Supporting Information

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1 Supporting Information Copper-Catalyzed Asymmetric Borylative Ring Opening of Diazabicycles Hyesu Lee, Jung Tae Han, and Jaesook Yun* Department of Chemistry and Institute of Basic Science Sungkyunkwan University, Suwon , Republic of Korea Table of content 1. General information S2 2. Experimental Details S2 3. Determination of absolute configuration S11 4. References S H and 13 C NMR S14 S1

2 General Information CuCl, NaOt-Bu, pinacolborane, Bis(pinacolato)diboron were purchased from Aldrich and used as received. 1a 1c, 1 1d, 2 1e, 3 (pin)b SiMe 2 Ph 4 and (pin)b B(dan) 5 were prepared according to the literature procedures.tetrahydrofuranwas distilled from sodiumbenzophenoneketyl under nitrogen. All reactions were carried out with standard Schlenk technique. Flash chromatography was performed on silica gel from Merck ( mesh). Thin layer chromatography (TLC) was performed on glass plates coated with silica gel 60 with F254 indicator and visualization was accomplished with UV light and/or p-anisaldehyde followed by heating. Infrared spectra (IR) were obtained on Nicolet 205FTIR and are recorded in cm -1. High performance liquid chromatography (HPLC) was performed using Younglin Acme 9100 series. All 1 H NMR spectra were obtained on Varian Mercury 300 and 500 systems reported in parts per million (ppm) downfield from tetramethylsilane. 13 C NMR spectra are reported in ppm referenced to deuteriochloroform (77.16 ppm). Optical rotation was measured with Model 343 plus polarimeter equipped with a sodium lamp source (589 nm). High resolution mass spectra (HRMS) were obtained at Sogang Center for Research Facilities of Sogang University or at Korea Basic Science Institute (Daegu, Korea) and reported in the form of m/z (intensity relative to peak = 100). Ring opening of bicyclic hydrazine 1a with heteroatom nucleophiles (Scheme 1). Diisopropyl-1-(cyclopent-3-enyl)hydrazine dicarboxylate (2) A mixture of CuTC (2.9 mg, mmol, 3 mol %)and dppbz (6.7 mg, mmol, 3 mol %) in anhydrous toluene(1.0 ml) was stirred for 10 min in a Schlenk tube under an atmosphere of nitrogen. Pinacol borane (145μL, 1 mmol, 2 equiv) was added to the reaction mixture and the reaction mixture was stirred for 10 min. 1a (134.2 mg, 0.5 mmol, 1 equiv) in toluene (0.5 ml) was added to the reaction mixture and then it was stirred for 12 hours at room temperature. The reaction was monitored by TLC. Upon completion of the reaction, the mixture was filtered by a pad of Celite and concentrated. The crude product was purified by chromatography on silica gel to afford 2 in 74% yield as white solid. 1 H NMR (500 MHz, CDCl 3 ) δ 6.42 (br s, 1H), 5.65 (s, 2H), (m, S2

