Highly Chemoselective Esterification Reactions and Boc/THP/TBDMS Discriminating Deprotections Under Samarium(III) Catalysis Table of Contents Pages

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1 Supporting information Highly Chemoselective Esterification Reactions and Boc/THP/TBDMS Discriminating Deprotections Under Samarium(III) Catalysis Pushparathinam Gopinath, Surapaneni Nilaya and Kannoth Manheri Muraleedharan * Department of Chemistry, Indian Institute of Technology Madras, Chennai, INDIA Table of Contents Pages 1. Experimental procedures, spectral- and analytical data H and 13 C NMR spectra of compound 1b H and 13 C NMR spectra of compound 2b H and 13 C NMR spectra of compound 3b H and 13 C NMR spectra of compound 4b H and 13 C NMR spectra of compound 5b H and 13 C NMR spectra of compound 6b H and 13 C NMR spectra of compound 7b H and 13 C NMR spectra of compound 8b H and 13 C NMR spectra of compound 9b H and 13 C NMR spectra of compound 10b H and 13 C NMR spectra of compound 11b H and 13 C NMR spectra of compound 12b H and 13 C NMR spectra of compound 13b H and 13 C NMR spectra of compound 15a H and 13 C NMR spectra of compound 15b H and 13 C NMR spectra of compound 15c H and 13 C NMR spectra of compound 15d H and 13 C NMR spectra of compound 15e H and 13 C NMR spectra of compound 15f H and 13 C NMR spectra of compound 15g H and 13 C NMR spectra of compound 15h H and 13 C NMR spectra of compound 16b H and 13 C NMR spectra of compound 18b H and 13 C NMR spectra of compound 19b H and 13 C NMR spectra of compound 20b 32 1

2 General experimental information: All reactions were carried out under nitrogen atmosphere and commercially available alcohols (methyl-, ethyl-,butyl-, isoamyl-, allyl-,benzyl-, isopropyl-,cyclohexyland tert-butyl alcohols) and SmCl 3 from Sigma Aldrich were used in esterification reactions. Thinlayer chromatography (TLC) was performed on 0.25 mm silica gel plates (60 F254 grade) from Merck, and were analyzed using either a 254 nm UV light or Ceric ammonium molybdate staining method. The chromatographic separation was carried out on mesh silica gel. Melting points were obtained on electro-thermal apparatus and are uncorrected. 1 H NMR and 13 C NMR spectra were recorded on Bruker Avance 400 MHz instrument, and the chemical shifts are reported in parts per million (ppm) relative to tetramethylsilane, with J values in Hertz. The splitting patterns in 1 H NMR spectra are reported as follows: s = singlet; d = doublet; t = triplet; q = quartet; dd = doublet of doublet; bs = broad singlet; quin = quintet; hept = heptet, dt = doublet of triplet; m = multiplet. 