Phosphine oxide-catalyzed dichlorination reactions of. epoxides

Phosphine oxide-catalyzed dichlorination reactions of epoxides Ross M. Denton*, Xiaoping Tang and Adam Przeslak School of Chemistry, The University of Nottingham, University Park, Nottingham, NG 2RD, United Kingdom E-mail: ross.denton@nottingham.ac.uk Table of Contents General remarks General procedures Characterization of dichloride products Characterization of esters and chlorohydrins NMR spectra NMR spectra of esters and chlorohydrins S2 S3 S4 S11 S15 S28 S1

General remarks Glassware was dried in an oven overnight before use. Thin layer chromatography was carried out on Polgram SIL G/UV254 silica-aluminium plates and plates were visualised using ultra-violet light (254 nm) and KMnO 4 solution. For flash column chromatography Fluorochem silica gel 60, 35-0 µ was used. NMR data was collected at either 20, or 400 MHz. Data was manipulated directly from the spectrometer or via a networked PC with appropriate software. All samples were analysed in CD 3 unless otherwise stated. Multiplicities for coupled signals designated using the following abbreviations: s=singlet, d=doublet, t=triplet, q=quartet, quin=quintet, sex=sextet, br=broad signal, ap=apparent and are given in Hz. 13 C multiplicities were assigned using a DEPT sequence. Where appropriate, COSY, HMQC and HMBC experiments were performed to aid assignment. High-resolution mass spectrometric data are quoted to four decimal places (0.1 mda) with error limits for acceptance of +/-5.0 ppm (defined as calcd./found mass 10-6). Mass spectra were acquired on a VG micromass 0E, VG autospec or micromass LCTOF. Infrared spectra were recorded on a Pelkin-Elmer 1600 FTIR instrument as dilute chloroform solutions or via analysis of neat samples using an ATR accessory. All solvents and reagents were used as supplied. Known compounds were characterized by comparison with reported literature data. S2

General Procedure A Triphenylphosphine oxide (42 mg, 0.15 mmol, 15 mol%) was dissolved in chloroform (1.0 ml), oxalyl chloride (12 µl, 0.14 mmol, 14 mol%) was then added, elution of gas was observed. After stirring at room temperature for 2 minutes, 0.8 ml solution of epoxide (1.0 mmol) and 2,6-di-tertbutyl pyridine (0.33 ml, 1.5 mmol) in chloroform and 0.8 ml solution of oxalyl chloride (98 µl, 1.2 mmol) in chloroform were added by syringe pump over 6 hours. The yield was then determined via internal standard (see below) or the reaction mixture was then concentrated in vacuo and the product isolated by flash column chromatography (silica, Et 2 O/Petrolumn ether: 5/95). General Procedure B Triphenylphosphine oxide (42 mg, 0.15 mmol, 15 mol%) was dissolved in benzene (1.0 ml), oxalyl chloride (12 µl, 0.14 mmol, 14 mol%) was then added, elution of gas was observed. After stirring at room temperature for 2 minutes, 0.8 ml solution of epoxide (1.0 mmol) and 2,6-di-tertbutyl pyridine (0.33 ml, 1.5 mmol) in benzene and 0.8 ml solution of oxalyl chloride (98 µl, 1.2 mmol) in benzene were added by syringe pump over 6 hours at 80 o C. The yield was then determined via internal standard (see below) or the reaction mixture was then concentrated in vacuo and the product isolated by flash column chromatography (silica, Et 2 O/Petrolumn ether: 5/95). Calculation of yield using tetrachloroethane as an internal standard When the reaction was completed, tetrachloroethane (50 µl, 0.4 mmol) was added as internal standard. The 1 H NMR spectrum was then recorded and the mass of the product calculated according to the equation below: mass Product = (area Product /area standard ) (MW Product /MW standard ) mass standard n m Where n corrects for the amount of the crude reaction mixture used and m corrects for S3

