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Supporting Information

Zirconocene-Catalyzed Direct (trans)Esterification of Acyl

Acids(Esters) and Alcohols in a Strict 1:1 Ratio under

Solvent-Free Conditions Zhi Tang,a† Qiutao Jiang,b† Lifen Peng,a† Xinhua Xu,a* Jie Li,b* Renhua Qiua* and Chak-Tong Au,c

aState Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China; b College of Chemistry and Chemical Engineering, Central South University, Changsha, China, cHunan Institute of Engineering, Xiangtan, P.R. China

Correspondence to: E-mail: renhuaqiu@hnu.edu.cn (R. Q.), xhx1581@hnu.edu.cn (X. X), 81485667@qq.comFax: +86-731-88821546

List of contents

S0 General method S2

S1 X-Ray and TG-DSC analysis of comlex Cp2Zr(Opf)2 S2

S2 1H NMR spectra and 19F NMR spectra of the fresh catalyst S4

S3 1H NMR spectra of the recycled catalyst S5

S4 Experimental section S6

S5 1H NMR spectra and 13C NMR spectra data of all compounds S8

S6 NMR spectra of all compounds S21

Electronic Supplementary Material (ESI) for Green Chemistry.This journal is © The Royal Society of Chemistry 2017

2 / 67

S0. General method

All chemicals were purchased from Aldrich. Co. Ltd and used as received unless otherwise indicated. The preparation of catalyst was carried out under nitrogen atmosphere with freshly distilled solvents unless otherwise noted. THF and hexane were distilled from sodium/benzophenone. Acetonitrile was distilled from CaH2. The NMR spectra were recorded at 25 °C on INOVA-400M (USA) calibrated with tetramethylsilane (TMS) as an internal reference. Elemental analyses were performed by VARIO EL III. TG-DSC analysis was performed on a HCT-1 (HENVEN, Beijing, China) instrument. X-ray single crystal diffraction analysis was performed using the SMART-APEX and RASA-7A equipment at Shanghai Institute Organic Chemistry, China Academy of Science. The acidity was measured by Hammett indicator method as described previously. Acid strength was expressed in terms of Hammett acidity function (Ho) as scaled by pKa value of the indicators.

S1. X-Ray and TG-DSC anaylsis of complex Cp2Zr(OPf)2 s1

C30H24F34O10S2Zr, Prismatic, colorless, Mr = 1345.83, Dx = 1.905 Mg m−3, Triclinic, P¯1, a = 9.9295 (13) Å, b = 11.9551 (16) Å, c = 20.269 (3) Å, α = 82.833 (3)°, β = 79.491 (3)°, γ = 87.397 (3)°, V = 2346.7 (5) Å3, Z = 2, θ = 1.7–25.5°, 0.50 × 0.24 × 0.21 mm,T = 293 (2) K, measured reflections/independent reflections 12436/8583, Rint = 0.104, h = −12-11,k = −14-11, l = −24-22, R1 = 0.095,wR2 = 0.277, S = 0.95.CCDC No. 631296.

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Figure S1. ORTEP representative of X-ray structure of catalyst 1

As depicted in Figure S2, the TG curve shows three stages of weight loss. The

endothermic step below 220˚C can be assigned to the removal of water molecules.

The material is stable up to about 300˚C, after which two overlapping weight losses of

exothermic nature appear, plausibly due to the oxidation of organic entities. We

observed the removal of perfluorooctanesulfuryl ligands at 400˚C, and what left

behind should be compounds of zirconium fluorides.

Figure S2 TG-DSC curves of complex Cp2Zr(OH2)3(OSO2C8F17)2·THF.

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S2. 1H NMR spectra and 19F NMR spectra of the fresh catalyst

Catalyst 11H NMR (400 MHz, Acetone): δ = 6.76 (s, 10 H, CpH), 3.63 (t, J = 5.6 Hz, 4 H, THF), 1.82 – 1.76 (m, 4 H, THF); 19F NMR (376 MHz; Acetone): δ = -81.65 (t, J = 9.8 Hz, 3 F, CF3–), -115.02 (s, 2 F, –CF2–), -121.05 (s, 2 F, –CF2– ), -122.17 – -122.48 (m, 6 F, –(CF2)3–), -123.28 (s, 2 F, –CF2–), -126.75 – -126.82 (m, 2 F, –CF2–).

Figure S3 1H NMR spectra of the fresh catalyst 1

5 / 67

Figure S4 19F NMR spectra of the fresh catalyst 1

6 / 67

S3. 1H NMR spectra of the recycled catalyst

After the reaction finished, the catalyst could be easily recovered from the system

as deposit upon the addition of 5 mL of CH2Cl2 for the next cycle.

recycled catalyst 1

1H NMR (400 MHz, Acetone): δ = 6.76 (s, 10 H, CpH),

7 / 67

S4. Experimental Section

Preparation of Cp2Zr(H2O)3(OSO2C8F17)2·THF (1)s1

To a solution of Cp2ZrCl2 (292 mg, 0.99 mmol) in THF (20 mL) was added a

solution of AgOSO2C8F17 (1.21 g, 2.0 mmol) in THF (10 mL). The mixture was

stirred in the dark at 25 °C for 1 h, and subject to filtration. The filtrate was combined

with dry hexane (40 mL). Then, the solution was stored in the refrigerator for 24 h to

furnish colorless crystals of 1·THF(794 mg, 65%): M.p.133-136 °C. 1H NMR (400

MHz, Acetone-d6): δ = 6.76 (s, 10 H, CpH), 3.63 (t, J = 5.6 Hz, 4 H, THF), 1.82 –