3 3H), (m, 2H), 2.46 (br s, 2H), 1.25 (s, 12H); 13 C NMR (125 MHz, CDCl 3 ) δ 156.4, 155.4, 128.8, 69.9, 69.6, 57.3, 35.9, 22.1, 21.9; IR (neat) 3665, 2981, 2866, 1708, 1692, 1055cm -1 ; HRMS (FAB) calcd for [C 13 H 22 N 2 O 4 +H + ] , found Diisopropyl-1-[2-(dimethyl(phenyl)silyl)cyclopent-3-enyl]hydrazine dicarboxylate (4) A mixture of CuCl (1.5 mg, mmol, 3 mol %), dppbz (6.7 mg, mmol, 3 mol %) and NaOt-Bu (9.6 mg, 0.1 mmol, 20 mol %) in anhydrous tetrahydrofuran (0.5 ml) was stirred for 10 min in a Schlenk tube under an atmosphere of nitrogen. Silicon boron (pinb SiMe 2 Ph) (196.7mg, 0.75 mmol, 1.5 equiv) in tetrahydrofuran (0.5 ml) was added to the reaction mixture and the reaction mixture was stirred for 10 min. 1b (148.2 mg, 0.5 mmol, 1 equiv) in tetrahydrofuran (0.5 ml) was added to the reaction mixture and then MeOH (40 μl, 1 mmol, 2 equiv) was added to the reaction mixture. The reaction mixture was stirred for 24 hours at room temperature.the reaction was monitored by TLC. Upon completion of the reaction, the mixture was filtered by a pad of Celite and concentrated. The crude product was purified by chromatography on silica gel to afford 4 in 68% yield as colorless oil. 1 H NMR (500 MHz, CDCl 3 ) δ (m, 2H), (m, 3H), 6.01 (s, 1H), 5.89 (s, 1H), 5.50(s, 1H), 4.89 (brs, 1H), (m, 3H), (m, 18H), 0.33 (s, 3H), 0.31 (s, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 155.6, 154.2, 139.2, 137.7, 133.8, 133.0, 129.5, 129.0, 127.8, 127.7, 81.3, 80.7, 57.7, 38.7, 28.2, 28.1, 0.0, 4.2, 5.0; IR (neat) 2975, 2832, 1747, 1705, 1251, 1032 cm -1 ; HRMS (ESI) calcd for [C 23 H 36 N 2 O 4 Si+Na + ] , found [2-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)cyclopent-3-enyl]di-iso-propylhydrazine dicarboxylate (5) A mixture of CuCl (1.5 mg, mmol, 3 mol %),dppbz (6.7 mg, mmol, 3 mol %) and NaOt-Bu (9.6 mg, 0.1 mmol, 20 mol %) in anhydrous tetrahydrofuran (0.5 ml) was stirred for 10 min in a Schlenk tube under an atmosphere of nitrogen. Heterodiboron (pinb Bdan) (154.3 mg, mmol, 1.05 equiv) in tetrahydrofuran (0.5 ml) was added to the reaction mixture and the reaction mixture was stirred for 10 min. 1a (134.2 mg, 0.5 mmol, 1 equiv) in tetrahydrofuran (0.5 ml) was S3

4 added to the reaction mixture and then MeOH (40 μl, 1 mmol, 2 equiv) was added to the reaction mixture. The reaction mixture was stirred for 24 hours at 80.The reaction was monitored by TLC. Upon completion of the reaction, the mixture was filtered by a pad of Celite and concentrated. The crude product was purified by chromatography on silica gel. 82% yield was determined by crude NMR analysis. Ring opening of diazabicycles with bis(pinacolato)diboron (Scheme 2). General procedure: A mixture of CuCl (1.5 mg, mmol, 3 mol %), (R,R)-taniaphos (15.5 mg, mmol, 4.5 mol %) and NaOt-Bu (2.9 mg, 0.03 mmol, 6 mol %) in anhydrous tetrahydrofuran (0.5 ml) was stirred for 15 min in a Schlenk tube under an atmosphere of nitrogen. Bis(pinacolato)diboron (134 mg, mmol, 1.05 equiv) in tetrahydrofuran (0.5 ml) was added to the reaction mixture and the reaction mixture was stirred for 10 min. Diazabicycles (0.5 mmol, 1 equiv) in tetrahydrofuran (0.5 ml) was added to the reaction mixture and then MeOH (40 μl, 1 mmol, 2 equiv) was added to the reaction mixture. The reaction mixture was stirred for 24 hours at room temperature or 40.The reaction was monitored by TLC. Upon completion of the reaction, the mixture was filtered by a pad celite and concentrated. The crude product was purified by chromatography on silica gel. The ee was determined by HPLC analysis of the corresponding naphthoate derivative obtained by naphthylation. Diisopropyl-1-[(1S,2S)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)cyclopent-3- enyl]hydrazinedicarboxylate (3a) Using the general procedure, the title compound was isolated as colorless oil in 83% yield. 1 H NMR (500 MHz, CDCl 3 ) δ 6.33 (br s, 1H), (m, 2H), (m, 3H), (m, 1H), (m, 1H), 2.30 (br s, 1H), (m, 24H); 13 C NMR (125 MHz, CDCl 3 ) δ 156.3, 155.3, 129.4, 127.9, 83.4, 69.9, 69.5, 59.9, 36.8, 33.7, 24.7, 24.6, 22.1; IR (neat) 3664, 2972, 2923, 1693, 1662, 1055 cm -1 ; HRMS (FAB) calcd for [C 19 H 33 BN 2 O 6 +H + ] , found ; 97% ee was measured by chiral HPLC on an AD-H column (i-proh : hexane = 10 : 90, 0.8mL/min); t R = min (minor), t R = min (major). S4

