Electronic Supplementary Material (ESI) for Green Chemistry.

This journal is © The Royal Society of Chemistry 2014

Supporting Information

Efficient synthesis of tertiary α-hydroxy ketones through

CO2-promoted regioselective hydration of propargylic
alcohols

Haitao He,a Chaorong Qi,a, b,* Xiaohan Hu,a Yuqi Guana and Huanfeng
Jianga

a School of Chemistry and Chemical Engineering, South China University of Technology,

Guangzhou 510640, PR China.
b State Key Lab of Luminescent Materials and Devices, South China University of
Technology, Guangzhou 510640, P.R. China.

E-mail: [email protected]

List of Contents

A. General methods ..........................................................................................................S2

B. General procedure for the preparation of α-hydroxy ketones (2a-2t)..........................S2
C. Procedure for the preparation of the cyclic carbonate 6a from 1a...............................S2
D. Procedure for the preparation of 2a from 6a................................................................S3
E. Analytical data .............................................................................................................S3
F. NMR Spectra..............................................................................................................S14

S1
A. General methods
1H and 13C NMR spectra were recorded using a Bruker Avance 400 MHz NMR
spectrometer. The chemical shifts are referenced to signals at 7.26 and 77.0 ppm,
respectively, and chloroform is solvent with TMS as the internal standard. Mass spectra
were recorded on a Shimadzu GCMS-QP5050A spectrometer at an ionization voltage of
70 eV equipped with a DB-WAX capillary column (internal diameter: 0.25 mm, length:
30 m). GC–MS was obtained using electron ionization. The data of HRMS was carried out
on a high-resolution mass spectrometer (LCMS-IT-TOF). IR spectra were obtained either
as potassium bromide pellets or as liquid films between two potassium bromide pellets
with a Bruker Vector 22 spectrometer. Melting points were determined with a Büchi
Melting Point B-545 instrument. Compounds 1b-p were synthesized according to the
literature procedures.[1] Other substrates were commercially purchased and used without
further purification.

B. General procedure for the preparation of α-hydroxy ketones (2a-2t)

To a 15 mL polytetrafluoroethylene (PTFE) reaction vessel, the mixture of propargylic

alcohol 1 (0.5 mmol), AgOAc (0.05 mmol), DBU (0.25 mmol), H2O (0.3 mL) and MeCN
(1.0 mL) was added successively. The vessel was fixed into a stainless steel autoclave
with a pressure-regulating system. Then the autoclave was sealed and CO2 was introduced
from a cylinder. The reaction was carried out at the selected temperature under magnetic
stirring for 24 h and the pressure was kept constant during the reaction. As the reaction
was completed, the vessel was cooled with an ice bath and the pressure was released
slowly to atmospheric pressure. The residual material was diluted with diethyl ether (30
mL), dried over anhydrous MgSO4 and then filtered. The volatile compounds were
removed in vacuo and the crude residue was separated by column chromatography on
silica gel to give the desired product 2a-2t.

C. Procedure for the preparation of the cyclic carbonate 6a from 1a

To a 15 mL polytetrafluoroethylene (PTFE) reaction vessel, the mixture of propargylic

alcohol 1a (0.5 mmol), AgOAc (0.05 mmol), DBU (0.25 mmol), and extra dry MeCN (1.0
mL) was added successively. The vessel was fixed into a stainless steel autoclave with a
S2
pressure-regulating system. Then the autoclave was sealed and CO2 was introduced from a
cylinder. The reaction was carried out at 25°C under magnetic stirring for 24 h and the
pressure was kept constant during the reaction. As the reaction was completed, the vessel
was cooled with an ice bath and the pressure was released slowly to atmospheric pressure.
The residual material was diluted with diethyl ether and then filtered. The volatile
compounds were removed in vacuo and the crude residue was separated by column
chromatography on silica gel (petroleum / EtOAc = 4:1) to give 6a in 96% yield.

D. Procedure for the preparation of 2a from 6a

To a 15 mL Schlenk tube, the mixture of 6a (0.24 mmol), DBU (0.5 equiv.), H2O (0.3
mL) and MeCN (1.0 mL) was added successively. After sealing the tube, the reaction was
carried out at 90°C under magnetic stirring for 18 h. As the reaction was completed, the
residual material was diluted with diethyl ether (30 mL), dried over anhydrous MgSO4 and
then filtered. The volatile compounds were removed in vacuo and the crude residue was
separated by column chromatography on silica gel (petroleum / EtOAc = 2:1) to give 2a in
95% yield.

E. Analytical data
3-hydroxy-3-methyl-1-(pyridin-2-yl)butan-2-one (2a)
O
OH 1a (80.5mg, 0.5 mmol) was used and the reaction mixture was stirred at 90 oC
N
under 2 MPa of CO2 for 24 h. 2a was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 2:1) as a pale yellow oil in 91% yield (81.4 mg,

0.455 mmol). In CDCl3 solution keto and enol tautomers are present in a 89:11 ratio, and only NMR

data for the major ketone form is given. 1H NMR (400 MHz, CDCl3): δ = 8.50 (d, J = 4.4 Hz, 1 H),

7.69 (td, J = 7.7, 1.6 Hz, 1 H), 7.26 (d, J = 7.8 Hz, 1 H), 7.21 (dd, J = 7.1, 5.2 Hz, 1 H), 4.16 (s, 2 H),

1.37 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 212.6, 155.3, 148.7, 137.4, 124.3, 122.1, 76.79, 46.6,

26.8. IR (KBr): 3475, 2981, 2879, 1715, 1595, 1460, 1313, 1157, 989, 750 cm-1. HRMS EI (m/z): calcd

for C10H14NO2, 180.1019 [M + H]+; found 180.1029.

