Supporting Information. Zirconocene-Catalyzed Direct (trans)esterification of Acyl. Acids(Esters) and Alcohols in a Strict 1:1 Ratio under

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1 Electronic Supplementary Material (ESI) for Green Chemistry. This journal is The Royal Society of Chemistry 207 Supporting Information Zirconocene-Catalyzed Direct (trans)esterification of Acyl Acids(Esters) and Alcohols in a Strict : Ratio under Solvent-Free Conditions Zhi Tang, a Qiutao Jiang, b Lifen Peng, a Xinhua Xu, a* Jie Li, b* Renhua Qiu a* and Chak-Tong Au, c a State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 40082, China; b College of Chemistry and Chemical Engineering, Central South University, Changsha, China, c Hunan Institute of Engineering, Xiangtan, P.R. China Correspondence to: renhuaqiu@hnu.edu.cn (R. Q.), xhx58@hnu.edu.cn (X. X), @qq.com Fax: List of contents S0 General method S2 S X-Ray and TG-DSC analysis of comlex Cp 2 Zr(pf) 2 S2 S2 H NMR spectra and 9 F NMR spectra of the fresh catalyst S4 S3 H NMR spectra of the recycled catalyst S5 S4 Experimental section S6 S5 H NMR spectra and 3 C NMR spectra data of all compounds S8 S6 NMR spectra of all compounds S2 / 67

2 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 CaH 2. The NMR spectra were recorded at 25 C on INVA-400M (USA) calibrated with tetramethylsilane (TMS) as an internal reference. Elemental analyses were performed by VARI EL III. TG-DSC analysis was performed on a HCT- (HENVEN, Beijing, China) instrument. X-ray single crystal diffraction analysis was performed using the SMART-APEX and RASA-7A equipment at Shanghai Institute rganic 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. S. X-Ray and TG-DSC anaylsis of complex Cp 2 Zr(Pf) 2 s C 30 H 24 F 34 0 S 2 Zr, Prismatic, colorless, M r = , D x =.905 Mg m 3, Triclinic, P, a = (3) Å, b =.955 (6) Å, c = (3) Å, α = (3), β = (3), γ = (3), V = (5) Å 3, Z = 2, θ = , mm,t = 293 (2) K, measured reflections/independent reflections 2436/8583, R int = 0.04, h = 2-,k = 4-, l = 24-22, R = 0.095,wR 2 = 0.277, S = 0.95.CCDC No / 67

3 Figure S. RTEP representative of X-ray structure of catalyst 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 Cp 2 Zr(H 2 ) 3 (S 2 C 8 F 7 ) 2 THF. 3 / 67

4 S2. H NMR spectra and 9 F NMR spectra of the fresh catalyst Catalyst H NMR (400 MHz, Acetone): δ = 6.76 (s, 0 H, CpH), 3.63 (t, J = 5.6 Hz, 4 H, THF), (m, 4 H, THF); 9 F NMR (376 MHz; Acetone): δ = (t, J = 9.8 Hz, 3 F, CF 3 ), (s, 2 F, CF 2 ), (s, 2 F, CF 2 ), (m, 6 F, (CF 2 ) 3 ), (s, 2 F, CF 2 ), (m, 2 F, CF 2 ). Figure S3 H NMR spectra of the fresh catalyst 4 / 67

5 Figure S4 9 F NMR spectra of the fresh catalyst 5 / 67

6 S3. H 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 CH 2 Cl 2 for the next cycle. recycled catalyst H NMR (400 MHz, Acetone): δ = 6.76 (s, 0 H, CpH), 6 / 67