the number of protons associated with the resonance used. The integral of the proton(s) adjacent to was used in all cases otherwise indicated. Characterization of dichloride products 1,2-Dichlorododecane 4a 1,2-Epoxydodecane (0.22 ml, 1.0 mmol) was treated according to the general procedure A. The product (193 mg, 81% yield) was obtained as a colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm 4.10-4.03 (m, 1H, CH), 3.9 (dd, J = 11.3 and 5.2 Hz, 1H, CH 2 ), 3.68 (dd, J = 11.3 and.4 Hz, 1H, CH 2 ), 2.06-1.9 (m, 1H, CH 2 CH), 1.9-1.0 (m, 1H, CH 2 CH), 1.64-1.53 (m, 1H, CH 2 CH 2 CH), 1.50-1.39 (m, 1H, CH 2 CH 2 CH), 1.38-1.22 (br m, 14H), 0.92 (t, J = 6.9 Hz, 3H, CH 3 CH 2 ). 13 C NMR (100 MHz, CD 3 ) δ ppm 61.2 (CH), 48.2 (CH 2 ), 35.0 (CH 2 ), 31.9 (CH 2 ), 29.5 (CH 2 ), 29.5 (CH 2 ), 29.4 (CH 2 ), 29.3 (CH 2 ), 29.0 (CH 2 ), 25.8 (CH 2 ), 22. (CH 2 ), 14.1 (CH 3 ). HRMS: [M-C 6 H 13 ] - C 6 H 11 2, found 153.0232, theoretical mass 153.0232. IR ν max (CH 3 solution): 2928, 2855, 1601, 1466. Elemental Analysis: C 12 H 24 2 (238.125): calcd. C 60.25, H 10.11; found C 60.46, H 10.18.,8-dichlorooct-1-ene 4b 1,2-Epoxy--octene (0.15 ml, 1.0 mmol) was treated according to the general procedure A. The product (140 mg, 8% yield) was obtained as a colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm 5.89-5.9 (m, 1H, CH=CH 2 ), 5.05 (ddd, J = 1.1, 3.4 and 1.4 Hz, 1H, CH 2 =CH), 5.00 (tdd, J = 10.2, 2.1 and 1.4 Hz, 1H, CH 2 =CH), 4.10-4.03 (m, 1H, CH), 3.80 (dd, J = 11.3 and 5.1 Hz, 1H, CH 2 ), 3.68 (dd, J = 11.3 and.5 Hz, 1H, CH 2 ), 2.14-2.08 (m, 2H), 2.08-2.00 (m, 1H), 1.80-1.1 (m, S4

1H), 1.65-1.56 (m, 1H), 1.52-1.42 (m, 3H). 13 C NMR (100 MHz, CD 3 ) δ ppm 138.4 (CH), 114. (CH 2 ), 61.1 (CH), 48.2 (CH 2 ), 34.9 (CH 2 ), 33.4 (CH 2 ), 28.2 (CH 2 ), 25.2 (CH 2 ). IR ν max (CH 3 solution): 309, 3011, 299, 293, 2861, 1640, 1462, 995, 916. Elemental Analysis: C 8 H 14 2 (180.04): calcd. C 53.06, H.9; found C 53.33, H.82. (1,2-dichloroethyl)benzene 1 4c Styrene oxide (0.11 ml, 1.0 mmol) was treated according to the general procedure A. The product (99 mg, 5% yield) was obtained as a colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm.45-.38 (m, 5H, H Ar ), 5.03 (dd, J =.9 and 6.6 Hz, 1H, CH), 4.03 (dd, J = 11.3 and 6.6 Hz, 1H, CH 2 ), 3.96 (dd, J = 11.3 and.9 Hz, 1H, CH 2 ). 13 C NMR (100 MHz, CD 3 ) δ ppm 138.0 (Cq), 129.1 (CH), 128.8 (2 CH), 12.4 (2 CH), 61. (CH), 48.3 (CH 2 ). HRMS: [M] - C 8 H 8 2, found 13.999, theoretical mass 13.9998. IR ν max (CH 3 solution): 3068, 3011, 2954, 292, 2855, 1602, 1493, 1455. Elemental Analysis: C 8 H 8 2 (13.999): calcd. C 54.89, H 4.61; found C 54.54, H 4.4. tbu Ph Si Ph O tert-butyl(3,4-dichlorobutoxy)diphenylsilane 4e tert-butyl(2-(oxiran-2-yl)ethoxy)diphenylsilane (326 mg, 1.00 mmol) was treated according to the general procedure A. The product (236 mg, 62% yield) was obtained as a colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm.84-.80 (m, 4H, H Ar ), 1 W. Adam, C. Mock-Knoblauch, C. R. Saha-Moller and M. Herderich, J. Am. Chem. Soc., 2000, 9685-9691. S5