13 C NMR data are reported with the solvent peak (CDCl 3 = 77.0) as the internal standard. High-resolution mass spectra (HRMS) were recorded on a Waters Q-Tof micro TM spectrometer with lock spray source. Infrared spectra were recorded using a Nicolet 6700 FT-IR spectrophotometer. General procedure for esterification: A sealed reaction tube containing mixture of the carboxylic acid and SmCl 3 ( mol %) in appropriate alcohol (2 ml) was placed on a pre-heated oil bath (kept at o C). After ensuring completion of the reaction by TLC analysis, the excess alcohol was evaporated off and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to get the corresponding esters. 5-(3-Hydroxy-benzo[b]thiophen-2-yl)-3, 3-dimethyl-5-oxo-pentanoic acid ethyl ester (1b) 5-(3-hydroxybenzo[b]thiophen-2-yl)-3,3-dimethyl-5-oxopentanoic acid (150 mg, mmol) was esterified using SmCl 3 (3 mol%, 4 mg) in ethanol (2 ml) according to the general procedure discussed above at 80 o C for 72 h to get the ethyl ester 1b (154 mg, 94% yield). Analytical data for 1b: 1 H NMR (CDCl 3 ) δ 12.5 (bs, 1H), 7.98 (d, 1H, J = 8.0 Hz), 7.73 (d, 1H, J = 8.4 Hz), 7.53 (t, 1H, J = 7.6 Hz), 7.41 (t, 1H, J = 7.2 Hz), 4.13 (q, 2H, J = 7.2 Hz), 2.87 (s, 2H), 2.53 (s, 2H), 1.25 (t, 3H, J = 7.2 Hz), 1.21 (s, 6H); 13 C NMR (CDCl 3 ) δ 198.6, 171.9, 162.1, 139.0, 130.5, 129.8, 124.7, 123.8, 123.2, 112.5, 60.1, 50.4, 45.5, 33.8, 28.1(2C), 14.3; IR (neat) cm -1 : 2961, 2929, 1725, 1604, 1524, 1275, 1035, 766; HRMS (ESI) exact mass calcd. for C 17 H 21 4 S [M+H] , found [M+H] (3-Hydroxy-benzo[b]thiophen-2-yl)-5-oxo-3-phenyl-pentanoic acid ethyl ester (2b) 5-(3-Hydroxy-benzo[b]thiophen-2-yl)-5-oxo-3-phenyl-pentanoic acid (100 mg, mmol) was esterified using SmCl 3 (3 mol%, 2.3 mg) in ethanol (2 ml) according to the general procedure discussed above at 80 o C for 72 h to get desired ester 2b: (105 mg, 97% yield) as a pale yellow solid. Analytical data for 2b: mp C; 1 H NMR (CDCl 3 ) δ (bs, 1H), 7.95 (d, 1H, J = 8 Hz), 7.71 (d, 1H, J = 8 Hz), 7.52 (dd, 1H, J = 7.6, 8 Hz), 7.39 (dd, 1H, J = 7.2, 8 Hz), (m, 4H), (m, 1H), 4.04 (q, 2H, J = 7.2 Hz), 3.92 (qn, 1H, J = 7.4 Hz), 3.14 (m, 2H), (m. 1H), (m, 1H), 1.14 (t, 3H, J = 7.2 Hz); 13 C NMR (CDCl 3 ) δ 197.1, 171.5, 162.0, 142.7, 139.1, 130.4, 129.9, (2C), (2C), 127.0, 124.7, 123.8, 123.3, 111.4, 60.5, 46.8, 40.8, 37.8, 14.1; IR (neat) cm -1 : 2977, 1728, 1601, 1522, 1371, 1030, 732; HRMS (ESI) exact mass calcd. for C 21 H 21 4 S [M+H] , found [M+H] (2-ethoxy-2-oxoethyl)-5-nitrobenzoic acid (3b) A sealed reaction tube containing a mixture of Nitro homophthalic (250 mg, mmol) and SmCl 3 (1 mol%, 3 mg) in Ethyl alcohol (2 ml) was heated in an oil bath at 80 o C for 48 h. Ethanol was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the monoester 3b (260 mg, 93% yield) as a white crystalline solid. Analytical data for 3b: mp 110 C; 1 H NMR (CDCl 3 ) δ 8.97 (d, 1H, J = 2.4 Hz), 8.39 (dd, 1H, J = 8.4, 2.4 Hz), 7.51 (d, 1H, J = 8.4 Hz), (m, 4H), 1.28 (t, 3H, J = 7.2 Hz); 13 C NMR (CDCl 3 ) δ 170.2, , , 143.7, 133.7, , 127.4, 126.8, 61.4, 40.6, 14.1; IR (neat) cm -1 ; 3083, 2985, 1731, 1698, 1614, 1524, 1416; HRMS (ESI) exact mass calcd. for C 11 H 11 N 6 Na [M+Na] , found [M+ Na]