7 S4. Experimental Section Preparation of Cp 2 Zr(H 2 ) 3 (S 2 C 8 F 7 ) 2 THF () s To a solution of Cp 2 ZrCl 2 (292 mg, 0.99 mmol) in THF (20 ml) was added a solution of AgS 2 C 8 F 7 (.2 g, 2.0 mmol) in THF (0 ml). The mixture was stirred in the dark at 25 C for 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 THF(794 mg, 65%): M.p C. H NMR (400 MHz, Acetone-d 6 ): δ = 6.76 (s, 0 H, CpH), 3.63 (t, J = 5.6 Hz, 4 H, THF), (m, 4 H, THF); 9F NMR (376 MHz; Acetone): δ = (t, J = 9.8 Hz, 3 F, CF3 ), (s, 2 F, CF2 ), (s, 2 F, CF2 ), (m, 6 F, (CF2)3 ), (s, 2 F, CF2 ), (m, 2 F, CF2 ). Elemental analysis for Cp 2 Zr(S 2 C 8 F 7 ) 2 after pumping for a week: calcd. (%) for C 26 H 0 F 34 6 S 2 Zr: C, 25.60; H, 0.83; found: C, 25.67; H, Elemental analysis for Cp 2 Zr(S 2 C 8 F 7 ) 2 4H 2 after standing in open air for 2 days: calcd (%) for C 26 H 8 F 34 0 S 2 Zr: C, 24.8; H,.40; found: C, 24.34; H,.33. C 30 H 24 F 34 0 S 2 Zr, Prismatic, colorless, Mr = , Dx =.905 Mg m 3, Triclinic, P, a = (3) Å, b =.955 (6) Å, c = (3) Å, α = (3), β = (3), γ = (3), V = (5) Å3, Z = 2, θ = , mm,t = 293 (2) K, measured reflections/independent reflections 2436/8583, Rint = 0.04, h = 2-,k = 4-, l = 24-22, R = 0.095,wR2 = 0.277, S = 0.95.CCDC No Typical procedure for direct esterification of alcohol with carboxylic acid using catalyst. To a round-bottom flask was added 2-phenylethanol (22 mg,.0 mmol) and equivalent of acetic acid (60 mg,.0 mmol) and catalyst (2.6 mg, 0.0 mmol,.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 (0 ml 3). By means of filtration, the catalyst was separated and used for the next cycle, and the filtrate was washed twice with 0 ml of saturated brine, and extracted by petroleum ether (0 ml 2). Subsequently the portions of petroleum ether were combined together, dried by sodium sulfate, and evaporated to obtain the crude ester. Finally, 7 / 67

8 the ester was subject to short flash column chromatography on silica gel (petroleum ether: ethyl acetate = 8:, Rf = 0.7) to afford the colorless liquid, 62 mg, yield, 99%. Typical procedure for transesterification of alcohol with carboxylic acid using catalyst. To a round-bottom flask was added 2-phenylethanol (22 mg,.0 mmol) and equivalent of methyl propionate (88 mg,.0 mmol) and catalyst (2.6 mg, 0.0 mmol,.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 (0 ml 3). By means of filtration, the catalyst was separated and used for the next cycle, and the filtrate was washed twice with 0 ml of saturated brine, and extracted by petroleum ether (0 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:, Rf = 0.7) to afford the colorless liquid, 60 mg, yield, 90%. S5. H NMR and 3 C NMR Spectral Data of All Compounds 8 / 67

9 Acetic acid 2 phenylethyl ester s2 (4a) H NMR (400 MHz, Acetone): δ = (m, 5 H), 4.26 (t, J = 7.2 Hz, 2 H), 2.90 (t, J = 7.0 Hz, 2 H),.99 (s, 3 H); 3 C NMR (400 MHz, Acetone): δ = 70.67, 37.62, 28.66, 28.27, 26.33, 64.68, 34.88, Ms (EI): m/z = 64. [M+H] +. Acetic acid 3 phenylpropyl ester s3 (4b) H NMR (400 MHz, Acetone): δ = (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), (m, 2 H); 3 C NMR (400 MHz, Acetone): δ =7.5, 4.22, 28.45, 28.40, 26.02, 63.84, 32.9, 30.9, Ms (EI): m/z = 78. [M+H] +. Acetic acid benzyl ester s4 (4c) H NMR (400 MHz, Acetone): δ = (m, 5 H), 5.0 (s, 2 H), 2.09 (s, 3 H); 3 C NMR (400 MHz, Acetone): δ = 70.75, 35.86, 28.46, 28.5, 66.20, Ms (EI): m/z = 50. [M+H] +. Phenyl acetate s5 (4d) H NMR (400 MHz, Acetone): δ = (m, 2 H), (m, H), (m, 2 H), 2.25 (s, 3 H); 3 C NMR (400 MHz, Acetone): δ = 69.24, 50.60, 29.25, 25.64, 2.42, 20.92, Ms (EI): m/z = 36. [M+H] +. 9 / 67

10 Benzhydryl acetate s6 (4e) H NMR (400 MHz, CDCl3) δ (m, 0H), 6.8 (s, H), 2.07 (s, 3H); 3C NMR (00 MHz, CDCl3) δ 70.03, 40.25, 28.53, 27.93, 27.3, 76.75, Ms (EI): m/z = 226. [M+H] +. cyclohexyl acetate s6 (4f) H NMR (400 MHz, CDCl 3 ) δ (m, H), 2.00 (s, 3H),.82 (d, J = 0.3 Hz, 2H),.70 (m, 2H), (m, H),.37 (m, 4H),.23 (m, H). 3 C NMR (00 MHz, CDCl 3 ) δ 70.56, 72.65, 3.63, 25.36, 23.78, Ms (EI): m/z = 42. [M+H] +. propane-,3-diyl diacetate s7 (4g) H NMR (400 MHz, CDCl 3 ) δ 4.0 (t, J = 6.3 Hz, 4H), 2.00 (s, 6H), (m, 2H). 3 C NMR (00 MHz, CDCl 3 ) δ 70.93, 60.98, 27.85, Ms (EI): m/z = 60. [M+H] +. methyl cyclopentanecarboxylate s8 (4i) H NMR (400 MHz, CDCl 3 ) δ 3.63 (s, 3H), 2.69 (m, H),.84 (m, 2H),.80.6 (m, 4H),.53 (m, 2H). 3 C NMR (00 MHz, CDCl 3 ) δ 77.2, 5.49, 43.65, 29.97, Ms (EI): m/z = 28. [M+H] +. 0 / 67