5 Ditert-butyl-1-[(1S,2S)-2-hydroxycyclopent-3-enyl]hydrazine dicarboxylate (6b) After 1b (148.2 mg, 0.5 mmol, 1 equiv) followed the general procedure of ring opening, a crude mixture of 3b in THF (1.0 ml) and H 2 O (1.0 ml) and NaBO 3 4H 2 O (246.2 mg, 1.6 mmol, 3.2 equiv) was added into a 25 ml round bottom flask and stirred for 2 h at room temperature. The reaction mixture was extracted with CH 2 Cl 2 and then combined organic layers were dried with MgSO 4. After crude mixture was concentrated, it was purified by chromatography on silica gel. The title compound was isolated as colorless solid in 89% yield. 1 H NMR (500 MHz, CDCl 3 ) δ 6.39 (br s, 1H), (m, 2H), 4.95 (s, 1H),4.35 (br s, 1H), 3.33 (s, 1H), 2.56 (s, 1H), 2.42 (br s, 1H), (m, 18H); 13 C NMR (125 MHz, CDCl 3 ) δ 156.3, 155.5, 132.5, 130.4, 81.8, 78.6, 59.6, 57.0, 34.0,28.2, 28.1; IR (neat) 3663, 3007, 2938, 1696, 1653, 1056 cm -1 ; HRMS (FAB) calcd for [C 15 H 26 N 2 O 5 +H + ] , found ; >99% ee was measured by chiral HPLC on an AD-H column (i-proh : hexane = 10 : 90, 1.0 ml/min); t R = min (minor), t R = min (major), [α] D (c 0.63, CHCl 3 ) (lit. 5 [α] D (c 0.8, CHCl 3 ), >99% ee).. Diethyl-1-[(1S,2S)-2-hydroxycyclopent-3-enyl]hydrazine dicarboxylate (6c) After 1c (120.1 mg, 0.5 mmol, 1 equiv) followed the general procedure of ring opening, a crude mixture of 3c in THF (1.0 ml) and H 2 O (1.0 ml) and NaBO 3 4H 2 O (246.2 mg, 1.6 mmol, 3.2 equiv) was added into a 25 ml round S5

6 bottom flask and stirred for 2 h at room temperature. The reaction mixture was extracted with CH 2 Cl 2 and then combined organic layers were dried with MgSO 4. After crude mixture was concentrated, it was purified by chromatography on silica gel. The title compound was isolated as colorless oil in 92% yield. 1 H NMR (500 MHz, CDCl 3 ) δ 6.78 (br s, 1H), (m, 1H), (m, 1H), 4.95 (s, 1H), 4.50 (s, 1H), (m, 4H), 3.31 (br s, 1H), (m, 1H), 2.45 (s, 1H), (m, 6H); 13 C NMR (125 MHz, CDCl 3 ) δ 157.5, 156.6, 132.4, 130.6, 78.4, 69.1, 62.7, 62.4, 33.7, 14.4; IR (neat) 3549, 2982, 2865, 1697, 1657, 1062 cm -1 ; HRMS (FAB) calcd for [C 11 H 18 N 2 O 5 +H + ] , found ; >99% ee was measured by chiral HPLC on an AD-H column (i-proh : hexane = 10 : 90, 1.2 ml/min); t R = min (minor), t R = min (major). Diacetyl-1-[(1S,2S)-2-hydroxycyclopent-3-enyl]hydrazine (6d) After 1d (90.1 mg, 0.5 mmol, 1 equiv) followed the general procedure of ring opening, a crude mixture of 3d in THF (1.0 ml) and H 2 O (1.0 ml) and NaBO 3 4H 2 O (246.2 mg, 1.6 mmol, 3.2 equiv) was added into a 25 ml round bottom flask and stirred for 2 h at room temperature. The reaction mixture was extracted with CH 2 Cl 2 and then combined organic layers were dried with MgSO 4. After crude mixture was concentrated, it was purified by chromatography on silica gel. The title compound was isolated as colorless oil in 62% yield. 1 H NMR (500 MHz, CDCl 3 ) δ (m, 1H), (m, 1H), 4.85 (d, J = 17 Hz, 1H), (m, 1H), 4.25 (br s,1h), 2.71 (s, 1H), (m, 1H), 2.37 (dd, J = 15,0, 8.0 Hz, 1H), (m, 6H); 13 C NMR (125 MHz, CDCl 3 ) δ 174.6, 170.1, 132.1, 131.5, 78.4, 66.7, 33.3, 21.2, 20.7; IR (neat) 3364, 2947, 2834, 1656, 1648, 1025 cm -1 ; HRMS (ESI) calcd for [C 9 H 14 N 2 O 3 +Na + ] , found ; >99% ee was measured by chiral HPLC on an AS-H column (i-proh : hexane = 10 : 90, 1.0 ml/min); t R = min (major), t R = min (minor). S6