3-hydroxy-3,4-dimethyl-1-(pyridin-2-yl)pentan-2-one (2b)
O
OH
N 1b (94.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at 90 oC

under 2 MPa of CO2 for 24 h. 2b was obtained after purification by column

S3
chromatography on silica gel (petroleum / EtOAc = 2:1) as a pale yellow oil in 77% yield (72.8 mg,

0.385 mmol). In CDCl3 solution keto and enol tautomers are present in a 89:11 ratio, and only NMR

data for the major ketone form is given. 1H NMR (400 MHz, CDCl3): δ = 8.50 (d, J = 4.4 Hz, 1 H),

7.68 (t, J = 7.7 Hz, 1 H), 7.26 (d, J = 7.8 Hz, 1 H), 7.22 – 7.16 (m, 1 H), 4.19 (d, J = 13.9 Hz, 1 H),

4.01 (d, J = 13.9 Hz, 1 H), 2.13 – 2.02 (m, 1 H), 1.31 (s, 3 H), 1.01 (d, J = 6.7 Hz, 3 H), 0.80 (d, J = 6.8

Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 212.7, 154.8, 148.7, 137.2, 124.3, 122.0, 81.2, 47.0, 34.8,

23.5, 17.1, 16.1. IR (KBr): 3495, 2969, 2877, 1715, 1593, 1438, 1308, 1153, 1027, 751 cm-1. HRMS EI

(m/z): calcd for C12H18NO2, 208.1332 [M + H]+; found 208.1330.

O
3-hydroxy-3,5-dimethyl-1-(pyridin-2-yl)hexan-2-one (2c)
OH
N 1c (101.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at 90 oC

under 2 MPa of CO2 for 24 h. 2a was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 2:1) as a pale yellow oil in

80% yield (88.4 mg, 0.400 mmol). In CDCl3 solution keto and enol tautomers are present in a 90:10

ratio, and only NMR data for the major ketone form is given. 1H NMR (400 MHz, CDCl3): δ = 8.55 –

8.46 (m, 1 H), 7.69 (tt, J = 7.7, 1.9 Hz, 1 H), 7.27 (d, J = 7.8 Hz, 1 H), 7.21 (t, J = 5.6 Hz, 1 H), 4.22

(dd, J = 13.7, 1.6 Hz, 2 H), 4.07 (dd, J = 13.7, 1.3 Hz, 1 H), 1.82 – 1.75 (m, 1 H), 1.74 – 1.69 (m, 1 H),

1.65 – 1.60 (m, 1 H), 1.32 (d, J = 1.7 Hz, 3 H), 0.96 (dd, J = 6.5, 1.8 Hz, 3 H), 0.85 (dd, J = 6.5, 1.6 Hz,

3H). 13C NMR (100 MHz, CDCl3): δ =212.8, 154.9, 148.7, 137.4, 124.4, 122.1, 79.7, 48.1, 47.1, 26.7,

24.4, 24.2, 23.9. IR (KBr): 3494, 2956, 2870, 1713, 1640, 1595, 1474, 1367, 1276, 1153, 1030, 750

cm-1. HRMS EI (m/z): calcd for C13H20NO2, 222.1489 [M + H]+; found 222.1486.

O
3-ethyl-3-hydroxy-1-(pyridin-2-yl)pentan-2-one (2d)
OH
N 1d (94.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at 90 oC

under 2 MPa of CO2 for 24 h. 2d was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 2:1) as a pale yellow oil in 88% yield (91.1 mg,

0.440 mmol). In CDCl3 solution keto and enol tautomers are present in a 89:11 ratio, and only NMR

data for the major ketone form is given. 1H NMR (400 MHz, CDCl3): δ = 8.51 (s, 1 H), 7.68 (d, J = 1.7

Hz, 1 H), 7.23 (d, J = 25.0 Hz, 2 H), 4.06 (s, 2 H), 1.87 – 1.78 (m, 2 H), 1.76 – 1.67 (m, 2 H), 0.84 –

0.75 (m, 6 H). 13C NMR (100 MHz, CDCl3): δ =211.9, 154.5, 148.8, 137.1, 124.4, 122.0, 82.5, 47.0,

31.2, 7.6. IR (KBr): 3310, 2972, 2881, 1714, 1591, 1462, 1278, 1174, 975, 749 cm-1. HRMS EI (m/z):

calcd for C12H18NO2, 208.1332 [M + H]+; found 208.1338.

S4
 O
3-hydroxy-3-methyl-1-(pyridin-2-yl)nonan-2-one (2e)
OH
N 1e (115.5mg, 0.5 mmol) was used and the reaction mixture was stirred at 90
4
oC under 2 MPa of CO2 for 24 h. 2e was obtained after purification by

column chromatography on silica gel (petroleum / EtOAc = 2:1) as a pale yellow oil in 62% yield (77.2

mg, 0.310 mmol). In CDCl3 solution keto and enol tautomers are present in a 90:10 ratio, and only

NMR data for the major ketone form is given. 1H NMR (400 MHz, CDCl3): δ = 8.51 (s, 1 H), 7.68 (t, J

= 7.7 Hz, 1 H), 7.26 (d, J = 7.7 Hz, 1 H), 7.23 – 7.16 (m, 1 H), 4.17 (d, J = 13.7 Hz, 1 H), 4.07 (d, J =

13.6 Hz, 1 H), 1.80 – 1.73 (m, 1 H), 1.68 – 1.60 (m, 1 H), 1.45 – 1.39 (m, 1 H), 1.34 (s, 3 H), 1.29 –

1.21 (m, 6 H), 1.14 – 1.04 (m, 1 H), 0.86 (t, J = 6.5 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ =212.5,

154.9, 148.6, 137.3, 124.3, 122.0, 79.3, 46.9, 39.8, 31.6, 29.4, 25.6, 23.4, 22.4, 13.9. IR (KBr): 3495,

2929, 2855, 1714, 1594, 1472, 1436, 1153, 750 cm-1. HRMS EI (m/z): calcd for C15H24NO2, 250.1802

[M + H]+; found 250.1797.