11 Methyl oleate (4j) H NMR (400 MHz, Acetone): δ = (m, 2 H), 3.65 (s, 3 H), (m, 2 H), (m, 4 H), (m, 2 H), (m, 20 H), 0.88 (t, J = 6.8 Hz, 3 H); 3 C NMR (400 MHz, Acetone): δ = 74.00, 29.8, 29.57, 5.8, 29.57, 29.43, 29.22, 29.05, 29.03, 27.08, 27.05, 24.84, 22.57, Ms (EI): m/z = [M+H] +. methyl benzoate s9 (4k) H NMR (400 MHz, CDCl 3 ) δ 8.04 (d, J = 7.8 Hz, 2H), 7.55 (d, J = 7.5 Hz, H), 7.44 (t, J = 7.6 Hz, 2H), 3.92 (s, 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 67.4, 32.92, 30.6, 29.58, 28.37, Ms (EI): m/z = 36. [M+H] +. Br S methyl 5-bromotetrahydrothiophene-2-carboxylate s0 (4l) H NMR (400 MHz, CDCl 3 ) δ 7.47 (d, J = 3.9 Hz, H), 7.00 (d, J = 3.9 Hz, H), 3.80 (s, 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 6.57, 34.66, 33.70, 30.90, 20.26, Ms (EI): m/z = 29. [M+H] +. Butyl benzoate s (4m) H NMR (400 MHz, Acetone): δ = 8.05 (d, J = 7.6 Hz, 2 H), (m, H), (m, 2 H), 4.33 (t, J = 6.6 Hz, 2 H), (m, 2 H), (m, 2 H), 0.98 (t, J = 7.4 Hz, 3 H); 3 C NMR (400 MHz, Acetone): δ = 66.69, 32.78, 30.55, 29.53, 28.3, 64.83, 30.79, 9.28, Ms (EI): m/z = 78. [M+H] +. / 67

12 Hexyl benzoate s2 (4n) H NMR (400 MHz, Acetone): δ = (m, 2 H), (m, H), (m, 2 H), 4.3 (t, J = 6.8 Hz, 2 H), (m, 2 H), (m, 2 H), (m, 4 H), 0.90 (t, J = 6.8 Hz, 3 H); 3 C NMR (400 MHz, Acetone): δ = 66.68, 32.77, 30.57, 29.53, 28.3, 65.2, 3.48, 28.70, 25.72, 22.56, Ms (EI): m/z = 206. [M+H] +. n-heptyl benzoate s3 (4o) H NMR (400 MHz, Acetone): δ = (m, 2 H), (m, H), (m, 2 H), 4.30 (t, J = 6.8 Hz, 2 H),.7.78 (m, 2 H), (m, 8 H), 0.89 (t, J = 7.0 Hz, 3 H); 3 C NMR (400 MHz, Acetone): δ = 66.29, 32.49, 30.38, 29.30, 28.04, 64.83, 3.55, 28.78, 28.56, 25.83, 22.40, Ms (EI): m/z = 220. [M+H] +. n-decyl benzoate s4 (4p) H NMR (400 MHz, Acetone): δ = (m, 2 H), (m, H), (m, 2 H), 4.38 (t, J = 6.6 Hz, 2 H), (m, 2 H), (m, 4 H), 0.96 (t, J = 6.6 Hz, 3 H); 3 C NMR (400 MHz, Acetone): δ = 66.34, 32.52, 30.42, 29.35, 28.08, 64.89, 3.76, 29.40, 29.7, 29.6, 28.60, 25.9, 22.53, Ms (EI): m/z = 262. [M+H] +. H n-decyl 4-hydroxybenzoate (4q) H 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, H), 4.28 (t, J = 6.6 Hz, 2 H), (m, 2 H), (m, 4 H), 0.88 (t, J = 6.8 Hz, 3 H); 3 C NMR (400 MHz, Acetone): δ = 66.92, 6.9, 3.70, 2.86, 5.8, 64.83, 3.86, 29.58, 29.53, 29.40, 29.28, 25.7, 22.63, Ms (EI): m/z =278. [M+H] +. 2 / 67