1.76 (m, 4 H, THF); 19F NMR (376 MHz; Acetone): δ = -81.65 (t, J = 9.8 Hz, 3 F,

CF3–), -115.02 (s, 2 F, –CF2–), -121.05 (s, 2 F, –CF2– ), -122.17 – -122.48 (m, 6 F, –

(CF2)3–), -123.28 (s, 2 F, –CF2–), -126.75 – -126.82 (m, 2 F, –CF2–). Elemental

analysis for Cp2Zr(OSO2C8F17)2 after pumping for a week: calcd. (%) for

C26H10F34O6S2Zr: C, 25.60; H, 0.83; found: C, 25.67; H, 0.82. Elemental analysis for

Cp2Zr(OSO2C8F17)2·4H2O after standing in open air for 2 days: calcd (%) for

C26H18F34O10S2Zr: C, 24.18; H, 1.40; found: C, 24.34; H, 1.33. C30H24F34O10S2Zr,

Prismatic, colorless, Mr = 1345.83, Dx = 1.905 Mg m−3, Triclinic, P¯1, a = 9.9295

(13) Å, b = 11.9551 (16) Å, c = 20.269 (3) Å, α = 82.833 (3)°, β = 79.491 (3)°, γ =

87.397 (3)°, V = 2346.7 (5) Å3, Z = 2, θ = 1.7–25.5°, 0.50 × 0.24 × 0.21 mm,T = 293

(2) K, measured reflections/independent reflections 12436/8583, Rint = 0.104, h =

−12-11,k = −14-11, l = −24-22, R1 = 0.095,wR2 = 0.277, S = 0.95.CCDC No. 631296.

Typical procedure for direct esterification of alcohol with carboxylic acid using

catalyst 1.

To a round-bottom flask was added 2-phenylethanol (122 mg, 1.0 mmol) and 1

equivalent of acetic acid (60 mg, 1.0 mmol) and catalyst 1 (12.6 mg, 0.01 mmol, 1.0

mol% relative to 2-phenylethanol). The mixture was stirred at 80°C for 30 min and

monitored by TLC. Then the mixture was diluted with petroleum ether (10 mL × 3).

By means of filtration, the catalyst was separated and used for the next cycle, and the

filtrate was washed twice with 10 mL of saturated brine, and extracted by petroleum

ether (10 mL × 2). Subsequently the portions of petroleum ether were combined

together, dried by sodium sulfate, and evaporated to obtain the crude ester. Finally,

8 / 67

the ester was subject to short flash column chromatography on silica gel (petroleum

ether: ethyl acetate = 8:1, Rf = 0.7) to afford the colorless liquid, 162 mg, yield, 99%.

Typical procedure for transesterification of alcohol with carboxylic acid using

catalyst 1.

To a round-bottom flask was added 2-phenylethanol (122 mg, 1.0 mmol) and 1

equivalent of methyl propionate (88 mg, 1.0 mmol) and catalyst 1 (12.6 mg, 0.01

mmol, 1.0 mol% relative to 2-phenylethanol). The mixture was stirred at 65°C for 6 h

and monitored by TLC. Then the mixture was diluted with petroleum ether (10 mL ×

3). By means of filtration, the catalyst was separated and used for the next cycle, and

the filtrate was washed twice with 10 mL of saturated brine, and extracted by

petroleum ether (10 mL × 2). Subsequently the portions of petroleum ether were

combined together, dried by sodium sulfate, and evaporated to obtain the crude ester.

Finally, the ester was subject to short flash column chromatography on silica gel

(petroleum ether: ethyl acetate = 8:1, Rf = 0.7) to afford the colorless liquid, 160 mg,

yield, 90%.

S5. 1H NMR and 13C NMR Spectral Data of All Compounds

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O

O

Acetic acid 2–phenylethyl ester s2(4a)

1H NMR (400 MHz, Acetone): δ = 7.18–7.29 (m, 5 H), 4.26 (t, J = 7.2 Hz, 2 H), 2.90

(t, J = 7.0 Hz, 2 H), 1.99 (s, 3 H); 13C NMR (400 MHz, Acetone): δ = 170.67, 137.62,

128.66, 128.27, 126.33, 64.68, 34.88, 20.65. Ms (EI): m/z = 164.1 [M+H]+ .

O

O

Acetic acid 3–phenylpropyl ester s3(4b)

1H NMR (400 MHz, Acetone): δ = 7.17–7.30 (m, 5 H), 4.08 (t, J = 6.6 Hz, 2 H), 2.68

(t, J = 7.8 Hz, 2 H), 2.04 (s, 3 H), 1.92–1.99 (m, 2 H); 13C NMR (400 MHz, Acetone):

δ =171.15, 141.22, 128.45, 128.40, 126.02, 63.84, 32.19, 30.19, 20.96. Ms (EI): m/z =

178.1 [M+H]+ .

Acetic acid benzyl ester s4(4c)

1H NMR (400 MHz, Acetone): δ = 7.31–7.36 (m, 5 H), 5.10 (s, 2 H), 2.09 (s, 3 H);

13C NMR (400 MHz, Acetone): δ = 170.75, 135.86, 128.46, 128.15, 66.20, 20.89.

Ms (EI): m/z = 150.1 [M+H]+ .

O

O

Phenyl acetate s5(4d)1H NMR (400 MHz, Acetone): δ = 7.33–7.37 (m, 2 H), 7.18–7.22 (m, 1 H), 7.06–7.08

(m, 2 H), 2.25 (s, 3 H); 13C NMR (400 MHz, Acetone): δ = 169.24, 150.60, 129.25,

125.64, 121.42, 20.92, Ms (EI): m/z = 136.1 [M+H]+ .