O
3-hydroxy-3-isobutyl-5-methyl-1-(pyridin-2-yl)hexan-2-one (2f)
OH
N 1f (122.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at 90
oC under 2 MPa of CO2 for 24 h. 2f was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 10:1) as a pale yellow oil

in 71% yield (93.4 mg, 0.355mmol). In CDCl3 solution keto and enol tautomers are present in a 87:13

ratio, and only NMR data for the major ketone form is given. 1H NMR (400 MHz, CDCl3): δ = 8.52 (s,

1 H), 7.68 (t, J = 7.7 Hz, 1 H), 7.30 (d, J = 7.9 Hz, 1 H), 7.24 – 7.17 (m, 1 H), 4.13 (s, 2 H), 1.71 – 1.63

(m, 6 H), 0.95 (d, J = 5.9 Hz, 6 H), 0.82 (d, J = 5.9 Hz, 6 H). 13C NMR (100 MHz, CDCl3): δ = 212.6,

154.4, 148.8, 137.1, 124.4, 122.2, 82.9, 48.0, 47.1, 24.4, 24.2. IR (KBr): 3231, 2957, 2868, 1711, 1648,

1591, 1474, 1387, 1322, 1173, 1058, 998, 752, 510 cm-1. HRMS EI (m/z): calcd for C16H26NO2,

264.1958 [M + H]+; found 264.1957.

3-hydroxy-3-methyl-1-(pyridin-2-yl)pentan-2-one (2g)
O
OH 1g (87.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at 90 oC
N
under 2 MPa of CO2 for 24 h. 2g was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 2:1) as a pale yellow oil in 80% yield (77.2 mg,

0.400 mmol). In CDCl3 solution keto and enol tautomers are present in a 90:10 ratio, and only NMR

data for the major ketone form is given. 1H NMR (400 MHz, CDCl3): δ = 8.51 (d, J = 4.4 Hz, 1 H),

7.69 (t, J = 7.7 Hz, 1 H), 7.26 (d, J = 7.7 Hz, 1 H), 7.23 – 7.17 (m, 1 H), 4.12 (q, J = 13.7 Hz, 2 H),

S5
1.86 – 1.77 (m, 1 H), 1.73 – 1.65 (m, 1 H), 1.34 (s, 3 H), 0.86 (t, J = 7.4 Hz, 3 H). 13C NMR (100 MHz,

CDCl3): δ = 212.5, 154.9, 148.7, 137.4, 124.4, 122.0, 79.5, 46.9, 32.4, 25.2, 7.8. IR (KBr): 3498, 2986,

2938, 1723, 1648, 1596, 1480, 1381, 1322, 1153, 996, 935, 751 cm-1. HRMS EI (m/z): calcd for

C11H16NO2, 194.1176 [M + H]+; found 194.1173.

O
3-hydroxy-3-phenyl-1-(pyridin-2-yl)butan-2-one (2h)
OH
N 1h (111.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at 90
oC under 2 MPa of CO2 for 24 h. 2h was obtained after purification by

column chromatography on silica gel (petroleum / EtOAc = 2:1) as brown oil in 69% yield (83.1 mg,

0.345 mmol). In CDCl3 solution keto and enol tautomers are present in a 89:11 ratio, and only NMR

data for the major ketone form is given. 1H NMR (400 MHz, CDCl3): δ = 8.45 (d, J = 4.5 Hz, 1 H),

7.63 – 7.54 (m, 3 H), 7.34 (t, J = 7.5 Hz, 2 H), 7.26 (t, J = 7.2 Hz, 1 H), 7.20 – 7.06 (m, 2 H), 4.27 (d, J

= 13.8 Hz, 1 H), 3.72 (d, J = 13.8 Hz, 1 H), 1.73 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 208.8,

155.3, 148.5, 141.9, 137.5, 128.3, 127.5, 125.5, 124.3, 122.0, 80.4, 46.3, 26.8. IR (KBr): 3467, 3059,

2978, 2932, 1720, 1635, 1596, 1475, 1441, 1366, 1319, 1154, 1071, 1030, 753, 701 cm-1. HRMS EI

(m/z): calcd for C15H16NO2, 242.1176 [M + H]+; found 242.1173.

O
1-(1-hydroxycyclopentyl)-2-(pyridin-2-yl)ethanone (2i)
OH
N 1i (93.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at 90 oC

under 2 MPa of CO2 for 24 h. 2i was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 2:1) as a pale yellow oil in 82% yield (84.1 mg,

0.410 mmol). In CDCl3 solution keto and enol tautomers are present in a 94:6 ratio, and only NMR

data for the major ketone form is given. 1H NMR (400 MHz, CDCl3): δ = 8.48 (s, 1 H), 7.67 (t, J = 7.6

Hz, 1 H), 7.25 (d, J = 7.7 Hz, 1 H), 7.19 (dd, J = 6.4, 5.6 Hz, 1 H), 4.16 (s, 2 H), 2.00 – 1.85 (m, 4 H),

1.77 – 1.67 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 212.9, 155.2, 148.6, 137.5, 124.3, 122.1, 87.4,

47.9, 39.7, 25.0. IR (KBr): 3499, 2971, 2872, 1711, 1594, 1475, 1436, 1319, 1173, 1015, 751 cm-1.