3 2-Methylene-succinic acid 4-ethyl ester (4b) and 2-methylene-succinic acid diethyl ester (4c) Itaconic acid (250 mg, mmol), was esterified using SmCl 3 (1 mol %, 5 mg) in ethanol (2 ml) according to the general procedure discussed above at 80 o C for 17 h to get 4b (288 mg, 96% yield) as a white crystalline solid along with its diester 4c (16 mg, 4% yield) as a gummy liquid. Analytical data for 4b: mp C; 1 H NMR (CDCl 3 ) δ 6.46 (s, 1H), 5.83 (s, 1H), 4.17 (q, 2H, J = 7.1 Hz), 3.34 (s, 2H), 1.26 (t, 3H, J = 7.1 Hz); 13 C NMR (CDCl 3 ) δ 171.3, 170.6, 133.3, 130.6, 61.0, 37.4, 14.1; IR (neat) cm -1 : 2987, 1730, 1725, 1636, 1433, 1269, 1197, 753; HRMS (ESI) exact mass calcd. for C 7 H 11 4 [M+H] , found [M+H] Analytical data for 5c: 1 H NMR (CDCl 3 ) δ 6.32 (s, 1H), 5.69 (s, 1H) 4.22 (q, 2H, J = 7.2 Hz), 4.14 (q, 2H, J = 7.2 Hz), 3.33 (s, 2H), 1.29 (t, 3H, J = 7.2 Hz), 1.26 (t, 3H, J = 7.2 Hz); 13 C NMR (CDCl 3 ) δ 170.7, 166.1, 134.1, 128.0, 60.9, 60.8, 37.7, 14.0 (2C); IR (neat) cm -1 : 2981, 1724, 1636, 1310, 1187, 1146, 1030; HRMS (ESI) exact mass calcd. for C 9 H 15 4 [M+H] +, found [M+H] Camphoric acid ethyl ester (5b) Camphoric acid (100 mg, 0.5 mmol), was esterified using SmCl 3 (5 mol%, 6.5 mg), in ethanol (2 ml) according to the general procedure discussed above at 80 o C for 96 h to get the mono ester 5b (95 mg, 83% yield), as a gummy oil. Analytical data for 5b: 1 H NMR (CDCl 3 ) δ (m, 2H), 2.73 (dd, 1H J = 9.2, 9.2 Hz), 2.46 (ddd, 1H, J = 12.4, 12.4, 7.6 Hz), (m, 1H), (m, 1H), 1.45 (ddd, 1H, J = 13.6, 9.6, 4.0 Hz), (m, 9H), 0.8 (s, 3H); 13 C NMR (CDCl 3 ) δ 182.3, 173.9, 60.3, 56.1, 52.7, 46.7, 32.2, 22.7, 22.4, 21.5, 21.2, 14.3; IR (neat) cm -1 : 2974, 1726, 1698, 1461, 1378, 1274, 1175, 752; HRMS (ESI) exact mass calcd. for C 12 H 21 4 [M+H] , found [M+H] Boc-AlaEt (6b) Boc- alanine (250 mg, 1.32 mmol) was esterified using SmCl 3 (10 mol%, 34 mg) in ethanol (2 ml), according to the general procedure discussed above for 144 h at 40 o C to get 6b (150 mg, 52% isolated yield) as a gummy liquid. After column chromatography, 60 mg of the starting Boc-Ala-H was also recovered. Analytical data for 6b: 1 H NMR (CDCl 3 ) δ 5.1(bs, 1H), 4.3 (bs, 1H), 4.2 (q, 2H, J = 7.12 Hz), 1.44 (s, 9H), 1.38 (d, 3H, J = 7.16 Hz), 1.26 (t, 3H, J = 7.12 Hz); 13 C NMR (CDCl 3 ) δ 173.4, 155.2, 79.8, 61.3, 49.3, 28.3 (3C), 18.7, 14.2,; IR (neat) cm -1 : 3365, 2985, 1706, 1514, 1448, 1360, 1264, 1162, 1059, 760; HRMS (ESI) exact mass calcd. for C 10 H 20 N 4 [M+H] , found [M+H] BocAlaAlaMe (7b) BocAlaAlaH (250 mg, 0.96 mmol) was esterified using SmCl 3 (10 mol%, 25 mg) in methanol (4 ml) according to the general procedure discussed above for 144 h at 50 o C to get 7b (142 mg, 54% isolated yield) as a white crystalline solid. After column chromatography, 50 mg of the starting material was also recovered. Analytical data for 7b: 1 H NMR (CDCl 3 ) δ 6.78 (brs, 1H), 5.15 (brd, 1H), (m, 1H), 4.2 (brs, 1H), 3.75 (s, 3H), 1.45 (s, 9H), 1.41 (d, 3H, J = 7.2 Hz), 1.36 (d, 3H, J = 7.2 Hz); 13 C NMR (CDCl 3 ) δ 173.2, 172.3, , 80.1, 52.4, 50.0, 48.0, 28.3(3C), 18.2 (2C); HRMS (ESI) exact mass calcd. for C 12 H 23 N 2 5, [M+H] found [M+H] Benzyloxycarbonylamino-pentanedioic acid diethyl ester (8b) N-Cbz protected glutamic acid (250 mg, 0.89 mmol) was esterified using SmCl 3 (1 mol%, 3 mg) in ethanol (3 ml) according to the general procedure discussed above at 80 o C for 48 h to get 8b (272 mg, 91% yield) as a gummy liquid; Analytical data for 8b: R f (25% EtAc /hexanes) 0.48; 1 H NMR (CDCl 3 ) δ (m, 5H), 5.43 (d, 1H, J = 7.2 Hz), 5.1 (s, 2H), 4.39 (m, 1H), 4.20 (q, 2H, J = 5.8 Hz), 4.12 (q, 2H, J = 7.2 Hz), (m, 2H), (m, 1H), (m, 1H), (m, 6H); 13 C NMR (CDCl 3 ) δ 172.7, 171.8, 155.9, 136.2, (2C), (2C), 128.1, 67.0, 61.6, 60.7, 53.4, 30.2, 27.7, 14.1 (2C); IR (neat) cm -1 : 3350, 3057, 2979, 1728, 1514, 1265, 1206, 1052, 746; ESI (m/z) 338 [M+H] +. Mandelic acid ethyl ester (9b) Mandelic acid (250 mg mmol) was esterified using SmCl 3 (1 mol %, 4.2 mg) in ethanol (2 ml) according to the general procedure discussed above at 80 o C for 16 h to get the desired ester 9b (283 mg, 96% yield) as colorless liquid. Analytical data for 9b: 1 H NMR (CDCl 3 ) δ (m, 5H), 5.15 (d, 1H, J = 5.2 Hz ), (m, 2H), 3.57 (d, 1H, J = 5.6 Hz), 1.22 (t, 3H, J = 7.2 Hz); 13 C NMR (CDCl 3 ) δ 173.6, 138.4, (2C), 128.4, (2C), 72.8, 62.2, 14.0; IR (neat) cm -1 : 3454, 2980, 3