7 Benzyl [(1S,2S)-2-hydroxycyclopent-3-enyl]hydroxycarbamate (7) After 1e (115.6 mg, 0.5 mmol, 1 equiv) followed the general procedure of ring opening, a crude mixture of 3e in THF (1.0 ml) and H 2 O (1.0 ml) and NaBO 3 4H 2 O (246.2 mg, 1.6 mmol, 3.2 equiv) was added into a 25 ml round bottom flask and stirred for 2 h at room temperature. The reaction mixture was extracted with CH 2 Cl 2 and then combined organic layers were dried with MgSO 4. After crude mixture was concentrated, it was purified by chromatography on silica gel. The title compound was isolated as colorless solid in 37% yield. 1 H NMR (300 MHz, CDCl 3 ) δ (m, 5H), (m, 2H), 5.12 (s, 2H), 5.08 (s, 1H), 4.75 (s, 1H), (m, 1H), 3.66 (s, 1H), 2.86 (ddd, J = 17.4, 7.5, 2.1 Hz, 1H), 2.14 (ddd, J = 17.4, 7.5, 2.1 Hz, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ 157.5, 136.2, 132.6, 130.6, 128.6, 128.3, 128.2, 83.8, 67.1, 61.2,37.5; IR (neat) 3616, 3004, 2865, 1699, 1653, 1064 cm -1 ; HRMS (ESI) calcd for [(C 13 H 15 NO 4 -O)+Na + ] , found ; >99% ee was measured by chiral HPLC on an AD-H column (i-proh : hexane = 10 : 90, 1.0 ml/min); t R = min (major), t R = min (minor). Benzyl [(1S,2S)-2-hydroxycyclopent-3-enyl]oxycarbamate (8) After 1e (115.6 mg, 0.5 mmol, 1 equiv) followed the general procedure of ring opening, a crude mixture of 3e in THF (1.0 ml) and H 2 O (1.0 ml) and NaBO 3 4H 2 O (246.2 mg, 1.6 mmol, 3.2 equiv) was added into a 25 S7