HRMS EI (m/z): calcd for C12H16NO2, 206.1176 [M + H]+; found 206.1173.

O
1-(1-hydroxycyclohexyl)-2-(pyridin-2-yl)ethanone (2j)
OH
N 1j (100.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at 90 oC

under 2 MPa of CO2 for 24 h. 2j was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 2:1) as a pale yellow oil in 78% yield (85.4 mg,

0.390 mmol). In CDCl3 solution keto and enol tautomers are present in a 91:9 ratio, and only NMR

S6
data for the major ketone form is given. 1H NMR (400 MHz, CDCl3): δ = 8.49 (s, 1 H), 7.71 – 7.64 (m,

1 H), 7.27 – 7.16 (m, 2 H), 4.14 (s, 2 H), 1.75 – 1.66 (m, 4 H), 1.60 – 1.53 (m, 4 H), 1.41 – 1.10 (m, 2

H). 13C NMR (100 MHz, CDCl3): δ = 212.9, 155.5, 148.6, 137.5, 124.4, 122.0, 78.5, 47.0, 34.2, 25.3,

21.0. IR (KBr): 3445, 2930, 2856, 1710, 1595, 1476, 1439, 1265, 1158, 990, 751 cm-1. HRMS EI (m/z):

calcd for C13H18NO2, 220.1332 [M + H]+; found 220.1330.

O 3-hydroxy-3-methyl-1-(thiophen-2-yl)butan-2-one (2k)
OH
S 1k (83.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at 120 oC

under 2 MPa of CO2 for 24 h. 2k was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 10:1) as a brown oil in 76% yield (69.9 mg, 0.380

mmol). 1H NMR (400 MHz, CDCl3): δ = 7.22 (dd, J = 5.2, 1.1 Hz, 1 H), 6.97 (dd, J = 5.1, 3.5 Hz, 1

H), 6.90 (dd, J = 3.3, 0.8 Hz, 1 H), 4.10 (s, 2 H), 1.44 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 210.4,

134.6, 126.9, 126.8, 125.1, 76.7, 36.5, 26.5. IR (KBr): 3518, 2977, 2933, 1715, 1465, 1362, 1194, 1049,

968, 700 cm-1. HRMS EI (m/z): calcd for C9H12NaO2S, 207.0450 [M + Na]+; found 207.0447.

O 3-hydroxy-3,4-dimethyl-1-(thiophen-2-yl)pentan-2-one (2l)
OH
S 1l (97.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at 120 oC

under 2 MPa of CO2 for 24 h. 2l was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 10:1) as a brown oil in 70% yield (74.2 mg, 0.350

mmol). 1H NMR (400 MHz, CDCl3): δ = 7.23 (dd, J = 5.1, 1.1 Hz, 1 H), 6.97 (dd, J = 5.1, 3.5 Hz, 2

H), 6.91 (d, J = 2.6 Hz, 1 H), 4.05 (s, 2 H), 2.07 (dt, J = 13.5, 6.8 Hz, 1 H), 1.38 (s, 3 H), 1.04 (d, J =

6.7 Hz, 3 H), 0.76 (d, J = 6.8 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 210.9, 134.4, 127.0, 126.8,

125.2, 81.1, 36.8, 34.7, 23.3, 17.2, 15.8. IR (KBr): 3498, 2928, 2853, 1707, 1466, 1386, 1278, 1096,

1039, 748 cm-1. HRMS EI (m/z): calcd for C11H16NaO2S, 235.0763 [M + Na]+; found 235.0768.

O 1-(1-hydroxycyclopentyl)-2-(thiophen-2-yl)ethanone (2m)
OH
S 1m (96.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at 120 oC

under 2 MPa of CO2 for 24 h. 2m was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 10:1) as a brown oil in 51% yield (53.6 mg, 0.255

mmol). 1H NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 5.1 Hz, 1 H), 7.02 – 6.96 (m, 1 H), 6.93 (d, J =

3.1 Hz, 1 H), 4.10 (s, 2 H), 2.15 – 2.06 (m, 2 H), 2.02 – 1.93 (m, 2 H), 1.89 – 1.82 (m, 2 H), 1.80 – 1.73

(m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 210.0, 134.9, 126.8, 126.8, 125.1, 87.4, 39.1, 37.0, 25.3. IR

S7
(KBr): 3480, 2941, 2835, 1710, 1423, 1231, 1209, 743 cm-1. HRMS EI (m/z): calcd for C11H14NaO2S,

233.0607 [M + Na]+; found 233.0601.

3-hydroxy-3-methyl-1-phenylbutan-2-one (2n1)[2]
O
OH 1n1 (80.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at 120 oC

under 2 MPa of CO2 for 24 h. 2n1 was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 10:1) as a yellow oil in 67% yield (59.6 mg, 0.335

mmol). 1H NMR (400 MHz, CDCl3): δ = 7.33 (t, J = 7.2 Hz, 2 H), 7.28 (d, J = 7.0 Hz, 1 H), 7.20 (d, J

= 7.3 Hz, 2 H), 3.88 (s, 2 H), 1.44 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 211.8, 133.6, 129.5,

128.6, 127.1, 76.7, 42.4, 26.6. IR (KBr): 3499, 2980, 1713, 1365, 1276, 1190, 1051, 969, 751 cm-1. MS

(EI) m/z: 59, 65, 91, 120, 135, 150, 161, 178.