.5-.48 (m, 6H, H Ar ), 4.56-4.50 (m, 1H, CH), 4.05-3.99 (m, 1H, CH 2 OTBDPS), 3.98-3.89 (m, 2H, CH 2 OTBDPS + CH 2 ), 3.84 (dd, J = 11.4 and 6.9 Hz, 1H, CH 2 ), 2.44-2.35 (m, 1H), 2.00-1.92 (m, 1H), 1.21 (s, 9H, tbu). 13 C NMR (100 MHz, CD 3 ) δ ppm 135. (d, J = 3.2 Hz, 2 CH), 133.5 (d, J = 9.8 Hz, Cq), 129.8 (CH), 12.8 (2 CH), 60.1 (CH 2 ), 58.1 (CH), 48.8 (CH 2 ), 38.0 (CH 2 ), 26.9 (3 CH 3 ), 19.3 (Cq). HRMS: [M + Na + ] C 20 H 26 2 NaOSi, found 403.1023, theoretical mass 403.1022. IR ν max (CH 3 solution): 301, 3008, 2960, 2932, 2885, 2859, 142, 1428, 1112. Elemental Analysis: C 20 H 26 2 OSi (380.113): calcd. C 62.98, H 6.8; found C 62.92, H 6.69. (2,3-Dichloropropyl)benzene 4d 2-Benzyloxirane (134 mg, 1.00 mmol) was treated according to the general procedure A. The product (124 mg, 66% yield) was obtained as a colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm.39-.35 (m, 2H, ortho-h Ar ),.33-.28 (m, 3H, meta-h Ar and para-h Ar ), 4.32-4.26 (m, 1H, CH), 3.6 (dd, J = 11.4 and 4.8 Hz, 1H, CH 2 ), 3.69 (dd, J = 11.4 and 6.9 Hz, 1H, CH 2 ), 3.34 (dd, J = 14.2 and 5. Hz, 1H, CH 2 Ph), 3.10 (dd, J = 14.2 and.3 Hz, 1H, CH 2 Ph). 13 C NMR (100 MHz, CD 3 ) δ ppm 136.3 (Cq), 129.5 (2 CH), 128.5 (2 CH), 12.2 (CH), 60.9 (CH), 4.4 (CH 2 ), 41.0 (CH 2 ). HRMS: [M] - C 9 H 10 2, found 188.014, theoretical mass 188.0154. IR ν max (CH 3 solution): 3010, 292, 1603, 149, 1454. Elemental Analysis: C 9 H 10 2 (188.016): calcd. C 5.1, H 5.33; found C 5.1, H 5.35. S6

tbu Ph Si Ph O (+)-tert-butyl(-2,3-dichlorohexyloxy)diphenylsilane 2 4g tert-butyldiphenyl((3-propyloxiran-2-yl)methoxy)silane (354 mg, 1.00 mmol) was treated according to the general procedure B. The product (188 mg, 46% yield) was obtained as a colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm.6-.3 (m, 4H, H Ar ),.52-.43 (m, 6H, H Ar ), 4.43-4.38 (m, 1H, CH), 4.15-4.11 (m, 2H, CH 2 OTBDPS), 3.96 (m, 1H, CH), 2.03-1.95 (m, 1H), 1.8-1.8 (m, 1H), 1.5-1.66 (m, 1H), 1.5-1.45 (m, 1H), 1.13 (s, 9H, tbu), 1.01 (t, J =.4 Hz, 3H). 13 C NMR (100 MHz, CD 3 ) δ ppm 135.6 (d, J = 3. Hz, 2 CH), 132.9 (d, J = 2.9 Hz, Cq), 129.9 (CH), 12.8 (2 CH), 65.2 (CH 2 ), 65.1 (CH), 61. (CH), 35.9 (CH 2 ), 26. (3 CH 3 ), 19.3 (Cq), 19.2 (CH 2 ), 13.4 (CH 3 ). HRMS: [M + Na + ] C 22 H 30 2 NaOSi, found 431.1340, theoretical mass 431.135. tbu Ph Si Ph O (+)-tert-butyl(-2,3-dichlorohexyloxy)diphenylsilane 2 4f tert-butyldiphenyl((3-propyloxiran-2-yl)methoxy)silane (354 mg, 1.00 mmol) was treated according to the general procedure B. The product (19 mg, 44% yield) was obtained as a colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm.2-.6 (m, 4H, H Ar ),.50-.40 (m, 6H, H Ar ), 4.52-4.48 (m, 1H, CH), 4.11-4.0 (m, 1H), 4.03-3.98 (m, 1H), 3.86 (dd, J = 10.2 and 5.5 Hz, 1H), 2.00-1.91 (m, 1H), 1.88-1.9 (m, 1H), 1.65-1.58 (m, 1H), 1.54-1.46 (m, 1H), 1.10 (s, 9H, tbu), 1.00 (t, J =.4 Hz, 3H). 13 C 2 T. Yoshimitsu, N. Fukumoto and T. Tanaka, J. Org. Chem., 2009, 4, 696-02. S