8 ml round bottom flask and stirred for 2 h at room temperature. The reaction mixture was extracted with CH 2 Cl 2 and then combined organic layers were dried with MgSO 4. After crude mixture was concentrated, it was purified by chromatography on silica gel. The title compound was isolated as orange solid in 11% yield. 1 H NMR (300 MHz, CDCl 3 ) δ 7.50 (s, 1H), (m, 5H), (m, 1H), (m, 1H), 5.19 (s, 2H), 4.94 (s, 1H), 4.46 (ddd, J = 7.5, 4.5, 3.6 Hz, 1H), 2.77 (ddd, J = 17.4, 7.5, 2.1 Hz, 1H), (m, 1H), 2.27 (s, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ 157.9, 135.4, 132.0, 131.4, 128.7, 128.6, 128.4, 93.9, 80.5, 67.8, 35.9; IR (neat) 3548, 2979, 2870, 1702, 1655, 1091 cm -1 ; HRMS (ESI) calcd for [C 13 H 15 NO 4 +Na + ] , found ; >99% ee was measured by chiral HPLC on an AD-H column (i-proh : hexane = 10 : 90, 1.0 ml/min); t R = min (major), t R = min (minor). Addition of allylboronate 3a into various aldehydes (Scheme 4). General procedure 6 : After 1a (134.2 mg, 0.5 mmol, 1 equiv) followed the general procedure of ringopening, a crude mixture of 3a in anhydrous toluene (0.5 ml) was added into a two-neck round bottom flask and stirred for 5 min under an atmosphere of nitrogen at O. Aldehyde (0.75 mmol, 1.5 equiv) was added to the reaction mixture and then it was stirred for 15 h at room temperature. The reaction was monitored by TLC. Upon completion of the reaction, the reaction mixture was quenched with H 2 O (3.0 ml), extracted with CH 2 Cl 2. And thencombined organic layer was dried with MgSO 4. After crude mixture was concentrated, it was purified by chromatography on silica gel. S8

9 Transition state models in the addition of allylic boronate 3a into aldehyde Favored Disfavored Diisopropyl-1-[4-(hydroxy(phenyl)methyl)cyclopent-2-enyl]hydrazine dicarboxylate (9a) Using the general procedure, the title compound was isolated as colorless oil in 74% yield. 1 H NMR (500 MHz, CDCl 3 ) δ (m, 4H), (m, 1H), 6.25 (br s, 1H), 5.72 (s, 1H), 5.64 (s, 1H), 5.39 (brs, 1H), (m, 2H), 4.51 (d, J = 6 Hz, 1H), 3.20 (s, 1H), (m, 2H), 1.85 (s, 1H), (m, 12H); 13 C NMR (125 MHz, CDCl 3 ) δ 156.4, 155.3, 143.1, 136.0, 131.5, 128.3, 127.6, 126.3, 76.9, 70.0, 69.6, 53.1, 31.6, 29.7, 22.1, 21.9; IR (neat) 3650, 2981, 2861, 1683, 1672, 1056 cm -1 ; HRMS (FAB) calcd for [C 20 H 28 N 2 O 5 +H + ] , found ; 9a was protected with acetic anhydride and its ee was measured (95% ee) by chiral HPLC on an OD- H column (i-proh : hexane = 10 : 90, 0.5 ml/min); t R = min (major), t R = min (minor). Diisopropyl-1-[4-(hydroxy(4-nitrophenyl)methyl)cyclopent-2-enyl]hydrazinedicarboxylate (9b) Using the general procedure, the title compound was isolated as colorless oil in 64% yield. 1 H NMR (500 MHz, CDCl 3 ) δ 8.20 (d, J = 8.5 Hz, 2H), 7.52 (d, J = 8.5 Hz, 2H), 6.29 (s, 1H), (m, 1H), (m, 1H), 5.40 (br s, 1H), (m, 2H), 4.71 (s, 1H), 3.21 (s, 1H), 2.74 (br s, 1H), 2.13 (s, 1H), 1.93 (s, 1H), (m, 12H); 13 C NMR (125 MHz, CDCl 3 ) δ 156.4, 155.3, 150.5, 147.2, 135.0, 132.7, 127.1, 123.5, 75.3, 70.2, 69.8, 53.1, 29.7, 29.3, 22.0, 21.9; S9