O

O

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O

O

Benzhydryl acetate s6(4e)1H NMR (400 MHz, CDCl3) δ 7.28 – 7.16 (m, 10H), 6.81 (s, 1H), 2.07 (s, 3H); 13C

NMR (100 MHz, CDCl3) δ 170.03, 140.25, 128.53, 127.93, 127.13, 76.75, 21.29.

Ms (EI): m/z = 226.1 [M+H]+ .

O

O

cyclohexyl acetate s6(4f)

1H NMR (400 MHz, CDCl3) δ 4.80 – 4.62 (m, 1H), 2.00 (s, 3H), 1.82 (d, J = 10.3 Hz,

2H), 1.70 (m, 2H), 1.57 – 1.43 (m, 1H), 1.37 (m, 4H), 1.23 (m, 1H). 13C NMR (100

MHz, CDCl3) δ 170.56, 72.65, 31.63, 25.36, 23.78, 21.39. Ms (EI): m/z = 142.1

[M+H]+ .

O

O

O

O

propane-1,3-diyl diacetate s7(4g)

1H NMR (400 MHz, CDCl3) δ 4.10 (t, J = 6.3 Hz, 4H), 2.00 (s, 6H), 1.95 – 1.88 (m,

2H). 13C NMR (100 MHz, CDCl3) δ 170.93, 60.98, 27.85, 20.80. Ms (EI): m/z =

160.1 [M+H]+ .

O

O

methyl cyclopentanecarboxylate s8(4i)

1H NMR (400 MHz, CDCl3) δ 3.63 (s, 3H), 2.69 (m, 1H), 1.84 (m, 2H), 1.80 – 1.61

(m, 4H), 1.53 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 177.21, 51.49, 43.65, 29.97,

25.75. Ms (EI): m/z = 128.1 [M+H]+ .

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O

O

Methyl oleate (4j)

1H NMR (400 MHz, Acetone): δ = 5.31 – 5.37 (m, 2 H), 3.65 (s, 3 H), 2.27-3.31 (m, 2

H), 1.98 – 2.06 (m, 4 H), 1.60 – 1.62 (m, 2 H), 1.26 – 1.30 (m, 20 H), 0.88 (t, J = 6.8

Hz, 3 H); 13C NMR (400 MHz, Acetone): δ = 174.00, 129.81, 129.57, 51.18, 29.57,

29.43, 29.22, 29.05, 29.03, 27.08, 27.05, 24.84, 22.57, 13.95. Ms (EI): m/z = 296.2

[M+H]+ .

O

O

methyl benzoate s19(4k)

1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.8 Hz, 2H), 7.55 (d, J = 7.5 Hz, 1H), 7.44

(t, J = 7.6 Hz, 2H), 3.92 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 167.14, 132.92,

130.16, 129.58, 128.37, 52.12. Ms (EI): m/z = 136.1 [M+H]+ .

O

OS

Br

methyl 5-bromotetrahydrothiophene-2-carboxylate s10(4l)

1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 3.9 Hz, 1H), 7.00 (d, J = 3.9 Hz, 1H), 3.80

(s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.57, 134.66, 133.70, 130.90, 120.26, 52.32.

Ms (EI): m/z = 219.1 [M+H]+ .

O

O

Butyl benzoate s11(4m)

1H NMR (400 MHz, Acetone): δ = 8.05 (d, J = 7.6 Hz, 2 H), 7.52 –7.56 (m, 1 H),

7.41 –7.45 (m, 2 H), 4.33 (t, J = 6.6 Hz, 2 H), 1.72 – 1.79 (m, 2 H), 1.44 – 1.53 (m, 2

H), 0.98 (t, J = 7.4 Hz, 3 H); 13C NMR (400 MHz, Acetone): δ = 166.69, 132.78,

130.55, 129.53, 128.31, 64.83, 30.79, 19.28, 13.76. Ms (EI): m/z = 178.1 [M+H]+ .

O

O

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Hexyl benzoate s12(4n)

1H NMR (400 MHz, Acetone): δ = 8.03 – 8.05 (m, 2 H), 7.52 – 7.56 (m, 1 H), 7.41 –

7.45 (m, 2 H), 4.31 (t, J = 6.8 Hz, 2 H), 1.72 – 1.80 (m, 2 H), 1.43 – 1.46 (m, 2 H),

1.33 – 1.34 (m, 4 H), 0.90 (t, J = 6.8 Hz, 3 H); 13C NMR (400 MHz, Acetone):

δ = 166.68, 132.77, 130.57, 129.53, 128.31, 65.12, 31.48, 28.70, 25.72, 22.56, 14.00.

Ms (EI): m/z = 206.1 [M+H]+ .O

O

n-Heptyl benzoate s13(4o)1H NMR (400 MHz, Acetone): δ = 8.03 – 8.05 (m, 2 H), 7.48 – 7.52 (m, 1 H), 7.38 –

7.41 (m, 2 H), 4.30 (t, J = 6.8 Hz, 2 H), 1.71 – 1.78 (m, 2 H), 1.28 – 1.46 (m, 8 H),

0.89 (t, J = 7.0 Hz, 3 H); 13C NMR (400 MHz, Acetone): δ = 166.29, 132.49, 130.38,

129.30, 128.04, 64.83, 31.55, 28.78, 28.56, 25.83, 22.40, 13.83. Ms (EI): m/z = 220.1

[M+H]+ .O

O

n-Decyl benzoate s14(4p)

1H NMR (400 MHz, Acetone): δ = 8.11 – 8.13 (m, 2 H), 7.57 – 7.60 (m,1 H), 7.46 –

7.50 (m, 2 H), 4.38 (t, J = 6.6 Hz, 2 H), 1.79 – 1.86 (m, 2 H), 1.35 – 1.53 (m, 14 H),

0.96 (t, J = 6.6 Hz, 3 H); 13C NMR (400 MHz, Acetone): δ = 166.34, 132.52, 130.42,

129.35, 128.08, 64.89, 31.76, 29.40, 29.17, 29.16, 28.60, 25.91, 22.53, 13.93.