1-(4-fluorophenyl)-3-hydroxy-3-methylbutan-2-one (2n2)
F
O
OH 1n2 (89.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at 120
oC under 2 MPa of CO2 for 24 h. 2n2 was obtained after purification by

column chromatography on silica gel (petroleum / EtOAc = 10:1) as a yellow oil in 87% yield (85.2 mg,

0.435 mmol). 1H NMR (400 MHz, CDCl3): δ = 7.15 (dd, J = 7.2, 5.6 Hz, 2 H), 7.01 (td, J = 8.6, 1.6 Hz,

2 H), 3.85 (s, 2 H), 1.43 (d, J = 1.8 Hz, 6 H). 13C NMR (100 MHz, CDCl3): δ = 211.6, 161.9, 131.0,

129.3, 115.4, 76.6, 41.5, 26.5. IR (KBr): 3512, 2978, 2935, 1723, 1605, 1511, 1465, 1364, 1225, 1225,

1159, 1054, 970, 825, 793, 521 cm-1. HRMS EI (m/z): calcd for C11H13FNaO2, 219.0792 [M + Na]+;

found 219.0791.
Cl
O 1-(4-chlorophenyl)-3-hydroxy-3-methylbutan-2-one (2n3)
OH
1n3 (97.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at

120 oC under 2 MPa of CO2 for 24 h. 2n3 was obtained after purification by column chromatography

on silica gel (petroleum / EtOAc = 10:1) as a yellow solid in 78% yield (82.7 mg, 0.390 mmol); mp:

49-50 °C. 1H NMR (400 MHz, CDCl3): δ = 7.27 (d, J = 8.4 Hz, 2 H), 7.11 (d, J = 8.4 Hz, 2 H), 3.85 (s,

2 H), 1.40 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 211.4, 132.8, 132.1, 130.8, 128.8, 128.5, 76.6,

41.6, 26.4. IR (KBr): 3501, 2977, 2934, 1720, 1364, 1322, 1190, 1094, 1053, 970, 805, 775, 495 cm-1.

HRMS EI (m/z): calcd for C11H13ClNaO2, 235.0496 [M + Na]+; found 235.0491.

Br 1-(4-bromophenyl)-3-hydroxy-3-methylbutan-2-one (2n4)[3]
O
OH 1n4 (119.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at

120 oC under 2 MPa of CO2 for 24 h. 2n4 was obtained after purification by

S8
column chromatography on silica gel (petroleum / EtOAc = 10:1) in 76% yield (90.4 mg, 0.380 mmol).

Yellow solid; mp 57-58 °C. 1H NMR (400 MHz, CDCl3): δ = 7.47 – 7.42 (m, 2 H), 7.07 (d, J = 8.4 Hz,

2 H), 3.83 (s, 2 H), 1.43 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 211.2, 132.6, 131.62, 131.2, 121.1,

76.7, 41.7, 26.49. IR (KBr): 3510, 2978, 2933, 1715, 1489, 1364, 1322, 1191, 1049, 1012, 969, 771,

673, 489 cm-1. MS (EI) m/z: 59, 89, 170, 198, 213, 256.

O methyl 4-(3-hydroxy-3-methyl-2-oxobutyl)benzoate (2n5)

O O 1n5 (109.0 mg, 0.5 mmol) was used and the reaction mixture was stirred
OH
at 120 oC under 2 MPa of CO2 for 24 h. 2n5 was obtained after

purification by column chromatography on silica gel (petroleum / EtOAc = 10:1) in 85% yield (100.3

mg, 0.425 mmol). Yellow solid; mp 63-64 °C. 1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.2 Hz, 2

H), 7.27 (d, J = 8.1 Hz, 2 H), 3.95 (s, 2 H), 3.90 (s, 3 H), 1.43 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ

= 211.1, 166.8, 139.0, 129.7, 129.6, 128.9, 76.8, 52.0, 42.4, 26.5. IR (KBr): 3525, 2980, 1729, 1611,

1438, 1367, 1277, 1186, 1112, 1052, 968, 747, 564, 482 cm-1. HRMS EI (m/z): calcd for C13H16NaO4,

259.0941 [M + Na]+; found 259.0940.

3-hydroxy-3-methyl-1-(4-nitrophenyl)butan-2-one (2n6)
O2N
O
OH 1n6 (102.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at

120 oC under 2 MPa of CO2 for 24 h. 2n6 was obtained after purification

by column chromatography on silica gel (petroleum / EtOAc = 10:1) in 80% yield (89.2 mg, 0.400

mmol). Brown solid; mp 103-104 °C. 1H NMR (400 MHz, CDCl3): δ = 8.19 (dd, J = 8.6, 1.8 Hz, 2H),

7.38 (d, J = 8.4 Hz, 2H), 4.03 (s, 2H), 1.47 (d, J = 1.1 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ = 210.4,

147.1, 141.3, 130.5, 123.7, 76.9, 42.1, 26.6. IR (KBr): 3538, 3081, 2978, 2935, 1709, 1604, 1515, 1348,

1189, 1110, 970, 859, 734 cm-1. HRMS EI (m/z): calcd for C11H13NaO4, 246.0737 [M + Na]+; found

246.0731.