4 2927, 1731, 1264, 1183, 1069, 738; HRMS (ESI) exact mass calcd. for C 10 H 12 3 Na [M+Na] , found [M+Na] Diethyl tartarate (10b) Tartaric acid (250 mg mmol) was esterified using SmCl 3 (0.1 mol%, 0.4 mg) in ethanol (2 ml) according to the general procedure discussed above at 80 o C for 46 h to get the desired diethyl ester 10b (329 mg, 96% yield) as colourless oil. Analytical data for 10b: 1 H NMR (CDCl 3 ) δ 4.55 (s, 2H), 4.33 (q, 4H, J = 7.16 Hz), (bs, 2H,), 1.33 (t, 6H, J = 7.16 Hz); 13 C NMR (CDCl 3 ) δ (2C), 72 (2C), 62.4 (2C), 14.1 (2C); IR (neat) cm -1 : 3476, 2981, 1735, 1298, 1234, 1085, 1017; HRMS (ESI) exact mass calcd. for C 8 H 15 6 (M+H) , found (M+H) Hydroxy-succinic acid diethyl ester (11b) Malic acid (140 mg, mmol), was esterified using SmCl 3 (0.5 mol%, 1.5 mg) in ethanol (2 ml) according to the general procedure discussed above at 80 o C for 48 h to get the desired diethyl ester 11b (186 mg, 94% yield). Analytical data for 11b: 1 H NMR (CDCl 3 ) δ 4.49 (dd, 1H, J = 5.2, 5.2 Hz), 4.27 (m, 2H), 4.18 (m, 2H), 3.3 (bs, 1H, H), (two dd merged, 2H), (two triplets merged, 6H); 13 C NMR (CDCl 3 ) δ 173.3, 170.5, 67.2, 61.9, 60.9, 38.7, 14.0 (2C); IR (neat) cm , 2984, 1729, 1376, 1169, 1101, 1024; HRMS (ESI) exact mass calcd. for C 8 H 14 5 Na [M+Na] , found [M+Na] Hydroxy-succinic acid 4-ethyl ester (11c) Malic acid (110 mg, 0.82 mmol), was esterified using SmCl 3 (1 mol%, 2 mg) in ethanol (2 ml) as discussed above and the reaction time was limited to 3 h to get the desired mono ester 11c (71 mg, 46% yield) along with diester 11b (40 mg, 30% yield) as colorless oils. Analytical data for 11c: 1 H NMR (CDCl 3 ) δ 6.37 (bs, 1H), 4.51 (dd, 1H, J = 4.4, 4.4 Hz), 4.27 (m, 2H), (two dd merged, 2H), 1.28 (t, 3H, J = 7.2 Hz); 13 C NMR (CDCl 3 ) δ , , 67.1, 62.2, 38.4, 14.1; IR (neat) cm -1 : 2923, 2856, 1726, 1268, , 4, 5-Trihydroxy-benzoic acid methyl ester (12b) 3, 4, 5-Trihydroxy-benzoic acid (300 mg, mmol), was esterified using SmCl 3 (10 mol%, 45 mg) in methanol (4 ml) according to the general procedure discussed above at 80 o C for 130 h to get the desired ester 12b (260 mg, 74% yield), as yellow solid; Analytical data for 12b: 1 H NMR (CDCl 3 +CD 3 D) δ 7.11 (s, 2H), 4.1 (bs, 3H), 3.8 (s, 3H); 13 C NMR (CDCl 3 +CD 3 D) δ 167.8, (2C), 137.7, 120.3, (2C), HRMS (ESI) exact mass calcd. for C 8 H 9 5 [M+H] , found [M+H] Cinnamic acid ethyl ester (13b) Cinnamic acid (100 mg, mmol), was esterified using SmCl 3 (10 mol%, 17 mg) in ethanol (2 ml) according to the general procedure discussed above at 80 o C for 96 h to get 13b (113 mg, 96% yield), Analytical data for 13b: 1 H NMR (CDCl 3 ) δ 7.69 (d, 1H, J = 16 Hz), (m, 2H), (m, 3H), 6.44 (d, 1H, J = 16.4 Hz), 4.27 (q, 2H, J = 7.2 Hz), 1.34 (t, 3H, J = 7.2 Hz); 13 C NMR (CDCl 3 ) δ 167, 144.6, 134.6, 130.2, (2C), (2C), 118.3, 60.5, 14.3; IR (neat) cm -1 : 2989, 1708, 1636, 1451, 1312, 1266, 1034, 981; HRMS (ESI) exact mass calcd. for C 11 H 13 2 (M+H) , found (M+H) (2-methoxy-2-oxoethyl)benzoic acid (15a) A sealed reaction tube containing a mixture of homophthalic acid (250 mg, mmol) and SmCl 3 (1 mol%, 4 mg) in methanol (3 ml) was heated in an oil bath at 80 o C for 8 h. Methanol was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the monoester 15a (260 mg, 97% yield) as a white crystalline solid. Analytical data for 15a: mp C; 1 H NMR (CDCl 3 ) δ 8.15 (d, 1H, J = 7.6 Hz), 7.54 (t, 1H, J = 7.2 Hz), 7.41 (t, 1H, J = 7.6 Hz), 7.29 (d, 1H, J = 7.6 Hz), 4.07 (s, 2H), 3.71 (s, 3H); 13 C NMR (CDCl 3 ) δ 172.5, 172, 136.8, 133.3, 132.4, 131.9, 128.5, 127.6, 52.0, 40.6; IR (neat) cm -1 ; 2951, 2510, 1702, 1578, 1403, 1272, 1005; HRMS (ESI) exact mass calcd. for C 10 H 11 4 [M+H] , found [M+H] Ethoxycarbonylmethyl-benzoic acid (15b) 4