NMR (100 MHz, CD 3 ) δ ppm 135.6 (d, J = 9.6 Hz, 2 CH), 132.8 (Cq), 129.9 (CH), 12.8 (2 CH), 64.9 (CH 2 ), 63. (CH), 61.2 (CH), 3.6 (CH 2 ), 26. (3 CH 3 ), 19.8 (CH 2 ), 19.2 (Cq), 13.4 (CH 3 ). HRMS: [M C 4 H 10 ] - C 18 H 20 OSi, found 315.090, theoretical mass 315.0966. (+)-2,3-Dichlorooctane 3 4h 2,3-Epoxy-octane (128 mg, 1.00 mmol) was treated according to the general procedure B. The product was obtained as a colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm 4.2 (dq, J = 6. and 3.0 Hz, 1H, CHCH 3 ), 4.02 (dt, J = 9.8 and 3.3 Hz, CH), 1.99-1.91 (m, 1H, CH 2 CH), 1.81-1.2 (m, 1H, CH 2 CH), 1.60 (d, J = 6. Hz, 3H, CH 3 CH), 1.41-1.31 (m, 4H), 0.93 (t, J = 6.8 Hz, 1H, CH 3 ). 13 C NMR (100 MHz, CD 3 ) δ ppm 66.2 (CH), 60.0 (CH), 33.6 (CH 2 ), 31.1 (CH 2 ), 26.3 (CH 2 ), 22.4 (CH 2 ), 20. (CH 3 ), 13.9 (CH 3 ). IR ν max (CH 3 solution): 2929, 2861, 1456, 1381. CO 2 Et (+)-Ethyl 9,10-dichlorooctadecanoate 4i Ethyl 8-(3-octyloxiran-2-yl)octanoate (22 mg, 0.00 mmol) was treated according to the general procedure B. The product was obtained as a colorless oil (15 mg, 66% yield). 1 H NMR (400 MHz, CD 3 ) δ ppm 4.13 (q, J =.2 Hz, 2H, CO 2 CH 2 ), 4.03 (dd, J = 8.8, 3.6 Hz, 2H, CHCH), 2.30 (t, J =.6 Hz, 2H, CH 2 CO 2 Et), 1.33-1.25 (m, 29H), 0.89 (t, J = 6.4 Hz, 3H, CH 2 CH 2 CH 3 ). 13 C NMR (68 MHz, CD 3 ) δ ppm 3 A. Bongini, G. Cainelli, M. Contento and F. Manescalchi, J. Chem. Soc., Chem. Commun., 1980, 128-129. S8

14.0 (Cq), 65. (CH), 65. (CH), 60.3 (CH 2 ), 34.5 (CH 2 ), 34.5 (CH 2 ), 34.4 (CH 2 ), 31.9 (CH 2 ), 30.2 (CH 2 ), 29.5 (CH 2 ), 29.3 (CH 2 ), 29.1 (CH 2 ), 29.1 (CH 2 ), 28.9 (CH 2 ), 26.8 (CH 2 ), 26. (CH 2 ), 25.0 (CH 2 ), 22. (CH 2 ), 14.4 (CH 3 ), 14.2 (CH 3 ). IR ν max (CH 3 solution): 292, 285, 13, 15, 1464, 133, 1302, 124, 1182, 1119, 1098, 1036, 50, 24, 64. HRMS: [M + Na] + C 20 H 38 2 O 2 Na, found 403.213, theoretical mass 403.2141. Synthesis of dichlorolipid (CO) 2, Ph 3PO (cat.) C 6H 3N t Bu 2, C 6D 6, 80 C, 25 h, 66% CO 2 H H 2SO 4 (cat.), EtOH 80 C, 19 h, 8% 4i CO 2 Et mcpba, DCM CO 2 Et O r.t., 16 h, 96% CO 2 Et 8 LiOH, 1:1 THF/MeOH r.t., 6 h, 1% 9 CO 2 H CO 2 Et Elaidic acid ethyl ester Elaidic acid (282 mg, 1 mmol) was dissolved in ethanol (2.0 ml) and concentrated sulfuric acid (2 drops) added then heated at 80 C. After 19 h the solution was cooled to r.t., diluted with Et 2 O and washed with saturated NaHCO 3 solution. The organic phase was dried over MgSO 4 and concentrated by rotary evaporator to give the crude product. The crude was purified by column chromatography over silica gel (petroleum ether/ Et 2 O: 1/1) which gave the compound (269 mg, 8% yield) as a colorless oil. 1 H NMR (20 MHz, CD 3 ) δ ppm 5.40-5.3 (m, 2H, CHCH), 4.13 (q, J =.0 Hz, 2H, COOCH 2 CH 3 ), 2.29 (t, J =.6 Hz, 2H, CH 2 COOEt), 2.00-1.94 (m, 4H, CH 2 CHCHCH 2 ), 1.6-1.5 (m, 2H, CH 2 CH 2 COOEt), 1.40-1.23 (m, 23H), 0.89 (t, J = 6.5 Hz, 3H, CH 2 CH 2 CH 3 ). 13 C NMR (68 MHz, CD 3 ) δ ppm 14.0 (Cq), 130.6 (CH), 130.3 (CH), 60.2 (CH 2 ), 34.5 (CH 2 ), 32. (CH 2 ), 32.6 (CH 2 ), 32.0 (CH 2 ), 29. (CH 2 ), 29. (CH 2 ), 29.6 (CH 2 ), 29.4 (CH 2 ), 29.3 (CH 2 ), 29.2 (CH 2 ), 29.2 (CH 2 ), 29.0 S9