13 Isobutyl benzoate s5 (4r) H NMR (400 MHz, Acetone): δ = 8.06 (d, J = 7.2 Hz, 2 H), 7.54 (t, J = 7.4 Hz, H), (m, 2 H), 4. (d, J = 6.4 Hz, 2 H), (m, H),.02 (d, J = 6.8 Hz, 6 H); 3 C NMR (400 MHz, Acetone): δ = 66.47, 32.68, 30.44, 29.42, 28.2, 70.87, 27.82, Ms (EI): m/z = 78.2 [M+H] +. Prop-2-yn--yl benzoate s6( 4t) H NMR (400 MHz, Acetone): δ = 8.08 (d, J = 7.6 Hz, 2 H), 7.59 (t, J = 7.4 Hz, H), 7.46 (t, J = 7.6 Hz, 2 H), 4.93 (s, 2 H), (m, H); 3 C NMR (400 MHz, Acetone): δ = 65.84, 33.38, 29.83, 29.39, 28.47, 77.74, 75.03, Ms (EI): m/z = 60. [M+H] +. 0 Undecenic acid 2 phenylethylester s7 (4u) H NMR (400 MHz, Acetone): δ = (m, 2 H), (m, 3 H), (m, H), (m, H), (m, 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 = 4.4, 7.2 Hz, 2 H), (m, 2 H), (m, 0 H); 3 C NMR (400 MHz, Acetone): δ = 73.57, 39.06, 37.93, 28.9, 28.48, 26.54, 4.25, 64.68, 35.22, 34.30, 33.85, 29.34, 29.27, 29.4, 29.2, 28.96, Ms (EI): m/z = [M+H] +. Phenylethyl acrylate (4v) H NMR (400 MHz, Acetone): δ = (m, 2 H), (m, 3 H), 6.38 (m, H), 6. (m, H), 5.8 (m, H), 4.37 (t, J = 7.2 Hz, 2 H), 2.98 (t, J = 7.2 Hz, 2 H); 3 C NMR (400 MHz, Acetone): δ = 66.06, 37.74, 30.63, 28.86, 28.46, 26.53, 3 / 67

14 64.96, Ms (EI): m/z = 76. [M+H] +. Br Bromoacetic acid 2 phenylethyl ester (4w) H NMR (400 MHz, Acetone): δ = (m, 2 H), (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); 3 C NMR (400 MHz, Acetone): δ = 67.8, 37.26, 28.95, 28.6, 26.78, 66.66, 34.89, Ms (EI): m/z = [M+H] +. H 3 C(H 2 C) 7 (CH 2 ) 7 (CH 2 ) 5 CH 3 Cetyl oleate (4x) H NMR (400 MHz, Acetone): δ = (m, 2 H), 4.06 (t, J = 6.8 Hz, 2 H), 2.29 (t, J = 7.4 Hz, 2 H), (m, 4 H),.60.6 (m, 4 H), (m, 46 H), 0.88 (t, J = 6.8 Hz, 6 H); 3 C NMR (400 MHz, Acetone): δ = 73.72, 29.72, 29.48, 64.4, 34.6, 3.68, 29.45, 29.4, 29.36, 29.33, 29.28, 29.23, 29., 29.07, 29.0, 28.92, 28.89, 28.42, 26.97, 26.92, 25.70, 24.78, 22.44, Ms (EI): m/z =506.5 [M+H] +. Ethyl stearate s8 (4y) H NMR (400 MHz, Acetone): δ = 4.2 (q, J = 7.2 Hz, 2 H), 2.28 (t, J = 7.6 Hz, 2 H), (m, 2 H), (m, 3 H), 0.88 (t, J = 6.8 Hz, 3 H); 3 C NMR (400 MHz, Acetone): δ = 73.56, 59.90, 34.23, 3.84, 29.6, 29.52, 29.38, 29.28, 29.9, 29.06, 24.88, 22.59, 4.0, Ms (EI): m/z = 32.3 [M+H] Ethyl oleate (4z) H NMR (400 MHz, Acetone): δ = (m, 2 H), (m, 2 H), 2.29 (t, J = 7.6Hz, 2 H), (m, 4 H), (m, 2 H), (m, 23 H), 0.88 (t, J = 5.6Hz, 3 H); 3 C NMR (400 MHz, Acetone): δ = 73.23, 29.65, 29.43, 59.73, 4 / 67