5 A sealed reaction tube containing a mixture of homophthalic acid (250 mg mmol) and SmCl 3 (1 mol%, 4 mg) in ethanol (2 ml) was heated in an oil bath at 80 o C for 10 h. Ethanol was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the monoester 15b (286 mg, 99% yield) as a white crystalline solid. Analytical data for 15b: mp 106 C; 1 H NMR (CDCl 3 ) δ 8.13 (d, 1H, J = 7.6 Hz), 7.53 (dt, 1H, J = 7.2, 1.2 Hz), 7.39 (dt, 1H, J = 7.6, 0.8 Hz), 7.28 (d, 1H, J = 7.6 Hz), 4.17 (q, 2H, J = 7.2 Hz), 4.05 (s, 2H), 1.26 (t, 3H, J = 7.2 Hz); 13 C NMR (CDCl 3 ) δ 172.5, 171.5, 136.9, 133.2, 132.4, 131.9, 128.7, 127.5, 60.8, 40.8, 14.1; IR (neat) cm -1 ; 2979, 2648, 2522, 1728, 1674, 1406, 1274, 1172, 925; HRMS (ESI) exact mass calcd. for C 11 H 13 4 [M+H] , found [M+H] (2-butoxy-2-oxoethyl)benzoic acid (15c) A sealed reaction tube containing a mixture of homophthalic acid (250 mg mmol) and SmCl 3 (5 mol%, 18 mg) in isobutanol (3 ml) was heated in an oil bath at 90 o C for 40 h. Isobutanol was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the monoester 15c (295 mg, 90% yield) as a white crystalline solid. Analytical data for 15c: mp C; 1 H NMR (CDCl 3 ) δ 8.27 (d, 1H, J = 7.2 Hz), 7.53 (dt, 1H, J = 7.8, 1.2 Hz), 7.4 (dt, 1H, J = 7.6, 0.8 Hz), 7.29 (d, 1H, J = 7.6 Hz), 4.11 (t, 2H, J = 6.8 Hz), 4.06 (s, 2H), 1.6 (qt, 2H, J = 7.6 Hz),1.36 (sextet, 2H, J = 7.2 Hz), 0.91 (t, 3H, J = 7.6 Hz); 13 C NMR (CDCl 3 ) δ 172.5, 171.6, 137.0, 133.2, 132.4, 131.9, 128.6, 127.5, 64.5, 40.8, 30.6, 19.1, 13.6; IR (neat) cm -1 ; 3073, 2969, 2933, 2874, 1728, 1686, 1576, 1407, 1302; HRMS (ESI) exact mass calcd. for C 13 H 17 4 [M+H] , found [M+H] (2-(isopentyloxy)-2-oxoethyl)benzoic acid (15d) A sealed reaction tube containing a mixture of homophthalic acid (250 mg, mmol) and SmCl 3 (5 mol%, 18 mg) in isoamyl alcohol (3 ml) was heated in an oil bath at 90 o C for 48 h. Isoamyl alcohol was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the monoester 15d (311 mg, 90% yield) as a white crystalline solid. Analytical data for 15d: mp C; 1 H NMR (CDCl 3 ) δ 8.14 (d, 1H, J = 7.6 Hz), 7.54 (t, 1H, J = 7.2, Hz), 7.40 (t, 1H, J = 7.6, Hz), 7.28 (d, 1H, J = 7.6 Hz), 4.14 (t, 2H, J = 7 Hz), 4.06 (s, 2H), 1.66 (hept, 1H, J = 6.4 Hz), 1.52 (q, 2H, J = 6.6 Hz), 0.89 (d, 6H, J = 6.4 Hz); 13 C NMR (CDCl 3 ) δ , 171.6, 137.0, 133.2, 132.4, 131.9, 128.6, 127.5, 63.5, 40.8, 37.2, 25.0, 22.4(2C); IR (neat) cm -1 ; 3074,2960, 2870, 2654, 1734, 1687, 1410, 1349, 1300; HRMS (ESI) exact mass calcd. for C 14 H 19 4 [M+H] , found [M+H] (2-(allyloxy)-2-oxoethyl)benzoic acid (15e) A sealed reaction tube containing a mixture of homophthalic acid (250 mg, mmol) and SmCl 3 (5 mol%, 18 mg) in allyl alcohol (3 ml) was heated in an oil bath at 90 o C for 48 h. Allyl alcohol was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the monoester 15e (250 mg, 82% yield) as a white crystalline solid. Analytical data for 15e: mp C; 1 H NMR (CDCl 3 ) δ 8.15 (d, 1H, J = 7.6 Hz), 7.54 (t, 1H, J = 7.6 Hz), 7.41 (t, 1H, J = 7.6 Hz), 7.29 (d, 1H, J = 7.6 Hz), (m, 1H), 5.29 (bdt, 1H), 5.21 (bd, 1H), (m, 2H), 4.62 (b dd), 4.09 (s, 2H) ; 13 C NMR (CDCl 3 ) δ 172.5, 171.1, 136.7, 133.3, 132.4, 132.1, 131.9, 128.6, 127.6, 118.3, 65.5, 40.7; IR (neat) cm -1 ; 3433, 2934, 1727, 1686, 1577, 1417, 1263; HRMS (ESI) exact mass calcd. for C 12 H 12 4 Na [M+Na] , found [M+Na] (2-(benzyloxy)-2-oxoethyl)benzoic acid (15f) A sealed reaction tube containing a mixture of homophthalic (250 mg, mmol) and SmCl 3 (5 mol%, 18 mg) in benzyl alcohol (2 ml) was heated in an oil bath at 110 o C for 48 h. Added 4 ml of Sat. NaHC 3 in to the reaction mixture. Extracted with ethyl acetate. Solvent was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the monoester 15f (250 mg, 67% yield) as a white crystalline solid. Analytical data for 15f: mp C; 1 H NMR (CDCl 3 ) δ 8.15 (d, 1H, J = 7.6 Hz), 7.55 (t, 1H, J = 7.2 Hz), 7.41 (t, 1H, J = 7.6 Hz), 7.33 (d, 4H, J = 3.6 Hz), 7.29 (d, 2H, J = 7.6 Hz), 5.15 (s, 2H), 4.11 (s, 2H); 13 C NMR (CDCl 3 ) δ , , , , , , , (2C), (2C), 5

