppm

10.8

25.9

27.1

32.1

32.4

35.9

38.2

48.9

88.1

125.4

126.8

128.4

132.3

132.6

133.0

136.8

158.7

196.8

1dO

OMs

Br



47

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.081.002.031.180.903.13

3.121.031.03

1.01

3.00

1.00

1.61.71.71.71.81.91.91.91.92.12.12.22.22.22.22.22.22.32.42.42.42.43.1

3.43.43.53.6

4.64.74.74.7

7.47.47.47.57.57.57.57.57.77.87.8

-100102030405060708090100110120130140150160170180190200210ppm

11.1

26.1

27.3

32.5

32.6

33.2

38.4

48.9

87.6

125.1

128.4

131.9

132.5

133.4

133.8

150.6

158.8

196.5



1eO

OMs

NO2

48

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5ppm

3.04

1.07

5.43

3.96

3.08

0.99

2.04

1.00

1.621.771.791.822.112.122.152.152.162.212.242.262.262.282.302.322.322.422.432.452.482.502.512.542.56

2.99

4.574.604.604.634.975.015.065.075.745.775.775.785.795.805.825.835.835.855.865.865.88

-100102030405060708090100110120130140150160170180190200210ppm

10.6

25.7

27.4

32.1

32.5

36.7

38.1

47.4

87.9

117.9

130.5

134.4

161.8

197.5



1fO

OMs

49

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.12

9.732.063.001.23

1.09

6.13

3.03

1.00

0.80.80.81.21.41.41.41.61.71.7

2.22.32.32.32.42.42.4

3.0

4.54.64.64.6

-100102030405060708090100110120130140150160170180190200210ppm

10.6

13.8

22.3

25.8

25.9

27.5

28.8

30.3

31.5

31.8

32.3

32.9

38.0

46.9

88.1

129.8

163.1

197.6



1gO

OMs

50

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.06

3.40

1.14

2.16

5.24

2.98

1.00

1.191.662.122.132.142.162.162.452.452.472.472.492.502.61

3.05

4.594.624.634.65

-100102030405060708090100110120130140150160170180190200210ppm

10.7

16.4

25.3

27.2

32.8

33.5

38.3

44.5

87.2

129.9

163.0

197.6



1hO

OMs

51


1iO

OMs

52

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.17

4.28

1.13

3.15

1.00

2.07

4.76

1.781.811.851.881.911.942.042.102.132.142.172.182.202.522.522.552.552.612.622.642.652.792.802.822.852.872.882.892.912.952.96

6.156.186.886.896.906.916.927.147.157.177.177.187.197.207.247.27

-100102030405060708090100110120130140150160170180190200210ppm

9.8

29.0

33.9

43.0

47.7

127.0

128.4

130.0

134.3

134.9

135.7

150.4

162.8

196.7

200.0



3aO

O

53

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.083.021.01

1.01

2.04

0.97

0.96

1.00

1.043.02

3.09

1.881.901.921.941.961.992.172.192.212.222.232.242.272.272.292.652.652.672.672.712.712.732.962.983.003.023.033.043.073.073.093.133.17

6.226.247.077.347.367.427.447.457.467.477.48

7.737.747.767.777.787.797.81

-100102030405060708090100110120130140150160170180190200210ppm

9.8

28.9

34.0

43.1

47.9

125.9

126.3

127.5

127.6

127.9

128.0

128.7

132.2

133.1

133.2

134.3

134.9

150.4

162.8

196.7

200.0



3bO

O

54

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.132.971.10

1.06

3.04

3.18

0.96

2.012.05

1.00

1.861.891.911.931.951.972.152.172.172.192.192.212.212.232.232.652.662.672.682.852.872.882.902.912.94

3.76

6.226.24

6.766.786.796.856.88

7.297.31

-100102030405060708090100110120130140150160170180190200210ppm

9.8

28.9

33.9

42.1

47.9

55.1

113.8

127.6

131.0

134.1

134.9

150.5

158.5

162.9

196.8

200.1



3cO

O

MeO

55

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.063.131.12

1.09

0.981.12

1.04

1.00

0.991.031.05

1.001.00

2.012.022.032.052.072.102.122.282.282.302.302.322.332.342.352.622.632.642.652.692.692.712.712.942.962.983.003.023.053.073.123.363.40

6.116.136.866.876.886.897.007.017.037.037.057.067.117.127.147.147.167.177.267.447.447.467.477.487.50

-100102030405060708090100110120130140150160170180190200210ppm

9.7

30.8

33.9

41.1

48.5

125.8

127.1

128.8

132.2

133.1

134.8

135.0

135.1

149.1

161.3

196.4

199.9



3dO

O

Br

56

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

4.38

1.04

1.07

1.05

1.110.95

0.97

1.02

2.021.04

1.00

2.042.062.082.102.122.152.172.292.312.312.332.342.352.722.732.742.752.882.94

3.503.543.553.60

6.056.07

6.936.936.956.967.357.367.367.37

7.857.857.877.88

-100102030405060708090100110120130140150160170180190200210ppm

9.8

31.1

33.8

38.1

48.6

125.1

128.4

130.7

132.7

133.6

135.1

135.4

148.7

150.0

160.9

196.1

199.5



3eO

O

NO2

57

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.173.081.181.141.091.211.07

2.15

1.03

0.95

0.99

1.851.871.901.921.941.962.022.122.182.182.202.202.222.222.242.242.272.302.322.342.432.452.472.502.512.512.532.532.572.582.592.602.692.712.742.762.782.802.825.005.005.055.065.095.125.545.575.585.595.605.625.66