Ms (EI): m/z = 262.1 [M+H]+ .O

O

HO

n-Decyl 4-hydroxybenzoate (4q)1H NMR (400 MHz, Acetone): δ = 7.96 (d, J = 8.4 Hz, 2 H), 6.86 (d, J = 8.8 Hz, 2 H),

5.52 (s, 1 H), 4.28 (t, J = 6.6 Hz, 2 H), 1.73 – 1.75 (m, 2 H), 1.27 – 1.33 (m, 14 H),

0.88 (t, J = 6.8 Hz, 3 H); 13C NMR (400 MHz, Acetone): δ = 166.92, 161.19, 131.70,

121.86, 115.18, 64.83, 31.86, 29.58, 29.53, 29.40, 29.28, 25.71, 22.63, 14.02.

Ms (EI): m/z =278.1 [M+H]+ .

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O

O

Isobutyl benzoate s15(4r)

1H NMR (400 MHz, Acetone): δ = 8.06 (d, J = 7.2 Hz, 2 H), 7.54 (t, J = 7.4 Hz, 1 H),

7.41–7.44 (m, 2 H), 4.11 (d, J = 6.4 Hz, 2 H), 2.03 – 2.11 (m, 1 H), 1.02 (d, J = 6.8

Hz, 6 H); 13C NMR (400 MHz, Acetone): δ = 166.47, 132.68, 130.44, 129.42, 128.21,

70.87, 27.82, 19.08. Ms (EI): m/z = 178.2 [M+H]+ .

O

O

Prop-2-yn-1-yl benzoate s16(4t)

1H NMR (400 MHz, Acetone): δ = 8.08 (d, J = 7.6 Hz, 2 H), 7.59 (t, J = 7.4 Hz, 1 H),

7.46 (t, J = 7.6 Hz, 2 H), 4.93 (s, 2 H), 2.52 – 2.53 (m, 1 H); 13C NMR (400 MHz,

Acetone): δ = 165.84, 133.38, 129.83, 129.39, 128.47, 77.74, 75.03, 52.48.

Ms (EI): m/z = 160.1 [M+H]+ .

O

O

10–Undecenic acid 2–phenylethylester s17(4u)

1H NMR (400 MHz, Acetone): δ = 7.24 – 7.27 (m, 2 H), 7.16 – 7.19 (m, 3 H), 5.73 –

5.84 (m, 1 H), 4.95 – 5.00 (m, 1 H), 4.90 – 4.93 (m, 1 H), 4.26 (t, J = 7.0 Hz, 2 H),

2.89 (t, J = 7.0 Hz, 2 H), 2.24 (t, J = 7.6 Hz, 2 H), 2.02 (dd, J = 14.4, 7.2 Hz, 2 H),

1.57 – 1.58 (m, 2 H), 1.25 – 1.38 (m, 10 H); 13C NMR (400 MHz, Acetone):

δ = 173.57, 139.06, 137.93, 128.91, 128.48, 126.54, 114.25, 64.68, 35.22, 34.30,

33.85, 29.34, 29.27, 29.14, 29.12, 28.96, 24.97. Ms (EI): m/z = 288.2 [M+H]+ .

O

O

Phenylethyl acrylate (4v)

1H NMR (400 MHz, Acetone): δ = 7.29–7.32 (m, 2 H), 7.22–7.24 (m, 3 H), 6.38 (m,

1 H), 6.11 (m, 1 H), 5.81 (m, 1H), 4.37 (t, J = 7.2 Hz, 2 H), 2.98 (t, J = 7.2 Hz, 2 H);

13C NMR (400 MHz, Acetone): δ = 166.06, 137.74, 130.63, 128.86, 128.46, 126.53,

14 / 67

64.96, 35.07. Ms (EI): m/z = 176.1 [M+H]+ .

OBr

O

Bromoacetic acid 2–phenylethyl ester (4w)

1H NMR (400 MHz, Acetone): δ = 7.29–7.32 (m, 2 H), 7.21–7.25 (m, 3 H), 4.38 (t, J

= 7.2 Hz, 2 H), 3.80 (s, 2 H), 2.97 (t, J = 7.0 Hz, 2 H); 13C NMR (400 MHz, Acetone):

δ = 167.18, 137.26, 128.95, 128.61, 126.78, 66.66, 34.89, 25.84. Ms (EI): m/z = 242.0

[M+H]+ .

(CH2)7

O

O (CH2)15CH3H3C(H2C)7

Cetyl oleate (4x)

1H NMR (400 MHz, Acetone): δ = 5.33–5.39 (m, 2 H), 4.06 (t, J = 6.8 Hz, 2 H), 2.29

(t, J = 7.4 Hz, 2 H), 1.97 – 2.02 (m, 4 H), 1.60–1.61 (m, 4 H), 1.26 – 1.30 (m, 46 H),

0.88 (t, J = 6.8 Hz, 6 H); 13C NMR (400 MHz, Acetone): δ = 173.72, 129.72, 129.48,

64.14, 34.16, 31.68, 29.45, 29.41, 29.36, 29.33, 29.28, 29.23, 29.11, 29.07, 29.01,

28.92, 28.89, 28.42, 26.97, 26.92, 25.70, 24.78, 22.44, 13.84. Ms (EI): m/z =506.5

[M+H]+ .