6 128.11(2C), , 66.58, 40.77; IR (neat) cm -1 ; 2946, 1737, 1680, 1574, 1456, 1410; HRMS (ESI) exact mass calcd. for C 16 H 15 4 [M+H] , found [M+H] (2-(cyclohexyloxy)-2-oxoethyl)benzoic acid (15g) A sealed reaction tube containing a mixture of homophthalic (100 mg, 0.56 mmol) and SmCl 3 (5 mol%, 7.1 mg) in cyclohexanol (0.3 ml) and toulene 3ml was heated in an oil bath at 110 o C for 48 h. Then the residue was chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the monoester 15g (120 mg, 83% yield) as a white crystalline solid. Analytical data for 15g: mp C; 1 H NMR (CDCl 3 ) δ 8.13 (d, 1H, J = 7.2 Hz), 7.53 (dt, 1H, J = 7.2, 0.8 Hz), 7.39 (dt, 1H, J = 7.6, 1.2 Hz), 7.28 (d, 1H, J = 6.4 Hz), 4.81 (d, 1H, J = 8.6 Hz), 4.03 (s, 2H), (m, 2H), (m, 2H), (m, 3H), (m, 3H); 13 C NMR (CDCl 3 ) δ 172.6, 170.9, 137.1, 133.2, , 131.8, , 127.4, 73.01, 41.15, (2C), 25.35, (2C); IR (neat) cm -1 ; 2935, 1730, 1687, 1576, 1415, 1299; HRMS (ESI) exact mass calcd. for C 15 H 19 4 [M+H] , found [M+H] (2-isopropoxy-2-oxoethyl)benzoic acid (15h) A sealed reaction tube containing a mixture of homophthalic acid (100 mg, 0.55 mmol) and SmCl 3 (5 mol%, 7.1 mg) in IPA (3 ml) was heated in an oil bath at 90 o C for 32 h. IPA was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the monoester 15h (123 mg, 99% yield) as a white crystalline solid. Analytical data for 15h: mp C; 1 H NMR (CDCl 3 ) δ 8.13 (d, 1H, J = 7.6 Hz), 7.54 (t, 1H, J = 8 Hz), 7.4 (t, 1H, J = 7.6 Hz), 7.28 (d, 1H, J = 7.6 Hz), 5.04 (heptet, 1H, J = 4.8 Hz), 4.01 (s, 2H), 1.2 (dd, 6H, J = 6.4, 1.9 Hz); 13 C NMR (CDCl 3 ) δ 172.5, , 137.1, 133.2, 132.4, 131.9, 128.7, 127.5, 68.2, 41.1, 21.7 (2C); IR (neat) cm -1 ; 3068, 2986, 1731, 1680, 1581, 1417, 1308; HRMS (ESI) exact mass calcd. for C 12 H 15 4 [M+H] , found [M+H] N-Boc-ethanolamine (16b) A sealed reaction tube containing a mixture of tert-butyl 2-(tert-butyldimethylsilyloxy)ethylcarbamate (100 mg, mmol) and SmCl 3 (1 mol%, 1 mg) in ethyl alcohol (2 ml) was heated in an oil bath at 80 o C for 16 h. Ethanol was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford Boc-ethanolamine 16b (58 mg, 99% yield) as a liquid. Analytical data for 16b: 1 H NMR (CDCl 3 ) δ 5.13 (bs, 1H) 3.65 (t, 2H, J = 5.04 Hz), 3.25 (bd, 2H), (bs, 1H), 1.42 (s, 9H); 13 C NMR (CDCl 3 ) δ 156.8, 79.61, 62.3, 43.0, (3C); HRMS (ESI) exact mass calcd. for C 17 H 16 N 3 (M+H) , found (M+H) (tetrahydro-2H-pyran-2-yloxy)ethanol (18b) A sealed reaction tube containing a mixture of tert-butyl 2-(tetrahydro-2H-pyran-2- yloxy)ethylcarbamate (100 mg, 0.38 mmol) and SmCl 3 (1 mol%, 1 mg) in ethyl alcohol (2 ml) was heated in an oil bath at 40 o C for 40 h. Ethanol was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the 18b (52 mg, 85% yield) as a liquid. Analytical data for 18b: 1 H NMR (CDCl 3 ) δ 4.57 (dd, 1H, J = 2.8, 5.2 Hz), (m, 1H), (m, 4H), (m, 1H), 2.85 (t, 1H, J = 6.8 Hz), (m, 2H), (m, 4H); 13 C NMR (CDCl 3 ) δ 100.3, 70.9, 63.4, 62.3, 30.9, 25.3, 20.1; HRMS (ESI) exact mass calcd. for C 7 H 15 3 (M+H) found (M+H) ,3-dihydroxypropyl acetate (19b ) A sealed reaction tube containing a mixture of (2,2-dimethyl-1,3-dioxolan-4-yl)methyl acetate (100 mg, mmol) and SmCl 3 (1 mol%, 1.5 mg) in Ethyl alcohol (2 ml) was heated in an oil bath at 80 o C for 7 h. Ethanol was then evaporated and the residue chromatographed on silica gel using ethyl acetatehexane solvent system in a gradient mode to afford the mono acetate 19b (68 mg, 88% yield) as a gummy liquid. Analytical data for 19b : 1 H NMR (CDCl 3 ) δ (m, 2H ),3.93 (pentet, 1H, J = 4.8 Hz), 3.69 (dd, 1H, J = 3.6, 11.6 Hz), 3.59 (dd, 1H, J = 6, 11.6 Hz) (bs, 1H), (bs, 1H); 13 C NMR (CDCl 3 ) δ , 70.12, 65.29, 63.3, 20.83; HRMS (ESI) exact mass calcd. for C 5 H 11 4 [M+H] , found [M+ H] (3-hydroxyphenyl)ethyl acetate (20b ) 6