4-(3-hydroxy-3-methyl-2-oxobutyl)benzonitrile (2n7)
NC
O
OH 1n7 (92.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at

120 oC under 2 MPa of CO2 for 24 h. 2n7 was obtained after purification by

column chromatography on silica gel (petroleum / EtOAc = 10:1) as a yellow oil in 90% yield (81.2 mg,

0.450 mmol). 1H NMR (400 MHz, CDCl3): δ = 7.62 (d, J = 7.5 Hz, 2 H), 7.32 (d, J = 7.8 Hz, 2 H),

3.98 (s, 2 H), 1.45 (s, 6 H). 13C NMR (101 MHz, CDCl3): δ = 210.6, 139.3, 132.2, 130.4, 118.6, 110.9,

S9
76.8, 42.3, 26.5. IR (KBr): 3470, 2981, 2231, 2028, 1716, 1635, 1380, 1101, 741, 617 cm-1. HRMS EI

(m/z): calcd for C12H13NNaO2, 226.0838 [M + Na]+; found 226.0844.

O 3-hydroxy-1-(4-methoxyphenyl)-3-methylbutan-2-one (2n8)[4]
O
OH 1n8 (95.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at

120 oC under 2 MPa of CO2 for 24 h. 2n8 was obtained after purification by

column chromatography on silica gel (petroleum / EtOAc = 10:1) as a yellow oil in 61% yield (63.4 mg,

0.305 mmol). 1H NMR (400 MHz, CDCl3): δ = 7.12 (d, J = 8.1 Hz, 2 H), 6.87 (d, J = 7.9 Hz, 2 H),

3.82 (s, 2 H), 3.80 (s, 3 H), 1.43 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 212.1, 158.7, 130.4, 125.5,

114.1, 76.6, 55.2, 41.5, 26.6. IR (KBr): 3495, 2976, 2934, 1714, 1612, 1513, 1464, 1248, 1179, 1034,

789 cm-1. MS (EI) m/z: 59, 77, 91, 107, 121, 150, 208.

3-hydroxy-3-methyl-1-(2-nitrophenyl)butan-2-one (2o)
O
OH 1o (102.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at 120 oC

NO2 under 2 MPa of CO2 for 24 h. 2o was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 10:1) as a brown oil in 77% yield (85.9 mg, 0.385

mmol). 1H NMR (400 MHz, CDCl3): δ = 8.13 (d, J = 8.2 Hz, 1 H), 7.60 (td, J = 7.5, 1.0 Hz, 1 H), 7.51

– 7.45 (m, 1 H), 7.27 (d, J = 6.2 Hz, 1 H), 4.38 (s, 2 H), 1.52 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ

= 210.1, 148.8, 133.6, 133.5, 130.0, 128.5, 125.3, 76.8, 41.9, 26.9. IR (KBr): 3502, 3070, 2977, 2934,

1726, 1612, 1532, 1351, 1190, 1057, 968, 865, 788, 564 cm-1. HRMS EI (m/z): calcd for C11H13NaO4,

246.0737 [M + Na]+; found 246.0739.

O
3-hydroxy-3-methyl-1-(3-nitrophenyl)butan-2-one (2p)
OH
O2N 1p (102.5 mg, 0.5 mmol) was used and the reaction mixture was stirred at

120 oC under 2 MPa of CO2 for 24 h. 2p was obtained after purification by

column chromatography on silica gel (petroleum / EtOAc = 10:1) as a brown oil in 89% yield (99.2 mg,

0.445 mmol). 1H NMR (400 MHz, CDCl3): δ = 8.17 – 8.11 (m, 1 H), 8.08 (s, 1 H), 7.56 – 7.49 (m, 2

H), 4.04 (s, 2 H), 1.48 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 210.6, 148.3, 135.9, 135.7, 129.4,

124.6, 122.2, 76.8, 41.8, 26.6. IR (KBr): 3548, 3093, 2978, 2935, 1723, 1533, 1481, 1375, 1193, 1053,

970, 930, 806, 729, 677, 560 cm-1. HRMS EI (m/z): calcd for C11H13NaO4, 246.0737 [M + Na]+; found

246.0736.

O 1-(1-hydroxycyclohexyl)propan-1-one (2q)[5]
OH

S 10
1q (69.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at 120 oC under 2 MPa of CO2

for 24 h. 2q was obtained after purification by column chromatography on silica gel (petroleum /

EtOAc = 10:1) as a pale yellow oil in 46% yield (35.9 mg, 0.230 mmol). 1H NMR (400 MHz, CDCl3):

δ = 2.59 (q, J = 7.2 Hz, 2 H), 1.74 – 1.63 (m, 6 H), 1.52 – 1.43 (m, 2 H), 1.36 – 1.19 (m, 2 H), 1.10 (t, J

= 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 215.4, 77.9, 34.0, 28.9, 25.3, 21.1, 7.9. IR (KBr):

3465, 2027, 1635, 1384, 1102, 617 cm-1. MS (EI) m/z: 55, 79, 81, 99, 109, 156.

O 3-hydroxy-3-methylpentan-2-one (2r)[6]
OH
1r (49.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at 120 oC under 2

MPa of CO2 for 24 h. 2r was obtained after purification by column chromatography on

silica gel (petroleum / EtOAc = 10:1) as a pale yellow oil in 78% yield (45.2 mg, 0.390 mmol). 1H

NMR (400 MHz, CDCl3): δ = 2.23 (s, 3 H), 1.77 (q, J = 7.4 Hz, 2 H), 1.38 (s, 3 H), 0.85 (t, J = 7.4 Hz,

3 H). 13C NMR (100 MHz, CDCl3): δ = 212.4, 79.0, 32.2, 25.1, 23.6, 7.6. IR (KBr): 3320, 2945, 2853,

1739, 1668, 11463, 1383, 1260, 1090, 1021, 799, 749 cm-1. MS (EI) m/z: 55, 73, 87, 101, 116.