(CH 2 ), 25.1 (CH 2 ), 22.8 (CH 2 ), 14.4 (CH 3 ), 14.2 (CH 2 ). HRMS: [M+Na] + C 20 H 38 O 2 Na, found 333.25, theoretical mass 333.264. IR ν max (thin film): 2925, 2854, 139, 1465, 1180, 96. O CO 2 Et (±)-Ethyl 8-(3-octyloxiran-2-yl) octanoate 8 Elaidic acid ethyl ester (241 mg, 0.8 mmol) was diluted with dichloromethane (5.0 ml) and meta-chloroperbenzoic acid (269 mg, 1.56 mmol) added and stirred at r.t. for 16 h. The resulting suspension was diluted with Et 2 O and washed with 10% Na 2 S 2 O 3 solution, brine, then saturated NaHCO 3 solution. The combined aqueous phases were extracted with Et 2 O then the combined organic phase was dried over MgSO 4 and concentrated by rotary evaporator to give the crude product. The crude was purified by column chromatography over silica gel (petroleum ether/ Et 2 O: 9/1) which gave the compound (244 mg, 96% yield) as a colorless oil. 1 H NMR (20 MHz, CD 3 ) δ ppm 4.13 (q, J = 4.1 Hz, 2H, COOCH 2 CH 3 ), 2.6-2.63 (m, 2H, CH(O)CH), 2.29 (t, J =.6 Hz, 2H, CH 2 COOEt), 1.64-1.23 (m, 29H), 0.88 (t, J = 5.1 Hz, CH 2 CH 2 CH 3 ). 13 C NMR (68 MHz, CD 3 ) δ ppm 13.9 (Cq), 60.3 (CH 2 ), 59.0 (CH), 59.0 (CH), 34.4 (CH 2 ), 32.2 (CH 2 ), 32.2 (CH 2 ), 31.9 (CH 2 ), 29.6 (CH 2 ), 29.5 (CH 2 ), 29.3 (CH 2 ), 29.3 (CH 2 ), 29.3 (CH 2 ), 29.1 (CH 2 ), 26.1 (CH 2 ), 25.0 (CH 2 ), 22. (CH 2 ), 14.3 (CH 3 ), 14.2 (CH 3 ). HRMS: [M+Na] + C 20 H 38 O 3 Na, found 349.209, theoretical mass 349.213. IR ν max (thin film): 292, 2856, 13, 1465, 118. CO 2 H (±)-9,10-Dichlorooctadecanoic acid 9 S10

(±)-Ethyl 9-10-dichlorooctadecanoate (129 mg, 0.34 mmol) was diluted with 1:1 THF/MeOH (3.4 ml) then 1 M LiOH solution (2.4 ml, 2.38 mmol) was added and stirred at r.t. for 6 h. The resulting solution was diluted with Et 2 O and acidified to ph 1 with 3 M H. The organic phase was washed with H 2 O then brine and dried over MgSO 4. This was concentrated by rotary evaporator to give the crude product which was purified by column chromatography over silica gel (petroleum ether/et 2 O: 2/1) which gave the compound (85 mg, 1% yield) as white crystals, mp 3-38 C. An analytically pure sample was obtained by recrystallization from n-pentane with cooling to -10 C. 1 H NMR (20 MHz, CD 3 ) δ ppm 4.04 (dd, J = 8.6, 3.5 Hz, 2H, CHCH), 2.36 (t, J =.3 Hz, 2H, CH 2 CO 2 H), 1.94-1.29 (m, 26H), 0.89 (t, J = 6.2 Hz, 3H, CH 2 CH 3 ). 13 C NMR (68 MHz, CD 3 ) δ ppm 180.2 (Cq), 65. (CH), 65.6 (CH), 34.5 (CH 2 ), 34.4 (CH 2 ), 34.1 (CH 2 ), 31.9 (CH 2 ), 29.5 (CH 2 ), 29.3 (CH 2 ), 29.1 (CH 2 ), 29.1 (CH 2 ), 29.0 (CH 2 ), 28.9 (CH 2 ), 26.8 (CH 2 ), 26. (CH 2 ), 24. (CH 2 ), 22. (CH 2 ), 14.2 (CH 3 ). HRMS: [M+Na] + C 1c8 H 34 O 2 2 Na, found 35.1810, theoretical mass 35.1828. IR ν max (thin film): 351, 3011, 2929, 2858, 142, 109, 1466, 1241. Characterization of esters and chlorohydrins OH 2-Chlorododecan-1-ol 6b To a solution of 1,2-epoxydecane (0.22 ml, 1.0 mmol) in CH 3 was added H (2 ml of a 2.0 solution in Et 2 O). The reaction mixture was stirred at room temperature for 2 hours. The mixture was then diluted with Et 2 O and extracted with H 2 O. The organic phase was dried over MgSO 4 and concentrated in vacuo. Purification by flash column chromatography (silica, petroleum ether/ Et 2 O: 4/1) gave the chlorohydrin (62 mg, 28% yield) as colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm 4.08-4.02 (m, 1H, CH), 3.82 (dd, J = 12.0 and 3.6 Hz, 1H, CH 2 OH), 3.69 (dd, J = 12.0 and.1 Hz, 1H, CH 2 OH), 1.99 (br, 1H, OH), 1.82-1.2 (m, 2H), 1.63-1.55 (m, 2H), 1.33-1.24 ( br S11