7 A sealed reaction tube containing a mixture of 3-(1-acetoxyethyl)phenyl acetate (150 mg, 0.67 mmol) and SmCl 3 (1 mol%, 2 mg) in Ethyl alcohol (2 ml) was heated in an oil bath at 80 o C for 24 h. Ethanol was then evaporated and the residue chromatographed on silica gel using ethyl acetate-hexane solvent system in a gradient mode to afford the monoacetate 20b (91 mg, 76% yield) as a liquid. Analytical data for 20b: 1 H NMR (CDCl 3 ) δ 7.19 (t, 1H, J = 8 Hz), 6.89 (d, 1H, J = 7.6 Hz), 6.82 (s, 1H), 6.75 (dd, 1H, J = 8.4, 2.4 Hz), (bs, 1H), 5.81 (q, 1H, J = 6.4 Hz), (s, 3H), 1.51(d, 3H, J = 6.4 Hz); 13 C NMR (CDCl 3 ) δ , , , , , , , 72.51, 22.07, 21.35; HRMS (ESI) exact mass calcd. for C 10 H 12 3 Na [M+Na] , found [M+ Na] Solvent screening for effective deprotection SmCl 3 H H 80 o C I H II H a after 44 h; b after 3 h To a solution of glycerol acetonide (I) in 2 ml of appropriate solvent, Solvent Toluene DMF DCE ACN % Yield NR NR NR 25 a was added SmCl 3 (10 mol%), and the mixture was heated in a sealed tube for 2 d. The solvent was removed under reduced pressure and the residue chromatographed on silica gel using ethyl acetate hexane THF <10% EtH Quantitative b a after 44 h; b after 3 h mixture as the solvent system to get glycerol (II). Results from experiments using ethanol, toluene, DMF, DCE, CH 3 CN and THF are presented in the table attached. ur literature search revealed that SmCl 3 in combination with acetyl chloride/tmscl can deprotect acetal and ketal functionalities. 1,2 To the best of our knowledge, the ability of SmCl 3 to selectively deprotect one acid labile protecting group in presence of another is not yet explored. 1. Wu, S.-H.; Ding, Z.-B. Synth. Commun. 1994, 24, Ukaji, Y.; Koumoto, N.; Fujisawa, T. Chem. Lett. 1989,