15 34.06, 3.74, 29.59, 29.50, 29.36, 29.5, 29.05, 28.94, 27.0, 26.96, 24.76, 22.49, 3.99, Ms (EI): m/z = 30.2 [M+H] +. H methyl 2-hydroxybenzoate s9 (4a ) H NMR (400 MHz, CDCl 3 ) δ 0.76 (s, H), 7.84 (d, J = 7.9 Hz, H), 7.45 (t, J = 7.8 Hz, H), 6.98 (d, J = 8.4 Hz, H), 6.88 (t, J = 7.6 Hz, H), 3.95 (s, 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 70.60, 6.60, 35.72, 29.9, 9.8, 7.59, 2.39, Ms (EI): m/z = 52.0 [M+H] +. H methyl 3-hydroxybenzoate s20 (4b ) H NMR (400 MHz, CDCl 3 ) δ (m, 2H), 7.29 (m, H), 7.09 (d, J = 8.0 Hz, H), 6.93 (s, H), 3.9 (s, 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 67.78, 56.3, 3.2, 29.77, 2.77, 20.56, 6.43, Ms (EI): m/z = 52.0 [M+H] +. H methyl 4-hydroxybenzoate s2 (4c ) H NMR (400 MHz, CDCl 3 ) δ 7.95 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 6.48 (s, H), 3.90 (s, 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 67.42, 60.29, 3.97, 22.29, 5.30, Ms (EI): m/z = 52.0 [M+H] +. Phenylethyl propionate s27 (4d ) H NMR (400 MHz, Acetone): δ = (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),. (t, J = 7.6 Hz, 3 H); 3 C NMR (400 MHz, Acetone): δ = 74.27, 37.79, 28.80, 28.36, 26.42, 64.67, 35.05, 27.48, 5 / 67

16 8.99. Ms (EI): m/z =78. [M+H] +. Br Bromobutyricacid phenethyl ester (4e ) H NMR (400 MHz, Acetone): δ = (m, 5 H), 4.43 (t, J = 7.0 Hz, 2 H), 3.5 (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), (m, 2 H); 3 C NMR (400 MHz, Acetone): δ = 7.99, 37.46, 28.60, 28.23, 26.3, 64.70, 34.82, 32.44, 32.4, Ms (EI): m/z =270.0 [M+H] +. Benzoic acid 2 phenylethyl ester s26 (4f ) H NMR (400 MHz, Acetone): δ = (m, 2 H), (m, H), (m, 2 H), (m, 4 H), (m, H), 4.52 (t, J = 7.0 Hz, 2 H), 3.06 (t, J = 7.0 Hz, 2 H); 3 C NMR (400 MHz, Acetone): δ = 66.37, 37.8, 32.78, 30.22, 29.45, 28.85, 28.43, 28.23, 26.48, 65.35, Ms (EI): m/z =226. [M+H] +. H methyl 2-hydroxy-2-phenylacetate s22 (6a) H NMR (400 MHz, CDCl 3 ) δ 7.39 (d, J = 7.4 Hz, 2H), 7.3 (m, 7.2 Hz, 3H), 5.5 (s, H), 3.89 (s, H), 3.68 (s, 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 74.0, 38.38, 28.63, 28.50, 26.68, 72.99, Ms (EI): m/z = 66. [M+H] +. H ethyl 2-hydroxy-2-phenylacetate s22 (6b) H NMR (400 MHz, CDCl 3 ) δ 7.42 (d, J = 7.3 Hz, 2H), 7.33 (dt, J = 7., 6.9 Hz, 3H), 5.5 (d, J = 5.6 Hz, H), (m, 2H), 3.62 (d, J = 5.8 Hz, H),.24.7 (m, 6 / 67

17 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.68, 38.48, 28.56, 28.39, 26.55, 72.92, 62.20, Ms (EI): m/z =80. [M+H] +. H propyl 2-hydroxy-2-phenylacetate (6c) H NMR (400 MHz, CDCl 3 ) δ 7.42 (d, J = 7.4 Hz, 2H), (m, 3H), 5.6 (d, J = 4.3 Hz, H), (m, 2H), 3.58 (d, J = 5. Hz, H),.59 (m, 2H), 0.82 (t, J = 7.4 Hz, 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.8, 38.5, 28.54, 28.38, 26.52, 72.87, 67.70, 2.82, 0.0. Ms (EI): m/z =94. [M+H] +. H butyl 2-hydroxy-2-phenylacetate s23 (6d) H NMR (400 MHz, CDCl 3 ) δ 7.4 (d, J = 7.5 Hz, 2H), (m, 3H), 5.5 (d, J = 5.5 Hz, H), (m, 2H), 3.73 (d, J = 5.7 Hz, H),.53 (m, 2H),.22 (m, 2H), 0.84 (t, J = 7.4 Hz, 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.78, 38.53, 28.52, 28.36, 26.54, 72.92, 65.96, 30.4, 8.85, 3.54.Ms (EI): m/z =208. [M+H] +. H hexyl 2-hydroxy-2-phenylacetate s24 (6e) H NMR (400 MHz, CDCl 3 ) δ 7.42 (d, J = 7.6 Hz, 2H), (m, 3H), 5.5 (d, J = 5.7 Hz, H), 4.4 (t, J = 6.6 Hz, 2H), 3.6 (d, J = 5.7 Hz, H),.6.5 (m, 2H),.23 (m, 6H), 0.84 (t, J = 6.6 Hz, 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.80, 38.52, 28.53, 28.37, 26.52, 72.89, 66.27, 3.22, 28.36, 25.26, 22.45, Ms (EI): m/z =236. [M+H] +. H isopropyl 2-hydroxy-2-phenylacetate s23 (6f) 7 / 67