m, 14H), 0.91 (t, J = 6.8 Hz, 3H). 13 C NMR (100 MHz, CD 3 ) δ ppm 6.0 (CH 2 ), 65.4 (CH), 34.2 (CH 2 ), 31.9 (CH 2 ), 29.5 (CH 2 ), 29.5 (CH 2 ), 29.4 (CH 2 ), 29.3 (CH 2 ), 29.1 (CH 2 ), 26.3 (CH 2 ), 22.6 (CH 2 ), 14.1 (CH 3 ). HRMS: [M+Na] + C 12 H 25 NaO, found 243.1485, theoretical mass 243.1486. IR ν max (CH 3 solution): 3588, 292, 2856, 1466, 1391, 1068. O O O 2-Chlorododecyl 2-chloro-2-oxoacetate 5b To a solution of CO 2 (60 µl, 0.680 mmol) in CD 3 (1.0 ml) was added 2-chlorododecan-1-ol (100 mg, 0.453 mmol). The reaction mixture was stirred at room temperature for 2 hours after which time it was concentrated in vacuo. 1 H NMR (400 MHz, CD 3 ) δ ppm 4.56-4.45 (m, 2H, CH 2 O), 4.19-4.13 (m, 1H, CH), 1.91-1.3 (m, 2H, CH 2 CH), 1.6-1.54 (m, 1H), 1.53-1.42 (m, 1H), 1.36-1.2 (br m, 14H), 0.91 (t, J = 6.8 Hz, 3H). 13 C NMR (100 MHz, CD 3 ) δ ppm 160.5 (Cq), 155.2 (Cq), 1.0 (CH 2 ), 5. (CH), 34.3 (CH 2 ), 31.9 (CH 2 ), 29.5 (CH 2 ), 29.5 (CH 2 ), 29.3 (CH 2 ), 29.3 (CH 2 ), 28.9 (CH 2 ), 25.9 (CH 2 ), 22. (CH 2 ), 14.1 (CH 3 ). HRMS (of the CH 3 OH derived methyl ester): [M+Na] + C 15 H 2 NaO 4, found 329.1492, theoretical mass 329.1490. IR ν max (CH 3 solution): 2941, 192, 1465, 1263. OH 1-Chlorododecan-2-ol 6a To a solution of 1,2-epoxydecane (0.22 ml, 1.0 mmol) in CH 3 was added H (2 ml of a 2.0 solution in Et 2 O). The reaction mixture was stirred at room temperature for 2 hours. The mixture was then diluted with Et 2 O and extracted with H 2 O. The S12