8 1 H and 13 C NMR Spectra of some of the selected esters H S 1b 13 C NMR, 100 MHz, CDCl 3 8

9 H S 2b 1 H NMR, 400 MHz, CDCl 3 H S 2b 13 C NMR, 100 MHz, CDCl 3 9

10 C 2 H 2 N 3b 1 H NMR, 400 MHz, CDCl 3 C 2 H 2 N 3b 13 C NMR, 100 MHz, CDCl 3 10

11 H 2 C 4b 1 H NMR, 400 MHz, CDCl 3 H 2 C 4b 13 C NMR, 100 MHz, CDCl 3 11

12 H 2 C H 5b 1 H NMR, 400 MHz, CDCl 3 H 2 C H 5b 13 C NMR, 100 MHz, CDCl 3 12

13 H BCHN 6b 1 H NMR, 400 MHz, CDCl 3 H BCHN 6b 13 C NMR, 100 MHz, CDCl 3 13

14 14

15 Et 2 C H CbzHN ( ) 2 8b 1 H NMR, 400 MHz, CDCl 3 Et 2 C CbzHN H ( ) 2 8b 13 C NMR, 100 MHz, CDCl 3 15

16 H 9b 1 H NMR, 400 MHz, CDCl 3 H 9b 13 C NMR, 100 MHz, CDCl 3 16

17 17

18 Et 2 C H 11b 1 H NMR, 400 MHz, CDCl 3 Et 2 C H 11b 13 C NMR, 100 MHz, CDCl 3 18

19 H C 2 Me H H 12b 1 H NMR, 400 MHz, CDCl 3 H C 2 Me H H 12b 13 C NMR, 100 MHz, CDCl 3 19

20 20

21 CH CH 3 15a 1 H NMR, 400 MHz, CDCl 3 CH CH 3 15a 13 C NMR, 100 MHz, CDCl 3 21

22 CH Et 15b 13 C NMR, 100 MHz, CDCl 3 22

23 CH 15c 1 H NMR, 400 MHz, CDCl 3 CH 15c 13 C NMR, 100 MHz, CDCl 3 23

24 CH 15d 1 H NMR, 400 MHz, CDCl 3 CH 15d 13 C NMR, 100 MHz, CDCl 3 24

25 CH 15e 1 H NMR, 400 MHz, CDCl 3 CH 15e 13 C NMR, 100 MHz, CDCl 3 25

26 CH Bn 15f 1 H NMR, 400 MHz, CDCl 3 CH Bn 15f 13 C NMR, 100 MHz, CDCl 3 26

27 CH 15g 1 H NMR, 400 MHz, CDCl 3 CH 15g 13 C NMR, 100 MHz, CDCl 3 27

28 CH 15h 1 H NMR, 400 MHz, CDCl 3 CH 15h 13 C NMR, 100 MHz, CDCl 3 28

29 BocHN H 16b 1 H NMR, 400 MHz, CDCl 3 BocHN H 16b 13 C NMR, 100 MHz, CDCl 3 29

30 H THP 18b 1 H NMR, 400 MHz, CDCl 3 H THP 18b 13 C NMR, 100 MHz, CDCl 3 30

31 H H Ac 19b 1 H NMR, 400 MHz, CDCl 3 H H Ac 19b 13 C NMR, 100 MHz, CDCl 3 31

32 Ac H 20b 1 H NMR, 400 MHz, CDCl 3 Ac H 20b 13 C NMR, 100 MHz, CDCl 3 32