10 IR (neat) 3654, 2981, 2866, 1691, 1688, 1056 cm -1 ; HRMS (FAB) calcd for [C 20 H 27 N 3 O 7 +H + ] , found Diisopropyl-1-[4-(hydroxy(p-tolyl)methyl)cyclopent-2-enyl]hydrazinedicarboxylate (9c) Using the general procedure, the title compound was isolated as colorless oil in 60% yield. 1 H NMR (500 MHz, CDCl 3 ) δ 7.20 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.20 (br s, 1H), (m, 2H), 5.37 (br s, 1H), (m, 2H), 4.48 (d, J = 6 Hz, 1H), 3.19 (s, 1H), 2.34 (s, 3H), 2.17 (br s, 1H), 2.07 (br s, 1H), 1.78 (s, 1H), (m, 12H); 13 C NMR (125 MHz, CDCl 3 ) δ 156.5, 155.4, 140.1, 137.2, 136.1, 131.4, 129.0, 128.3, 76.9, 70.0, 69.6, 53.1, 31.6, 29.7, 22.1, 22.0, 21.1; IR (neat) 3633, 2979, 2869, 1693, 1678, 1051 cm -1 ; HRMS (FAB) calcd for [C 21 H 30 N 2 O 5 +H + ] , found Diisopropyl-1-[4-(1-hydroxypentyl)cyclopent-2-enyl]hydrazine dicarboxylate(9d) Using the general procedure, the title compound was isolated as yellow oil in 65% yield. The diastereomeric ratio was determined as 2.2:1 by 1 H NMR analysis of crude reaction mixture. 1 H NMR (500 MHz, CDCl 3 ) δ 6.19 (s, 1H), (m, 2H), 5.37 (br s, 1H), (m, 2H), 3.57 (s, 1H), 2.93 (s, 1H), (m, 2H), (m, 1H), (m, 6H), (m, 12H), 0.91 (t, J = 7.0 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 156.5, 155.4, 136.4, 131.4, 73.4, 70.0, 69.6, 51.3, 34.9, 31.6, 29.7, 28.1, 22.7, 22.1, 21.9, 14.0; IR (neat) 2965, 2864, 1740, 1718, 1032 cm -1 ; HRMS (ESI) calcd for [C 18 H 32 N 2 O 5 +Na + ] , found Diisopropyl-1-[4-(1-hydroxy-2-methylpropyl)cyclopent-2-enyl]hydrazine dicarboxylate (9e) Using the general procedure, the title compound was isolated as colorless oil in 74% yield. 1 H NMR (500 MHz, CDCl 3 ) δ 6.32 (br s, 1H), (m, 2H), 5.38 (brs, 1H), (m, 2H), 3.25 (s, 1H), 3.06 (s, 1H), 2.15 (br s, 1H), 2.00 (br s, 1H), (m, 1H), 1.52 (br s, 1H), S10

11 (m, 12H), 0.98 (d, J = 7.0 Hz, 3H), 0.92 (d, J = 7.0 Hz, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 156.3, 155.2, 136.6, 131.4, 78.3, 70.0, 69.5, 48.7, 31.8, 29.7, 22.1, 21.9, 19.6, 17.8; IR (neat) 3679, 2973, 2832, 1724, 1654, 1031 cm -1 ; HRMS (FAB) calcd for [C 17 H 30 N 2 O 5 +H + ] , found Potassium[5-(1,2-bis(tert-butoxycarbonyl)hydrazinyl)cyclopent-2-enyl]trifluoroborate (10) (Scheme 5). The reaction was conducted according to a reported procedure. 7 Excess KHF 2 (234.3 mg, 3 mmol, 6 equiv) was diluted in H 2 O in (1.0 ml). After stirring for 5 minutes, a crude mixture of 3b in 5.0 ml of acetone was added. The mixture was stirred 1 hour at room temperature. The solvents were evaporated in vacuo, adding acetone periodically for azeotropic removal of H 2 O. Once the mixture was evaporated to dryness, it was washed four times with hot acetone. The hot acetone fractions were filtered using gravity filtration and were concentrated in vacuo. The resultant solid was washed with hexane and diethyl ether to afforded white solid in 58% yield. 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.46 (br s, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 2H), (m, 19H); 13 C NMR (125 MHz, DMSO-d 6 ) δ 155.9, 154.6, 137.3, 121.5, 78.8, 58.7, 38.0, 28.6, 28.5, 28.3; IR (neat) 3666, 3006, 2922, 1697, 1685, 1056, 1006 cm -1 ; HRMS (FAB) calcd for [C 15 H 25 BF 3 KN 2 O 4 +K + ] , found Determination of absolute configuration of 3b (Scheme 5). Tert-butyl ((1S,2S)-2-hydroxycyclopentyl)carbamat (11) After 1b (296.4 mg, 1.0mmol, 1 equiv) followed the general procedure of ringopening and oxidation, the subsequent reactions were performed by reported procedures. 8,9 A crude mixture of 6b in dichloromethane (5.0 ml), acetic anhydride (142μL, 1.5mmol, 1.5 equiv) and DMAP (24.4 mg, 0.2mmol, 20 mol %) was added into vial and stirred for 1 h at room temperature. The reaction mixture was treated S11