18 H NMR (400 MHz, CDCl 3 ) δ 7.33 (d, J = 7.6 Hz, 2H), 7.23 (m, 3H), 5.03 (d, J = 5.8 Hz, H), 4.97 (m, H), 3.56 (d, J = 5.9 Hz, H),.8 (d, J = 6.0 Hz, 3H),.0 (d, J = 6.2 Hz, 3H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.23, 38.6, 28.49, 28.27, 26.46, 72.94, 70.0, 2.70, Ms (EI): m/z =94. [M+H] +. H isobutyl 2-hydroxy-2-phenylacetate (6g) H NMR (400 MHz, CDCl 3 ) δ 7.43 (d, J = 7.5 Hz, 2H), (m, 3H), 5.7 (d, J = 5.6 Hz, H), 3.93 (m, 2H), 3.60 (d, J = 5.7 Hz, H),.86 (m, H), 0.80 (m, 6H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.8, 38.52, 28.5, 28.38, 26.52, 72.86, 72.05, 27.66, 8.77, 8.75.Ms (EI): m/z =208. [M+H] +. H cyclohexyl 2-hydroxy-2-phenylacetate s25 (6i) H NMR (400 MHz, CDCl 3 ) δ (m, 2H), 7.30 (dt, J = 4.0, 7.3 Hz, 3H), 5.3 (d, J = 5.9 Hz, H), (m, H), 3.76 (d, J = 5.9 Hz, H), (m, H),.63 (d, J = 6.3 Hz, 2H), (m, 3H),.3 (ddd, J = 24.6, 4.0, 8. Hz, 4H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.8, 38.78, 28.44, 28.22, 26.46, 74.60, 72.93, 3.33, 30.96, 25.20, 23.36, Ms (EI): m/z =234. [M+H] +. H allyl 2-hydroxy-2-phenylacetate (6j) H NMR (400 MHz, CDCl 3 ) δ 7.43 (d, J = 7.0 Hz, 2H), (m, 3H), 5.82 (m, H), 5.20 (d, J = 4.7 Hz, 2H), 5.6 (d, J = 7.0 Hz, H), (m, 2H), 3.59 (d, J = 5.7 Hz, H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.40, 38.27, 3.7, 28.64, 28.53, 26.62, 8.78, 72.94, Ms (EI): m/z =92. [M+H] +. 8 / 67

19 H but-3-yn--yl 2-hydroxy-2-phenylacetate (6k) H NMR (400 MHz, CDCl 3 ) δ 7.43 (d, J = 7.4 Hz, 2H), (m, 3H), 5.20 (d, J = 5.5 Hz, H), (m, 2H), 3.52 (d, J = 5.8 Hz, H), 2.48 (m, 2H),.94 (s, H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.42, 38.2, 28.6, 28.52, 26.59, 79.27, 72.85, 70.30, 63.52, Ms (EI): m/z =204. [M+H] +. H benzyl 2-hydroxy-2-phenylacetate s26 (6m) H NMR (400 MHz, CDCl 3 ) δ 7.4 (d, J = 7. Hz, 2H), (m, 3H), 7.30 (d, J = 2. Hz, 3H), 7.20 (d, J = 2.8 Hz, 2H), 5.23 (t, J = 8.2 Hz, 2H), 5.4 (d, J = 2.3 Hz, H), 3.44 (d, J = 5.8 Hz, H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.53, 38.7, 34.98, 28.62, 28.58, 28.53, 28.47, 27.96, 26.60, 72.98, Ms (EI): m/z =242.[M+H] +. H phenethyl 2-hydroxy-2-phenylacetate (6n) H NMR (400 MHz, CDCl 3 ) δ 7.35 (m, 2H), 7.32 (d, J = 5.4 Hz, 3H), 7.20 (d, J = 6.5 Hz, 3H), 7.0 (d, J = 7.0 Hz, 2H), 5.2 (d, J = 5.6 Hz, H), (m, 2H), 3.57 (d, J = 5.6 Hz, H), (m, 2H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.64, 38.3, 37.26, 28.89, 28.64, 28.57, 28.47, 26.68, 26.65, 72.94, 66.57, Ms (EI): m/z =256. [M+H] +. H 3-phenylpropyl 2-hydroxy-2-phenylacetate (6o) H NMR (400 MHz, CDCl 3 ) δ 7.42 (m, 2H), 7.33 (m, 3H), 7.22 (m, 2H), 7.5 (t, J = 9 / 67