O 3-hydroxy-3-phenylbutan-2-one (2s)[7]
OH
1s (73.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at 120 oC

under 2 MPa of CO2 for 24 h. 2s was obtained after purification by column

chromatography on silica gel (petroleum / EtOAc = 10:1) as a brown oil in 72% yield (59.0 mg, 0.360

mmol). 1H NMR (400 MHz, CDCl3): δ = 7.44 (d, J = 7.4 Hz, 2 H), 7.37 (t, J = 7.4 Hz, 2 H), 7.31 (t, J =

7.1 Hz, 1 H), 2.08 (s, 3 H), 1.78 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 209.6, 141.4, 128.7, 128.0,

125.9, 79.8, 24.0, 23.4. IR (KBr): 3464, 2981, 2934, 1711, 1448, 1355, 1198, 1135, 1169, 914, 762,

701, 555 cm-1. MS (EI) m/z: 51, 77, 105, 121, 147, 164.

O 1-(1-hydroxycyclohexyl)ethanone (2t)[8]
OH
1t (62.0 mg, 0.5 mmol) was used and the reaction mixture was stirred at 120 oC under 2

MPa of CO2 for 24 h. 2t was obtained after purification by column chromatography on

silica gel (petroleum / EtOAc = 10:1) as yellow oil in 82% yield (58.2 mg, 0.410 mmol). 1H NMR (400

MHz, CDCl3): δ = 2.24 (s, 3 H), 1.73 – 1.64 (m, 6 H), 1.53 – 1.46 (m, 2 H), 1.39 – 1.16 (m, 2 H). 13C

NMR (100 MHz, CDCl3): δ = 212.7, 78.0, 33.8, 25.3, 23.7, 21.0. IR (KBr): 3394, 2924, 2852, 1714,

1670, 1464, 1408, 1260, 1095, 1020, 801, 749 cm-1. MS (EI) m/z: 55, 79, 81, 99, 109, 125, 142.

1-(biphenyl-4-yl)-3-hydroxy-3-methylbutan-2-one (3)

O
OH
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2n4 (59.5 mg, 0.25 mmol) was used and 3 was obtained after purification by column chromatography

on silica gel (petroleum / EtOAc = 10:1) in 82% yield (52.0 mg, 0.205 mmol). Yellow solid; mp 84-85

°C. 1H NMR (400 MHz, CDCl3): δ = 7.55 (t, J = 8.4 Hz, 4 H), 7.40 (t, J = 7.6 Hz, 2 H), 7.31 (t, J = 7.3

Hz, 1 H), 7.25 (d, J = 8.1 Hz, 2 H), 3.89 (s, 2 H), 1.43 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 211.8,

140.6, 139.9, 132.6, 129.8, 128.7, 127.2, 127.2, 126.9, 76.6, 42.0, 26.5. IR (KBr): 3450, 3057, 2979,

2936, 1697, 1488, 1371, 1267, 1194, 1057, 968, 754, 693 cm-1. HRMS EI (m/z): calcd for C17H18NaO2,

277.1199 [M + Na]+; found 277.1208.

H2N 1-(4-aminophenyl)-3-hydroxy-3-methylbutan-2-one (4)

O
OH 2n6 (55.7 mg, 0.25 mmol) was used and 4 was obtained after purification

by column chromatography on silica gel (petroleum / EtOAc = 2:1) in 95%

yield (45.8 mg, 0.237 mmol). Brown solid; mp 106-107 °C. 1H NMR (400 MHz, CDCl3): δ = 6.98 (d,

J = 8.1 Hz, 2 H), 6.64 (d, J = 8.1 Hz, 2 H), 3.75 (s, 2 H), 3.65 (s, 3 H), 1.41 (s, 6 H). 13C NMR (100

MHz, CDCl3): δ = 212.4, 145.4, 130.2, 123.2, 115.3, 76.5, 41.6, 26.6. IR (KBr): 3491, 2976, 2029,

1711, 1631, 1518, 1210, 1101, 741, 616 cm-1. HRMS EI (m/z): calcd for C11H16NO2, 194.1176 [ M + H

]+; found 194.1187.

O2N 3-methyl-1-(4-nitrophenyl)butane-2,3-diol (5)

OH
OH
2n6 (55.7 mg, 0.25 mmol) was used and 5 was obtained after purification by

column chromatography on silica gel (petroleum / EtOAc = 2:1) in 70%

yield (39.4 mg, 0.175 mmol). Yellow solid; mp 116-117 °C. 1H NMR (400 MHz, CDCl3): δ = 8.16 (d,

J = 8.1 Hz, 2 H), 7.43 (d, J = 8.2 Hz, 2 H), 3.63 (d, J = 10.5 Hz, 1 H), 2.95 (d, J = 13.8 Hz, 1 H), 2.71

(dd, J = 13.6, 10.9 Hz, 1 H), 2.11 (s, 2 H), 1.30 (d, J = 13.6 Hz, 6 H). 13C NMR (100 MHz, CDCl3): δ =

147.4, 146.7, 130.1, 123.6, 78.8, 72.9, 38.0, 26.5, 23.8. IR (KBr): 3465, 2980, 1635, 1517, 1346, 1104,

689, 616 cm-1. HRMS EI (m/z): calcd for C11H15NNaO4, 248.0893 [ M + Na ]+; found 248.0886.