O

O

Ethyl stearate s18(4y)

1H NMR (400 MHz, Acetone): δ = 4.12 (q, J = 7.2 Hz, 2 H), 2.28 (t, J = 7.6 Hz, 2 H),

1.58–1.63 (m, 2 H), 1.23 – 1.30 (m, 31 H), 0.88 (t, J = 6.8 Hz, 3 H); 13C NMR (400

MHz, Acetone): δ = 173.56, 59.90, 34.23, 31.84, 29.61, 29.52, 29.38, 29.28, 29.19,

29.06, 24.88, 22.59, 14.10, 13.94. Ms (EI): m/z = 312.3 [M+H]+ .

O

O

7 7

Ethyl oleate (4z)

1H NMR (400 MHz, Acetone): δ = 5.33–5.34 (m, 2 H), 4.08-4.13 (m, 2 H), 2.29 (t, J

= 7.6Hz, 2 H), 1.99 – 2.06 (m, 4 H), 1.60 –1.62 (m, 2 H), 1.26 – 1.30 (m, 23 H), 0.88

(t, J = 5.6Hz, 3 H); 13C NMR (400 MHz, Acetone): δ = 173.23, 129.65, 129.43, 59.73,

15 / 67

34.06, 31.74, 29.59, 29.50, 29.36, 29.15, 29.05, 28.94, 27.01, 26.96, 24.76, 22.49,

13.99, 13.83. Ms (EI): m/z = 310.2 [M+H]+ .

OH

O

O

methyl 2-hydroxybenzoate s19(4a’)

1H NMR (400 MHz, CDCl3) δ 10.76 (s, 1H), 7.84 (d, J = 7.9 Hz, 1H), 7.45 (t, J = 7.8

Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 6.88 (t, J = 7.6 Hz, 1H), 3.95 (s, 3H). 13C NMR

(100 MHz, CDCl3) δ 170.60, 161.60, 135.72, 129.91, 119.18, 117.59, 112.39, 52.29.

Ms (EI): m/z = 152.0 [M+H]+ .

O

O

OH

methyl 3-hydroxybenzoate s20(4b’)

1H NMR (400 MHz, CDCl3) δ 7.64 – 7.55 (m, 2H), 7.29 (m, 1H), 7.09 (d, J = 8.0 Hz,

1H), 6.93 (s, 1H), 3.91 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 167.78, 156.13, 131.12,

129.77, 121.77, 120.56, 116.43, 52.50. Ms (EI): m/z = 152.0 [M+H]+ .

O

O

HO

methyl 4-hydroxybenzoate s21(4c’)

1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 6.48

(s, 1H), 3.90 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 167.42, 160.29, 131.97, 122.29,

115.30, 52.10. Ms (EI): m/z = 152.0 [M+H]+ .

O

O

Phenylethyl propionate s27(4d’)

1H NMR (400 MHz, Acetone): δ = 7.20 – 7.29 (m, 5 H), 4.28 (t, J = 7.0 Hz, 2 H),

2.93 (t, J = 7.2 Hz, 2 H), 2.30 (q, J = 7.6 Hz, 2 H), 1.11 (t, J = 7.6 Hz, 3 H); 13C NMR

(400 MHz, Acetone): δ = 174.27, 137.79, 128.80, 128.36, 126.42, 64.67, 35.05, 27.48,

16 / 67

8.99. Ms (EI): m/z =178.1 [M+H]+ .O

O

Br

Bromobutyricacid phenethyl ester (4e’)

1H NMR (400 MHz, Acetone): δ = 7.33 – 7.45 (m, 5 H), 4.43 (t, J = 7.0 Hz, 2 H),

3.51 (t, J = 6.4 Hz, 2 H), 3.06 (t, J = 7.0 Hz, 2 H), 2.58 (t, J = 7.2 Hz, 2 H), 2.20 –

2.27 (m, 2 H); 13C NMR (400 MHz, Acetone): δ = 171.99, 137.46, 128.60, 128.23,

126.31, 64.70, 34.82, 32.44, 32.14, 27.49. Ms (EI): m/z =270.0 [M+H]+ .

O

O

Benzoic acid 2–phenylethyl ester s26(4f’)

1H NMR (400 MHz, Acetone): δ = 8.00–8.02 (m, 2 H), 7.50–7.53 (m, 1 H), 7.38–7.42

(m, 2 H), 7.26–7.32 (m, 4 H), 7.20 – 7.24 (m, 1 H), 4.52 (t, J = 7.0 Hz, 2 H), 3.06 (t, J

= 7.0 Hz, 2 H); 13C NMR (400 MHz, Acetone): δ = 166.37, 137.81, 132.78, 130.22,

129.45, 128.85, 128.43, 128.23, 126.48, 65.35, 35.15. Ms (EI): m/z =226.1 [M+H]+ .

OHO

O

methyl 2-hydroxy-2-phenylacetate s22(6a)

1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 7.4 Hz, 2H), 7.31 (m, 7.2 Hz, 3H), 5.15 (s,

1H), 3.89 (s, 1H), 3.68 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 174.10, 138.38, 128.63,

128.50, 126.68, 72.99, 52.91.. Ms (EI): m/z = 166.1 [M+H]+ .

OOH

O

ethyl 2-hydroxy-2-phenylacetate s22(6b)

1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 7.3 Hz, 2H), 7.33 (dt, J = 17.1, 6.9 Hz, 3H),

5.15 (d, J = 5.6 Hz, 1H), 4.32 – 4.08 (m, 2H), 3.62 (d, J = 5.8 Hz, 1H), 1.24 – 1.17 (m,

17 / 67

3H). 13C NMR (100 MHz, CDCl3) δ 173.68, 138.48, 128.56, 128.39, 126.55, 72.92,

62.20, 14.03. Ms (EI): m/z =180.1 [M+H]+ .