organic phase was dried over MgSO 4 and concentrated in vacuo. Purification by flash column chromatography (silica, petroleum ether/ Et 2 O: 4/1) gave the chlorohydrin (22 mg, 10% yield) as colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm 3.85-3.80 (m, 1H, CHOH), 3.66 (dd, J = 11.0 and 3.2 Hz, 1H, CH 2 ), 3.50 (dd, J = 11.0 and.2 Hz, 1H, CH 2 ), 2.14 (s, 1H, OH), 1.61-1.42 (m, 4H), 1.34-1.24 (br m, 14H), 0.90 (t, J = 6.8 Hz, 3H). 13 C NMR (100 MHz, CD 3 ) δ ppm 1.4 (CH), 50.6 (CH 2 ), 34.2 (CH 2 ), 31.9 (CH 2 ), 29.5 (2 CH 2 ), 29.5 (CH 2 ), 29.5 (CH 2 ), 29.3 (CH 2 ), 25.5 (CH 2 ), 22.6 (CH 2 ), 14.1 (CH 3 ). HRMS: [M+Na] + C 12 H 25 NaO, found 243.148, theoretical mass 243.1486. IR ν max (CH 3 solution): 3585, 2928, 2856, 1466, 1254, 1042. O O O 1-Chlorododecan-2-yl 2-chloro-2-oxoacetate 5a To a solution of CO 2 (60 µl, 0.680 mmol) in CD 3 (1.0 ml) was added 1-chlorododecan-2-ol (100 mg, 0.453 mmol). The reaction mixture was stirred at room temperature for 2 hours after which time it was concentrated in vacuo. 1 H NMR (400 MHz, CD 3 ) δ ppm 5.25-5.19 (m, 1H, CHO), 3.4-3.66 (m, 2H, CH 2 ), 1.85-1.6 (m, 2H), 1.43-1.23 (br m, 16H), 0.91 (t, J = 6.8 Hz, 3H). 13 C NMR (100 MHz, CD 3 ) δ ppm 160. (Cq), 155.2 (Cq), 8. (CH), 44.5 (CH 2 ), 31.8 (CH 2 ), 31.4 (CH 2 ), 29.5 (CH 2 ), 29.4 (CH 2 ), 29.2 (2 CH 2 ), 29.1 (CH 2 ), 24.8 (CH 2 ), 22.6 (CH 2 ), 14.1 (CH 3 ). HRMS (of the CH 3 OH derived methyl ester): [M+Na] + C 15 H 2 NaO 4, found 329.1492, theoretical mass 329.1490. IR ν max (CH 3 solution): 2928, 2856, 166, 145, 1180. S13

OH O Ph Si Ph (+)-1-(tert-butyldiphenylsilyloxy)-3-chlorohexan-2-ol 2 6d To a solution of tert-butyldiphenyl((3-propyloxiran-2-yl)methoxy)silane (354 mg, 1.00 mmol) in CH 3 (1.0 ml) was added H (0.60 ml of a 2.0 M solution in Et 2 O). The reaction mixture was stirred for 2 hours at room temperature. The mixture was then diluted with Et 2 O and extracted with H 2 O. The organic phase was dried over MgSO 4 and concentrated in vacuo. Purification by flash column chromatography (silica, petroleum ether/ Et 2 O: 4/1) gave the chlorohydrin (360 mg, 92% yield) as colorless oil. 1 H NMR (400 MHz, CD 3 ) δ ppm.0-.6 (m, 4H, H Ar ),.4-.40 (m, 6H, H Ar ), 4.2-4.23 (m, 1H, CHOH), 3.82-3.1 (m, 3H, CH+CH 2 OTBDPS), 2.24 (d, J = 6.6 Hz, 1H, OH), 1.86-1.80 (m, 2H), 1.53-1.43 (m, 2H), 1.09 (s, 9H, tbu), 0.9 (t, J =.4, Hz, 3H). 13 C NMR (100 MHz, CD 3 ) δ ppm 135.55 (d, J = 5.1 Hz, 2 CH), 133.02 (d, J = 9.6 Hz, Cq), 129.89 (CH), 12.81 (d, J = 2.4 Hz, 2 CH), 3.6 (CH), 64.8 (CH 2 ), 64.4 (CH), 36.6 (CH 2 ), 26.8 (3 CH 3 ), 19.9 (CH 2 ), 19.2 (Cq), 13.4 (CH 3 ). HRMS: [M+NH 4 ] + C 22 H 35 NO 2 Si, found 408.2136, theoretical mass 408.2120. IR ν max (CH 3 solution): 3562, 303, 3011, 2962, 2860, 141, 1428, 1112, 823. O O O O Ph Si Ph (+)-1-(tert-butyldiphenylsilyloxy)-3-chlorohexan-2-yl 2-chloro-2-oxoacetate 5d To a solution of (CO) 2 (0.1 ml, 1.15 mmol) in CD 3 (1.5 ml) was added (+)-1-(tert-butyldiphenylsilyloxy)-3-chlorohexan-2-ol (300 mg, 0.68 mmol). The S14