O (Z)-4,4-dimethyl-5-((pyridin-2-yl)methylene)-1,3-dioxolan-2-one
O O (6a)[9]
2a (40.3 mg, 0.25 mmol) was used and 6a was obtained after purification by
N
column chromatography on silica gel (petroleum / EtOAc = 4:1) as a yellow oil

in 96% yield (49.2 mg, 0.240 mmol). 1H NMR (400 MHz, CDCl3): δ = 8.54 (d, J = 4.4 Hz, 1 H), 7.85

(d, J = 8.1 Hz, 1 H), 7.70 (td, J = 8.0, 1.5 Hz, 1 H), 7.13-7.16 (m, 1 H), 5.81 (s, 1 H), 1.70 (s, 7 H). 13C

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NMR (100 MHz, CDCl3): δ = 153.6, 151.9, 150.8, 149.2, 136.6, 123.5, 122.0, 102.8, 85.8, 27.5. MS

(EI) m/z: 64, 78, 92, 118, 132, 146, 160, 205.

References

[1] (a) T. Schwier, M. Rubin and V. Gevorgyan, Org. Lett., 2004, 6, 1999; (b) Z. Novák, A. Szabó, J.

Répási and A. Kotschy, J. Org. Chem., 2003, 68, 3327; (c) D. Chernyak, S. B. Gadamsetty and V.

Gevorgyan, Org. Lett., 2008, 10, 2307.

[2] R. Ramage, G. J. Griffiths, F. E. Shutt and J. N. A. Sweeney, J. Chem. Soc., Perkin Trans. 1. 1984,

1531.

[3] A. R. Katritzky, K. A. Heck, J. Li, A. Wells and C. Garot, Syn. Commun., 1996, 26, 2657.

[4] J. R. Rhodes, U.S. Patent. 5, 508, 310, 1996.

[5] M. Murakami, T. Kawano, H. Ito and Y. Ito, J. Org. Chem. 1993, 58, 1458.

[6] I. K. Meier and J. A. Marsella, J. Mol. Catal., 1993, 78, 31.

[7] N. Kise, S. Agui, S. Morimoto and N. Ueda, J. Org. Chem., 2005, 70, 9407.

[8] T. Maki, S. Iikawa, G. Mogami, H. Harasawa, Y. Matsumura and O. Onomura, Chem. Eur. J., 2009,

15, 5364.

[9] Y. B. Wang, Y. M. Wang, W. Z. Zhang and X. B. Lu, J. Am. Chem. Soc., 2013, 135, 11996.

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F. NMR Spectra

3-hydroxy-3-methyl-1-(pyridin-2-yl)butan-2-one (2a)

S 14
3-hydroxy-3,4-dimethyl-1-(pyridin-2-yl)pentan-2-one (2b)

S 15
3-hydroxy-3,5-dimethyl-1-(pyridin-2-yl)hexan-2-one (2c)

S 16
3-ethyl-3-hydroxy-1-(pyridin-2-yl)pentan-2-one (2d)

S 17
3-hydroxy-3-methyl-1-(pyridin-2-yl)nonan-2-one (2e)

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3-hydroxy-3-isobutyl-5-methyl-1-(pyridin-2-yl)hexan-2-one (2f)

S 19
3-hydroxy-3-methyl-1-(pyridin-2-yl)pentan-2-one (2g)

S 20
3-hydroxy-3-phenyl-1-(pyridin-2-yl)butan-2-one (2h)

S 21
1-(1-hydroxycyclopentyl)-2-(pyridin-2-yl)ethanone (2i)

S 22
1-(1-hydroxycyclohexyl)-2-(pyridin-2-yl)ethanone (2j)

S 23
3-hydroxy-3-methyl-1-(thiophen-2-yl)butan-2-one (2k)

S 24
3-hydroxy-3,4-dimethyl-1-(thiophen-2-yl)pentan-2-one (2l)

S 25
1-(1-hydroxycyclopentyl)-2-(thiophen-2-yl)ethanone (2m)

S 26
3-hydroxy-3-methyl-1-phenylbutan-2-one (2n1)

S 27
1-(4-fluorophenyl)-3-hydroxy-3-methylbutan-2-one (2n2)

S 28
1-(4-chlorophenyl)-3-hydroxy-3-methylbutan-2-one (2n3)

S 29
1-(4-bromophenyl)-3-hydroxy-3-methylbutan-2-one (2n4)

S 30
methyl 4-(3-hydroxy-3-methyl-2-oxobutyl)benzoate (2n5)

S 31
3-hydroxy-3-methyl-1-(4-nitrophenyl)butan-2-one (2n6)

S 32
4-(3-hydroxy-3-methyl-2-oxobutyl)benzonitrile (2n7)

S 33
3-hydroxy-1-(4-methoxyphenyl)-3-methylbutan-2-one (2n8)

S 34
3-hydroxy-3-methyl-1-(2-nitrophenyl)butan-2-one (2o)

S 35
3-hydroxy-3-methyl-1-(3-nitrophenyl)butan-2-one (2p)

S 36
1-(1-hydroxycyclohexyl)propan-1-one (2q)

S 37
3-hydroxy-3-methylpentan-2-one (2r)

S 38
3-hydroxy-3-phenylbutan-2-one (2s)

S 39
1-(1-hydroxycyclohexyl)ethanone (2t)

S 40
1-(biphenyl-4-yl)-3-hydroxy-3-methylbutan-2-one (3)

S 41
1-(4-aminophenyl)-3-hydroxy-3-methylbutan-2-one (4)

S 42
3-methyl-1-(4-nitrophenyl)butane-2,3-diol (5)

S 43
(Z)-4,4-dimethyl-5-(pyridin-2-ylmethylene)-1,3-dioxolan-2-one (6a)

S 44