12 with water and extracted with dichloromethane. The combined organic layers were dried over MgSO 4 and the solvent was evaporated in vacuo. The resulting crude in MeOH (2.0 ml) was added to Pd/C (10.6 mg, 0.1mmol, 10 mol %) under H 2 (1 atm). The solution was stirred for 1 h at room temperature. The mixture was filtered by a pad of Celite and concentrated. The crude product 12 was purified by chromatography on silica gel. Following the reported procedure, the product 12(215.1 mg, 0.6 mmol, 1 equiv) was diluted in 2.5 ml EtOH in a 25 ml round bottom flask, to which was added Raney nickel 2800 in suspension in 0.8 ml EtOH (834 mg of slurry 50 % in water, pre-washed with 2 x 2 ml water, 2 x 2 ml MeOH, 1 x 2 ml EtOH). The reaction mixture was filtered on celite, washed with MeOH. Solvents were removed under reduced pressure, residual MeOH was azeotroped with CH 2 Cl 2. The solution of the crude mixture in a mixture of 1.4-dioxane (2.0 ml) and water (0.1 ml) and 1M NaOH (0.9 ml, 0.9 mmol, 1.5 equiv) was stirred and cooled in an ice bath. Boc 2 O (151.5 μl, 0.66 mmol, 1.1 equiv) was then added to the solution and it was stirred for 6 h at room temperature. 1 M KOH (0.9 ml, 0.9 mmol, 1.5 equiv) was added dropwise to the stirred solution of the crude mixture in THF (1.5 ml) and MeOH (0.6 ml) at 0. After stirring for 30 min at 0, the mixture was allowed to warm to room temperature and Et 2 O was added. The layers were separated and the aqueous layer was extracted with Et 2 O. The combined organic layers were washed with water and brine, dried over Na 2 SO 4 and evaporated under reduced pressure. The crude product was purified by chromatography on silica gel. The product 11 was isolated as white solid in 24% yield from 3b. The characterization data for (1S,2S)-11 was concordant with that already reported in the literature. 13 [α] D = 24.7 (c 0.63, CHCl 3 ) for >99% ee. 1 H NMR (500 MHz, CDCl 3 ) δ 4.73 (br s, 1H), 4.09 (s, 1H), 3.97 (q, J = 6.5 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 2H), 1.45 (s, 9H), (m, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ 157.3, 80.0, 79.8, 60.5, 32.4, 30.4, 28.4, Reference 1. Diels, O.; Bolm, J. H.; Knoll, W. Justus Liebigs Ann. Chem. 1925, 443, Clement, R. A. J. Org. Chem. 1962, 72, Mulvihill, M. J.; Surman, M. D.; Miller, M. J. J. Org. Chem. 1998, 63, Meng, F.; Jang, H.; Hoveyda, A. H. Chem. Eur. J. 2013, 19, S12

13 5. Iwadate, N.; Suginome, M. J. Am. Chem. Soc. 2010, 132, Crotti, S.; Bertolini, F.; Macchia, F.; Pineschi, M. Org.Lett. 2009, 11, Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf, M. R. J. Org. Chem. 1995, 60, Ko, S. H.; Lee, K.-J. Heterocyclic Chem. 2004, 41, Hupe, E.; Marek, I.; Knochel, P. Org. Lett. 2002, 4, Menard, F.; Lautens, M. Angew. Chem. Int. Ed. 2008, 47, Varala, R.; Nuvula, S.; Adapa, S. R. J. Org. Chem. 2006, 71, O Brien, P.; Rosser, C. M.; Caine, D. Tetrahedron 2003, 59, González-Sabín, J.; Morís-Varas, F.; Peña, C.; Rebolledo, F.; Gotor, V. J. Mol. Catal. B: Enzym. 2009, 59, S13

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