20 7.2 Hz, H), 6.98 (m, 2H), 5.5 (d, J = 5.5 Hz, H), 4.2 (t, J = 6.3 Hz, 2H), 3.63 (d, J = 5.6 Hz, H), 2.48 (t, J = 7.6 Hz, 2H),.86 (m, 2H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.75, 40.78, 38.58, 28.66, 28.53, 28.49, 28.43, 26.63, 26.2, 72.95, 65.25, 3.78, Ms (EI): m/z =270. [M+H] +. H N 2 2-nitrobenzyl 2-hydroxy-2-phenylacetate (6p) H NMR (400 MHz, CDCl 3 ) δ 8.09 (d, J = 7.7 Hz, H), 7.47 (m, 4H), (m, 3H), 7. (d, J = 7.3 Hz, H), 5.69 (d, J = 5. Hz, H), 5.55 (d, J = 5. Hz, H), 5.30 (d, J = 5.3 Hz, H), 3.46 (d, J = 5.5 Hz, H). 3 C NMR (00 MHz, CDCl 3 ) δ 73.3, 47.4, 37.92, 33.85, 3.49, 3.07, 28.87, 28.79, 28.26, 26.72, 25.4, 73.05, Ms (EI): m/z =287. [M+H] +. H Cyclandelate (6q) Prepared from mandelic acid (R,.0 mmol), 3,3,5-trimethylcyclohexanol (mixture of R/S,.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 %). H NMR (400 MHz, CDCl 3 ): δ = (m, 2 H), (m, 3 H), 5.5 (s, H), (m, H), 3.49 (s, H), (m, 0.9 H), (m, 4 H),.3-.0(m, 4.3 H), (m, 9 H), (m, 5H), 0.46 (s,.7 H); 3C NMR (400 MHz, CDCl3): δ = 73.27, 38.60, 28.50, 28.27, 26.43, 26.4, 73.56, 72.89, 47.35, 47.33, 43.77, 43.3, 40.8, 39.72, 32.94, 32.88, 32.32, 32.24, 27.06, 26.98, 25.48, 25.4, 22.22, Ms (EI): m/z =276. [M+H]+. HRMS calc. for C 7 H , found The H NMR and 3 C NMR data of the mixture compound 7q are consistent with that of known cyclandelate (R/S) which was purchased from Energy. 20 / 67

21 References (s) R. Qiu, X. Xu, L. Peng, Y. Zhao, N. Li and S. Yin, Chem. Eur. J. 202, 8, ; (s2) D. A, Slack and M. C, Baird, J. Am. Chem. Soc.976, 98, ; (s3). Noboru; K. Akio; M. Hideyoshi; H. Isami and K. Aritsune, J. rg. Chem. 985, 50, ; (s4) Janza, Birgit and Studer, Armido. J. rg. Chem. 2005, 70, ; (s5) M. Silja, E. Melanie, J. Anja and P. Bernd, rg. Lett.2008, 0, 53-56; (s6) M. Silja and P. Bernd, J. rg. Chem. 200, 75, ; (s7) T. Yasuhiro, H. Moritsugu, K. Norihisa, N. Takeshi, S. Kazunori, H. Mamoru and M. Shin-Ichi, J. Heterocycl. Chem. 2000, 37, ; (s8) M. Gordon, S. H. Grover and J. B. Stothers, Can. J. Chem. Eng. 973, 5, ; (s9) Q. Liu, Y. Lan, J. Liu, G. Li, Y. Wu and A. Lei, J. Am. Chem. Soc.2009, 3, ; (s0) S. T. Heller, and R. Sarpong, rg. Lett.200, 2, ; (s) I. Takanori, M. Yusuke, H. Yukiko,. Takashi and M. Kazushi, J. rg. Chem. 2008, 73, ; (s2). Takashi, I. Takanori, M. Yusuke, Y. Asako and M. Kazushi, J. Am. Chem. Soc.2008, 30, ; (s3) X. Liu and W. Hu, J. Chem. Res. 2004, 8, ; (s4) B. Cherif, G. David and Y. Miguel, Synthesis. 2006, 39-34; (s5) E. H. White, M. Ribi, L.K. Cho, N. Egger, P. M. Dzadzic and, M. J. Todd, J. rg. Chem. 984, 49, ; (s6) A. Thierry, L. Aymeric, G. Yves, C. Herve, G. Laurent, T. Alphonse and B. Gerard, Angew. Chem. Int. Ed. 20, 50, ; (s7) M. Silja and P. Bernd, J. rg. Chem. 200, 75, ; (s8) S. Masumi and S. Takeshi, B. Chem. Soc. Jpn. 2004, 77, ; (s9) S. Huang, I. Hsei and C. Chen, Bioorg. Med. Chem. 2006, 4, ; (s20) B. Raymond and M. Gabriel, rg. Lett.2002, 4, ; (s2) Y. C. Chang, F. R. Chang and Y. C. Wu, J. Chin. Inst. Chem.. Soc.2000, 47, ; (s22) A. R. Katritzky, S. K. Singh, C. Cai and S. Bobrov, J. rg. Chem. 2006, 7, ; (s23) M. Toshikatsu, I. Kazuaki and Y. Hisashi, rg. Lett.2005, 7, ; (s24) D. Debapratim, R. Sangita and D. P. Kumar, rg. Lett.2004, 6, ; (s25) H. E. Bartrum, D. C. Blakemore, C. J. Moody and C. J. Hayes, Chem. Eur. J. 20, 7, ; (s26) C. T. Chen and Y. S. Munot, J. rg. Chem. 2005, 70, ; (s27) J. McNulty, J. J. Nair, S. Cheekoori, V. Larichev, A. Capretta and A. J. Robertson, Chem. Eur. J. 2006, 2, ; 2 / 67