O

O

OH

propyl 2-hydroxy-2-phenylacetate (6c)

1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 7.4 Hz, 2H), 7.38 – 7.30 (m, 3H), 5.16 (d,

J = 4.3 Hz, 1H), 4.16 – 4.08 (m, 2H), 3.58 (d, J = 5.1 Hz, 1H), 1.59 (m, 2H), 0.82 (t, J

= 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 173.81, 138.51, 128.54, 128.38, 126.52,

72.87, 67.70, 21.82, 10.10. Ms (EI): m/z =194.1 [M+H]+ .

O

O

OH

butyl 2-hydroxy-2-phenylacetate s23(6d)

1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 7.5 Hz, 2H), 7.37 – 7.27 (m, 3H), 5.15 (d,

J = 5.5 Hz, 1H), 4.19 – 4.08 (m, 2H), 3.73 (d, J = 5.7 Hz, 1H), 1.53 (m, 2H), 1.22 (m,

2H), 0.84 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 173.78, 138.53, 128.52,

128.36, 126.54, 72.92, 65.96, 30.41, 18.85, 13.54.Ms (EI): m/z =208.1 [M+H]+ .

O

O

OH

hexyl 2-hydroxy-2-phenylacetate s24(6e)

1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 7.6 Hz, 2H), 7.38 – 7.29 (m, 3H), 5.15 (d,

J = 5.7 Hz, 1H), 4.14 (t, J = 6.6 Hz, 2H), 3.61 (d, J = 5.7 Hz, 1H), 1.61 – 1.51 (m, 2H),

1.23 (m, 6H), 0.84 (t, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 173.80, 138.52,

128.53, 128.37, 126.52, 72.89, 66.27, 31.22, 28.36, 25.26, 22.45, 13.93.

Ms (EI): m/z =236.1 [M+H]+ .

OHO

O

isopropyl 2-hydroxy-2-phenylacetate s23(6f)

18 / 67

1H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 7.6 Hz, 2H), 7.23 (m, 3H), 5.03 (d, J = 5.8

Hz, 1H), 4.97 (m, 1H), 3.56 (d, J = 5.9 Hz, 1H), 1.18 (d, J = 6.0 Hz, 3H), 1.01 (d, J =

6.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 173.23, 138.61, 128.49, 128.27, 126.46,

72.94, 70.10, 21.70, 21.39. Ms (EI): m/z =194.1 [M+H]+ .

O

O

OH

isobutyl 2-hydroxy-2-phenylacetate (6g)

1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 7.5 Hz, 2H), 7.38 – 7.29 (m, 3H), 5.17 (d,

J = 5.6 Hz, 1H), 3.93 (m, 2H), 3.60 (d, J = 5.7 Hz, 1H), 1.86 (m, 1H), 0.80 (m, 6H).

13C NMR (100 MHz, CDCl3) δ 173.81, 138.52, 128.51, 128.38, 126.52, 72.86, 72.05,

27.66, 18.77, 18.75.Ms (EI): m/z =208.1 [M+H]+ .

OHO

O

cyclohexyl 2-hydroxy-2-phenylacetate s25(6i)

1H NMR (400 MHz, CDCl3) δ 7.51 – 7.38 (m, 2H), 7.30 (dt, J = 14.0, 7.3 Hz, 3H),

5.13 (d, J = 5.9 Hz, 1H), 4.90 – 4.75 (m, 1H), 3.76 (d, J = 5.9 Hz, 1H), 1.88 – 1.77 (m,

1H), 1.63 (d, J = 16.3 Hz, 2H), 1.54 – 1.40 (m, 3H), 1.31 (ddd, J = 24.6, 14.0, 8.1 Hz,

4H). 13C NMR (100 MHz, CDCl3) δ 173.18, 138.78, 128.44, 128.22, 126.46, 74.60,

72.93, 31.33, 30.96, 25.20, 23.36, 23.15. Ms (EI): m/z =234.1 [M+H]+ .

O

O

OH

allyl 2-hydroxy-2-phenylacetate (6j)

1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 7.0 Hz, 2H), 7.39 – 7.29 (m, 3H), 5.82 (m,

1H), 5.20 (d, J = 4.7 Hz, 2H), 5.16 (d, J = 7.0 Hz, 1H), 4.70 – 4.58 (m, 2H), 3.59 (d, J

= 5.7 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 173.40, 138.27, 131.17, 128.64, 128.53,

126.62, 118.78, 72.94, 66.49. Ms (EI): m/z =192.1 [M+H]+ .

19 / 67

O

O

OH

but-3-yn-1-yl 2-hydroxy-2-phenylacetate (6k)

1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 7.4 Hz, 2H), 7.39 – 7.29 (m, 3H), 5.20 (d,

J = 5.5 Hz, 1H), 4.33 – 4.15 (m, 2H), 3.52 (d, J = 5.8 Hz, 1H), 2.48 (m, 2H), 1.94 (s,

1H). 13C NMR (100 MHz, CDCl3) δ 173.42, 138.12, 128.61, 128.52, 126.59, 79.27,

72.85, 70.30, 63.52, 18.82. Ms (EI): m/z =204.1 [M+H]+ .

O

O

OH

benzyl 2-hydroxy-2-phenylacetate s26(6m)

1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 7.1 Hz, 2H), 7.38 – 7.33 (m, 3H), 7.30 (d,

J = 2.1 Hz, 3H), 7.20 (d, J = 2.8 Hz, 2H), 5.23 (t, J = 8.2 Hz, 2H), 5.14 (d, J = 12.3

Hz, 1H), 3.44 (d, J = 5.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 173.53, 138.17,

134.98, 128.62, 128.58, 128.53, 128.47, 127.96, 126.60, 72.98, 67.70.

Ms (EI): m/z =242.1[M+H]+ .