mixture was heated at 50 o C for 24 hours. The mixture was concentrated in vacuo. 1 H NMR (400 MHz, CD 3 ) δ ppm.1-.65 (m, 4H, H Ar ),.49-.40 (m, 6H, H Ar ), 5.30-5.2 (m, 1H, CHO), 4.26-4.21 (m, 1H, CH), 3.98-3.89 (m, 2H, CH 2 OTBDPS), 1.8-1.9 (m, 1H), 1.-1.69 (m, 1H), 1.66-1.59 (m, 1H), 1.53-1.46 (m, 1H), 1.0 (s, 9H, tbu), 0.96 (t, J =.3 Hz, 3H). 13 C NMR (100 MHz, CD 3 ) δ ppm 160.5 (Cq), 155.1 (Cq), 135.53 (d, J = 11.6 Hz, 2 CH), 132.45 (d, J = 11.6 Hz, Cq), 130.08 (d, J = 3. Hz, CH), 12.94 (d, J = 1.5 Hz, 2 CH), 80. (CH), 62.4 (CH 2 ), 59.5 (CH), 35.9 (CH 2 ), 26.6 (3 CH 3 ), 19.9 (Cq), 19.4 (CH 2 ), 13.3 (CH 3 ). HRMS (of the CH 3 OH derived methyl ester): [M+Na] + C 25 H 33 NaO 5 Si, found 499.1686, theoretical mass 499.168. IR ν max (CH 3 solution): 2963, 2860, 160, 1428, 1261, 1113. NMR Spectra of dichloride products 4a, 400 MHz, CD 3 S15

4a, 100 MHz, CD 3 4b, 400 MHz, CD 3 S16

4b, 100 MHz, CD 3 4c, 400 MHz, CD 3 S1

4c, 100 MHz, CD 3 4e, 400 MHz, CD 3 S18

4e, 100 MHz, CD 3 4d, 400 MHz, CD 3 S19

4d, 100 MHz, CD 3 4g, 400 MHz, CD 3 S20

4g, 100 MHz, CD 3 4f, 400 MHz, CD 3 S21

4f, 100 MHz, CD 3 4h, 400 MHz, CD 3 S22

4h, 100 MHz, CD 3 4i, 20 MHz, CD 3 S23

4i, 68 MHz, CD 3 0.909 0.860 1.233 0.885 1.259 CO 2 Et, 20 MHz, CD 3 5.39 5.403 5.32 5.366 5.384 4.168 4.089 2.316 2.261 1.663 1.56 1.269 1.286 2.000 1.96 1.93 1.958 1.620 1.64 1.596 1.363 4.142 4.116 2.289 1.300 2.01 2.00 2.08 4.21 2.4 23.2 3.49.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) S24

14.013 130.55 130.312 60.239 31.994 29.029 32.69 34.4 29.24 25.02 22.2 14.346 14.208 29.205 CO 2 Et, 68 MHz, CD 3 168 160 152 144 136 128 120 112 104 96 88 80 2 64 56 48 40 32 24 16 Chemical Shift (ppm) 0.902 0.85 1.231 0.883 1.25 1.284 O CO 2 Et 1.31 8, 20 MHz, CD 3 4.166 4.08 4.140 4.113 2.668 2.633 2.652 2.316 2.260 2.288 1.643 1.606 1.520 1.434 1.483 1.499 1.90 1.95 2.00 28.98 3.15.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) S25

O CO 2 Et 8, 68 MHz, CD 3 13.944 60.254 58.948 59.001 31.925 34.423 32.208 32.185 29.602 29.106 26.134 26.03 25.003 22.42 14.338 14.1 29.305 168 160 152 144 136 128 120 112 104 96 88 80 2 64 56 48 40 32 24 16 Chemical Shift (ppm) 0.913 0.864 1.28 1.34 CO 2 H 0.890 9, 20 MHz, CD 3 1.943 1.16 4.062 4.049 4.030 4.01 2.389 2.334 1.923 1.908 1.892 1.855 1.803 1.60 1.644 1.618 1.590 1.52 2.361 1.96 2.00 26.1 3.0.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) S26

28.869 26.99 24.659 22.34 14.185 29.106 CO 2 H 9, 68 MHz, CD 3 65.68 65.610 34.4 34.439 29.465 31.910 180.193 34.09 16 168 160 152 144 136 128 120 112 104 96 88 80 2 64 56 48 40 32 24 16 Chemical Shift (ppm) NMR Spectra of esters and chlorohydrins 6b, 400 MHz, CD 3 S2

6b, 100 MHz, CD 3 5b, 400 MHz, CD 3 S28

5b, 100 MHz, CD 3 6a, 400 MHz, CD 3 S29

6a, 100 MHz, CD 3 5a, 400 MHz, CD 3 S30

5a, 100 MHz, CD 3 6d, 400 MHz, CD 3 S31

6d, 100 MHz, CD 3 5d, 400 MHz, CD 3 S32

5d, 100 MHz, CD 3 S33