22 S6. NMR spectra of all compounds Acetic acid 2 phenylethyl ester (4a) 22 / 67

23 Acetic acid 3 phenylpropyl ester (4b) 23 / 67

24 Acetic acid benzyl ester (4c) 24 / 67

25 Phenyl acetate (4d) 25 / 67

26 Benzhydryl acetate (4e) 26 / 67

27 cyclohexyl acetate (4f) 27 / 67

28 propane-,3-diyl diacetate (4g) 28 / 67

29 methyl cyclopentanecarboxylate (4i) 29 / 67

30 Methyl oleate (4j) 30 / 67

31 methyl benzoate (4k) 3 / 67

32 Br S methyl 5-bromotetrahydrothiophene-2-carboxylate (4l) 32 / 67

33 Butyl benzoate (4m) 33 / 67

34 Hexyl benzoate (4n) 34 / 67

35 n-heptyl benzoate (4o) 35 / 67

36 n-decyl benzoate (4p) 36 / 67

37 H n-decyl 4-hydroxybenzoate (4q) 37 / 67

38 Isobutyl benzoate (4r) 38 / 67

39 Prop-2-yn--yl benzoate (4t) 39 / 67

40 0 Undecenic acid 2 phenylethylester (4u) 40 / 67

41 Phenylethyl acrylate (4v) 4 / 67

42 Br Bromoacetic acid 2 phenylethyl ester (4w) 42 / 67

43 H 3 C(H 2 C) 7 (CH 2 ) 7 (CH 2 ) 5 CH 3 Cetyl oleate (4x) 43 / 67

44 Ethyl stearate (4y) 44 / 67

45 7 7 Ethyl oleate (4z) 45 / 67

46 H methyl 2-hydroxybenzoate (4a ) 46 / 67

47 H methyl 3-hydroxybenzoate (4b ) 47 / 67

48 H methyl 4-hydroxybenzoate (4c ) 48 / 67

49 Phenylethyl propionate (4d ) 49 / 67

50 Br Bromobutyricacid phenethyl ester (4e ) 50 / 67

51 Benzoic acid 2 phenylethyl ester (4f ) 5 / 67

52 H methyl 2-hydroxy-2-phenylacetate (6a) 52 / 67

53 H ethyl 2-hydroxy-2-phenylacetate (6b) 53 / 67

54 H propyl 2-hydroxy-2-phenylacetate (6c) 54 / 67

55 H butyl 2-hydroxy-2-phenylacetate (6d) 55 / 67

56 H hexyl 2-hydroxy-2-phenylacetate (6e) 56 / 67

57 H isopropyl 2-hydroxy-2-phenylacetate (6f) 57 / 67

58 H isobutyl 2-hydroxy-2-phenylacetate (6g) 58 / 67

59 H cyclohexyl 2-hydroxy-2-phenylacetate (6i) 59 / 67

60 H allyl 2-hydroxy-2-phenylacetate (6j) 60 / 67

61 H but-3-yn--yl 2-hydroxy-2-phenylacetate (6k) 6 / 67

62 H benzyl 2-hydroxy-2-phenylacetate (6m) 62 / 67

63 H phenethyl 2-hydroxy-2-phenylacetate (6n) 63 / 67

64 H 3-phenylpropyl 2-hydroxy-2-phenylacetate (6o) 64 / 67

65 H N 2 2-nitrobenzyl 2-hydroxy-2-phenylacetate (6p) 65 / 67

66 H Cyclandelate (6q) 66 / 67

67 Cyclandelate (R/S) which was purchased from Energy. 67 / 67