O

O

OH

phenethyl 2-hydroxy-2-phenylacetate (6n)

1H NMR (400 MHz, CDCl3) δ 7.35 (m, 2H), 7.32 (d, J = 5.4 Hz, 3H), 7.20 (d, J = 6.5

Hz, 3H), 7.01 (d, J = 7.0 Hz, 2H), 5.12 (d, J = 5.6 Hz, 1H), 4.39 – 4.28 (m, 2H), 3.57

(d, J = 5.6 Hz, 1H), 2.90 – 2.78 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 173.64,

138.31, 137.26, 128.89, 128.64, 128.57, 128.47, 126.68, 126.65, 72.94, 66.57, 34.91.

Ms (EI): m/z =256.1 [M+H]+ .

O

O

OH

3-phenylpropyl 2-hydroxy-2-phenylacetate (6o)

1H NMR (400 MHz, CDCl3) δ 7.42 (m, 2H), 7.33 (m, 3H), 7.22 (m, 2H), 7.15 (t, J =

20 / 67

7.2 Hz, 1H), 6.98 (m, 2H), 5.15 (d, J = 5.5 Hz, 1H), 4.12 (t, J = 6.3 Hz, 2H), 3.63 (d, J

= 5.6 Hz, 1H), 2.48 (t, J = 7.6 Hz, 2H), 1.86 (m, 2H). 13C NMR (100 MHz, CDCl3) δ

173.75, 140.78, 138.58, 128.66, 128.53, 128.49, 128.43, 126.63, 126.12, 72.95, 65.25,

31.78, 30.03. Ms (EI): m/z =270.1 [M+H]+ .

O

O

OH

NO2

2-nitrobenzyl 2-hydroxy-2-phenylacetate (6p)

1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 7.7 Hz, 1H), 7.47 (m, 4H), 7.43 – 7.36 (m,

3H), 7.11 (d, J = 7.3 Hz, 1H), 5.69 (d, J = 15.1 Hz, 1H), 5.55 (d, J = 15.1 Hz, 1H),

5.30 (d, J = 5.3 Hz, 1H), 3.46 (d, J = 5.5 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ

173.13, 147.14, 137.92, 133.85, 131.49, 131.07, 128.87, 128.79, 128.26, 126.72,

125.14, 73.05, 64.15. Ms (EI): m/z =287.1 [M+H]+ .

OOH

O

Cyclandelate (6q)

Prepared from mandelic acid (R, 1.0 mmol), 3,3,5-trimethylcyclohexanol (mixture of

R/S, 1.0 mmol) according to general procedure. The crude residue was purified by

short flash column chromatography to yield 7q as a mixture of R/S (0.24g, 87 %). 1H

NMR (400 MHz, CDCl3): δ = 7.40-7.38 (m, 2 H), 7.33-7.29 (m, 3 H), 5.15 (s, 1 H),

5.08-5.09 (m, 1 H), 3.49 (s, 1 H), 2.00-2.02 (m, 0.9 H), 1.90-1.4 (m, 4 H), 1.31-

1.10(m, 4.3 H),0.94-0.82 (m, 9 H), 0.78-0.69 (m, 5H), 0.46 (s, 1.7 H); 13C NMR (400

MHz, CDCl3): δ = 173.27, 138.60, 128.50, 128.27, 126.43, 126.41, 73.56, 72.89,

47.35, 47.33, 43.77, 43.31, 40.18, 39.72, 32.94, 32.88, 32.32, 32.24, 27.06, 26.98,

25.48, 25.41, 22.22, 22.14. Ms (EI): m/z =276.1 [M+H]+ . HRMS calc. for C17H24O3

276.1720, found 276.1728. The 1H NMR and 13C NMR data of the mixture compound

7q are consistent with that of known cyclandelate (R/S) which was purchased from

Energy.

21 / 67

References(s1) R. Qiu, X. Xu, L. Peng, Y. Zhao, N. Li and S. Yin, Chem. Eur. J. 2012, 18, 6172–6182;(s2) D. A, Slack and M. C, Baird, J. Am. Chem. Soc.1976, 98,5339-5346;(s3) O. Noboru; K. Akio; M. Hideyoshi; H. Isami and K. Aritsune, J. Org. Chem. 1985, 50, 3692-3698;(s4) Janza, Birgit and Studer, Armido. J. Org. Chem. 2005, 70, 6991-6994;(s5) M. Silja, E. Melanie, J. Anja and P. Bernd, Org. Lett.2008, 10, 53-56;(s6) M. Silja and P. Bernd, J. Org. Chem. 2010, 75, 3715-3721;(s7) T. Yasuhiro, H. Moritsugu, K. Norihisa, N. Takeshi, S. Kazunori, H. Mamoru and M. Shin-Ichi, J. Heterocycl. Chem. 2000, 37, 1351-1353;(s8) M. Gordon, S. H. Grover and J. B. Stothers, Can. J. Chem. Eng. 1973, 51, 2092-2097;(s9) Q. Liu, Y. Lan, J. Liu, G. Li, Y. Wu and A. Lei, J. Am. Chem. Soc.2009, 131,10201-10210;(s10) S. T. Heller, and R. Sarpong, Org. Lett.2010, 12, 4572-4575;(s11) I. Takanori, M. Yusuke, H. Yukiko, O. Takashi and M. Kazushi, J. Org. Chem. 2008, 73, 5147-5150;(s12) O. Takashi, I. Takanori, M. Yusuke, Y. Asako and M. Kazushi, J. Am. Chem. Soc.2008, 130, 2944-2945;(s13) X. Liu and W. Hu, J. Chem. Res. 2004, 8, 564-565;(s14) B. Cherif, G. David and Y. Miguel, Synthesis. 2006, 319-314;(s15) E. H. White, M. Ribi, L.K. Cho, N. Egger, P. M. Dzadzic and, M. J. Todd, J. Org. Chem. 1984, 49,4866-4871;(s16) A. Thierry, L. Aymeric, G. Yves, C. Herve, G. Laurent, T. Alphonse and B. Gerard, Angew. Chem. Int. Ed. 2011, 50,3552–3556;(s17) M. Silja and P. Bernd, J. Org. Chem. 2010, 75, 3715-3721;(s18) S. Masumi and S. Takeshi, B. Chem. Soc. Jpn. 2004, 77, 1217-1227;(s19) S. Huang, I. Hsei and C. Chen, Bioorg. Med. Chem. 2006, 14, 6106-6119;(s20) B. Raymond and M. Gabriel, Org. Lett.2002, 4, 2013-2016;(s21) Y. C. Chang, F. R. Chang and Y. C. Wu, J. Chin. Inst. Chem.. Soc.2000, 47, 373-380;(s22) A. R. Katritzky, S. K. Singh, C. Cai and S. Bobrov, J. Org. Chem. 2006, 71, 3364-3374;(s23) M. Toshikatsu, I. Kazuaki and Y. Hisashi, Org. Lett.2005, 7, 5047-5050;(s24) D. Debapratim, R. Sangita and D. P. Kumar, Org. Lett.2004, 6, 4133-4136;(s25) H. E. Bartrum, D. C. Blakemore, C. J. Moody and C. J. Hayes, Chem. Eur. J. 2011, 17, 9586-9589;(s26) C. T. Chen and Y. S. Munot, J. Org. Chem. 2005, 70, 8625-8627;(s27) J. McNulty, J. J. Nair, S. Cheekoori, V. Larichev, A. Capretta and A. J. Robertson, Chem. Eur. J. 2006, 12, 9314-9322;