6.336.35

7.437.45

-100102030405060708090100110120130140150160170180190200210ppm

9.8

29.0

33.6

41.1

46.8

119.6

132.3

134.2

135.1

150.2

162.8

197.2

200.2



3fO

O

58

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.31

11.22

2.22

1.13

4.02

1.09

1.02

0.97

1.00

0.820.840.86

1.201.621.641.891.912.122.132.142.15

2.492.502.512.522.562.562.582.582.692.712.732.752.772.802.82

6.346.36

7.427.44

-100102030405060708090100110120130140150160170180190200210ppm

9.7

13.9

22.4

25.2

28.9

29.7

29.8

31.5

33.7

36.5

46.8

133.6

135.0

150.9

163.4

197.5

200.4



3gO

O

59

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.04

0.971.083.14

1.09

1.03

0.98

1.00

1.321.982.022.032.042.052.072.10

2.502.512.532.542.592.602.622.632.682.712.742.782.812.842.87

6.246.27

7.477.50

-100102030405060708090100110120130140150160170180190200210ppm

9.6

23.8

31.4

33.8

43.5

133.6

150.9

165.2

197.4

200.2



3hO

O

60

3iO

O


61

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.263.881.281.001.041.021.09

1.071.06

4.97

1.891.901.911.931.951.961.981.981.992.002.042.042.052.062.072.102.102.112.182.212.252.282.432.442.452.462.502.502.512.522.612.632.662.672.692.722.732.842.872.912.922.943.183.233.263.293.33

7.127.137.147.157.177.197.20

-100102030405060708090100110120130140150160170180190200210ppm

10.0

33.3

33.8

39.5

45.3

50.8

52.4

124.7

125.4

127.2

127.4

136.2

140.3

145.1

151.1

200.6

208.1



15aO

O

H

62

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

5.741.251.151.10

2.07

1.10

1.00

1.022.162.201.00

2.112.122.152.152.172.172.202.212.222.232.242.322.352.382.412.572.572.622.632.642.642.762.782.812.822.832.84

3.153.183.203.443.50

3.833.863.89

7.377.397.467.487.497.517.517.527.537.547.557.557.577.587.737.767.787.887.897.91

-100102030405060708090100110120130140150160170180190200210ppm

10.1

33.9

34.1

40.7

44.8

49.3

52.4

123.5

123.7

125.4

126.6

128.2

128.7

130.0

133.1

136.2

137.3

140.9

151.2

200.8

208.3



15bO

O

H

63

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.364.201.36

1.081.102.08

1.091.02

1.021.051.00

2.032.042.082.092.162.172.182.282.312.342.352.372.552.602.612.622.632.732.752.782.792.922.942.972.983.003.03

3.353.413.453.483.51

7.087.107.137.207.227.267.377.40

-100102030405060708090100110120130140150160170180190200210ppm

10.1

33.6

33.7

41.1

45.4

51.3

51.7

120.5

123.6

129.2

130.7

136.8

140.9

146.9

150.4

200.4

207.5



15cO

O

H

Br

64

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.21

0.851.423.221.321.161.251.04

1.00

0.95

1.00

1.431.451.891.911.941.951.992.002.152.282.302.332.352.622.642.83

3.813.823.833.833.843.853.863.87

6.416.43

7.627.64

-100102030405060708090100110120130140150160170180190200210ppm

10.0

27.1

30.4

33.9

46.4

46.8

54.3

134.8

135.8

149.9

162.6

196.9

200.1

1H NMR (300 MHz, CDCl3), 1st diastereoisomer


16O

O

Cl

65

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

1.275.051.18

2.31

0.99

0.93

1.00

1.491.511.941.972.132.142.172.18

2.562.602.612.632.642.672.69

3.873.883.893.903.913.923.923.933.943.953.963.98

6.406.42

7.577.59

-100102030405060708090100110120130140150160170180190200210ppm

9.9

26.5

31.0

33.7

46.3

46.7

54.0

133.8

135.6

150.5

161.5

196.7

199.8

1H NMR (300 MHz, CDCl3), 2nd diastereoisomer


16'O

O

Cl

66

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0ppm

3.87

1.163.141.191.19

3.27

2.14

1.06

0.99

1.00

1.00

1.251.271.301.931.952.142.202.212.242.352.372.392.422.622.622.632.662.672.692.712.722.73

4.144.164.194.21

5.815.86

6.386.406.716.736.766.786.81

7.487.50

-100102030405060708090100110120130140150160170180190200210ppm

9.9

14.2

28.9

33.5

39.5

46.7

60.6

125.6

135.0

135.6

141.8

149.4

161.9

165.5

196.5

199.7



17O

O

COOEt

Metal-free Aerobic C-H Oxidation of Cyclic Enones · 2014-06-16 · 1 Metal-free Aerobic C-H...

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Transcript of Metal-free Aerobic C-H Oxidation of Cyclic Enones · 2014-06-16 · 1 Metal-free Aerobic C-H...