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S6. NMR spectra of all compoundsO

O

Acetic acid 2–phenylethyl ester (4a)

23 / 67

O

O

Acetic acid 3–phenylpropyl ester (4b)

24 / 67

O

O

Acetic acid benzyl ester (4c)

25 / 67

O

O

Phenyl acetate (4d)

26 / 67

O

O

Benzhydryl acetate (4e)

27 / 67

O

O

cyclohexyl acetate (4f)

28 / 67

O

O

O

O

propane-1,3-diyl diacetate (4g)

29 / 67

O

O

methyl cyclopentanecarboxylate (4i)

30 / 67

O

O

Methyl oleate (4j)

31 / 67

O

O

methyl benzoate (4k)

32 / 67

O

OS

Br

methyl 5-bromotetrahydrothiophene-2-carboxylate (4l)

33 / 67

O

O

Butyl benzoate (4m)

34 / 67

O

O

Hexyl benzoate (4n)

35 / 67

O

O

n-Heptyl benzoate (4o)

36 / 67

O

O

n-Decyl benzoate (4p)

37 / 67

O

O

HO

n-Decyl 4-hydroxybenzoate (4q)

38 / 67

O

O

Isobutyl benzoate (4r)

39 / 67

O

O

Prop-2-yn-1-yl benzoate (4t)

40 / 67

O

O

10–Undecenic acid 2–phenylethylester (4u)

41 / 67

O

O

Phenylethyl acrylate (4v)

42 / 67

OBr

O

Bromoacetic acid 2–phenylethyl ester (4w)

43 / 67

(CH2)7

O

O (CH2)15CH3H3C(H2C)7

Cetyl oleate (4x)

44 / 67

O

O

Ethyl stearate (4y)

45 / 67

O

O

7 7

Ethyl oleate (4z)

46 / 67

OH

O

O

methyl 2-hydroxybenzoate (4a’)

47 / 67

O

O

OH

methyl 3-hydroxybenzoate (4b’)

48 / 67

O

O

HO

methyl 4-hydroxybenzoate (4c’)

49 / 67

O

O

Phenylethyl propionate (4d’)

50 / 67

O

O

Br

Bromobutyricacid phenethyl ester (4e’)

51 / 67

O

O

Benzoic acid 2–phenylethyl ester (4f’)

52 / 67

OHO

O

methyl 2-hydroxy-2-phenylacetate (6a)

53 / 67

OOH

O

ethyl 2-hydroxy-2-phenylacetate (6b)

54 / 67

O

O

OH

propyl 2-hydroxy-2-phenylacetate (6c)

55 / 67

O

O

OH

butyl 2-hydroxy-2-phenylacetate (6d)

56 / 67

O

O

OH

hexyl 2-hydroxy-2-phenylacetate (6e)

57 / 67

OHO

O

isopropyl 2-hydroxy-2-phenylacetate (6f)

58 / 67

O

O

OH

isobutyl 2-hydroxy-2-phenylacetate (6g)

59 / 67

OHO

O

cyclohexyl 2-hydroxy-2-phenylacetate (6i)

60 / 67

O

O

OH

allyl 2-hydroxy-2-phenylacetate (6j)

61 / 67

O

O

OH

but-3-yn-1-yl 2-hydroxy-2-phenylacetate (6k)

62 / 67

O

O

OH

benzyl 2-hydroxy-2-phenylacetate (6m)

63 / 67

O

O

OH

phenethyl 2-hydroxy-2-phenylacetate (6n)

64 / 67

O

O

OH

3-phenylpropyl 2-hydroxy-2-phenylacetate (6o)

65 / 67

O

O

OH

NO2

2-nitrobenzyl 2-hydroxy-2-phenylacetate (6p)

66 / 67

OOH

O

Cyclandelate (6q)

67 / 67

Cyclandelate (R/S) which was purchased from Energy.