Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 215 Supporting Information: Diversity-riented Synthesis of Acyclic ucleosides via Ring-pening of Vinyl Cyclopropanes with Purines Hong-Ying iu,* a,b Cong Du, a Ming-Sheng Xie, a Yong Wang, a Qian Zhang, a Gui-Rong Qu, a and Hai-Ming Guo* a a Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan ormal University, Xinxiang 4537, P. R. China b School of Chemistry and Chemical Engineering, Henan Institute of Science and Technology, Xinxiang 4533, China. E-mail: niu_hy@163.com; guohm518@hotmail.com Contents 1. General information...s2 2. General procedure for the 1,5-ring-opening reaction of Pd 2 (dba) 3 CH 3...S2 3. General procedure for the 1,3-ring-opening reaction of Al 3...S2 4. General procedure for the 1,3-ring-opening reaction of MgI 2...S3 5. Hydrogenation of adduct 3aa and 5aa...S3 6. Proposed mechanism for Pd-catalyzed ring-opening reaction...s4 7. Control experiment and proposed mechanism for Al-catalyzed ring-opening reaction......s5 8. Control experiment and proposed mechanism for Mg-catalyzed ring-opening reaction. S5 9. Characterization of compounds...s6 1. References...S21 11. Copies of 1 H MR and 13 C MR spectra...s22 S1
1. General information: All reactions were carried out in oven-dried Schlenk tube filled nitrogen, and monitored by thin layer chromatography (TLC). All reagents were reagent grade quality and purchased from commercial sources unless otherwise indicated. Anhydrous dioxane was freshly distilled from sodium/ benzophenone before used. MR spectra were recorded with a 4 MHz spectrometer for 1 H MR, 1 MHz for 13 C MR. Chemical shifts δ are given in ppm relative to tetramethylsilane as internal standard. Multiplicities are reported as follows: singlet(s), doublet(d), doublet of doublets(dd), triplet(t), quartet(q), multiplet(m). High resolution mass spectra were taken with a 3 mass spectrometer, using Waters Q-TofMS/MS system. For column chromatography silica gel (2-3 mesh) was used as the stationary phase. 1c 1, 1d-f 2, 1g-h 3, 1m 4, 2a-e 5 were synthesized following reported methods. 2. General procedure for the 1,5-ring-opening reaction of Pd 2 (dba) 3 CH 3 : Scheme S1 General procedure for the 1,5-ring-opening reaction of Pd 2 (dba) 3 CH. To an oven-dried Schlenk tube equipped with a magnetic stir bar, was added 2-vinylcyclopropane-1,1-dicarboxylic acid diethyl ester 2a (.1 mmol, 21.2 mg), 6-chloropurine 1a (.15 mmol, 23.2 mg), Pd 2 (dba) 3 CH 3 (5.2 mg, 5 mol%), DIP (5. mg, 1 mol%). The Schlenk tube sealed with threaded stopper was evacuated and backfilled with 2 (this process was repeated for 3 times), and then dioxane (2. ml) were added via syringe. The mixture stirred at 3 o C for 18 h, it was then filtered through Celite and concentrated under vacuum. The resulted residue was purified by flash chromatography over silica gel (ethyl acetate / petroleum ether) to give the desired product 3aa (82 %). 3. General procedure for the 1,3-ring-opening reaction of Al 3 : S2
Scheme S2 General procedure for the 1,3-ring-opening reaction of Al 3. To an oven-dried Schlenk tube equipped with a magnetic stir bar, was added 2-vinylcyclopropane-1,1-dicarboxylic acid diethyl ester 2a (.3 mmol, 63.6 mg), 6-chloropurine 1a (.1 mmol, 15.5 mg), Al 3 (.1 mmol, 13.4 mg). The Schlenk tube sealed with threaded stopper was evacuated and backfilled with 2 (this process was repeated for 3 times), and then dioxane (2. ml) were added via syringe. The mixture stirred at 85 o C for 18 h, it was then filtered through Celite and the organic phase was washed with cooled water. The organic layer was dried over anhydrous a 2 S 4, filtered and concentrated under vacuum. The resulted residue was purified by flash chromatography over silica gel (ethyl acetate / petroleum ether) to give the desired product 5aa (79 %). 4. General procedure for the 1,3-ring-opening reaction of MgI 2 : Scheme S3 General procedure for the 1,3-ring-opening reaction of MgI 2. To an oven-dried Schlenk tube equipped with a magnetic stir bar, was added 2-vinylcyclopropane-1,1-dicarboxylic acid diethyl ester 2a (.5 mmol, 16.1 mg), 6-chloropurine 1a (.1 mmol, 15.5 mg), MgI 2 (2.8 mg, 1 mol%). The Schlenk tube sealed with threaded stopper was evacuated and backfilled with 2 (this process was repeated for 3 times), and then dioxane (2. ml) were added via syringe. The mixture stirred at 85 o C for 18 h, it was then filtered through Celite and the organic phase was washed with cooled water. The organic layer was dried over anhydrous a 2 S 4, filtered and concentrated under vacuum. The resulted residue was purified by flash chromatography over silica gel (ethyl acetate / petroleum ether) to give the desired product 6aa (72 %). 5. Hydrogenation of adduct 3aa and 5aa. Scheme S4 Hydrogenation of adduct 3aa. S3
To a solution of acyclic nucleoside analogue 3aa (11. mg,.3 mmol) in MeH (1. ml) at ºC, abh 4 (68. mg, 1.8 mmol) was added. After 3aa was consumed (determined by TLC), saturated H 4 aq. (1. ml) was added. The aqueous phase was extracted with CH 2 2 (1. ml 3) and the combined organic phases were dried and concentrated. The residue was purified by silica gel flash chromatography (CH 2 2 /MeH) to afford product 7aa (53 %). Scheme S5 Hydrogenation of adduct 5aa. To a solution of acyclic nucleoside analogue 5aa (11. mg,.3 mmol) in MeH (1. ml) at ºC, abh 4 (68. mg, 1.8 mmol) was added. After 5aa was consumed (determined by TLC), saturated H 4 aq. (1. ml) was added. The aqueous phase was extracted with CH 2 2 (1. ml 3) and the combined organic phases were dried and concentrated. The residue was purified by silica gel flash chromatography (CH 2 2 /MeH) to afford product 8aa (47 %). 6. Proposed mechanism for Pd-catalyzed ring-opening reaction A possible catalytic cycle for the palladium-catalyzed 1,5-ring-opening of vinyl cyclopropane 2a with 6-chloro-purine 1a was shown in Scheme S6. Initially, palladium () coordinated with the vinyl cyclopropane 2a to genarate the zwitterionic π-allylpalladium complex A by cleavage of the three-membered ring. Subsequently, the proton transfer from the 6-chloro-purine 1a to intermediate A afforded nucleophilic anions C and D. The anion C attacked the less substituted carbon of the π-allyl moiety in intermediate B will produce the 1,5-ring-opening 9-adduct 3aa. Meanwhile, the nucleophilic addition between anion D with less substituted carbon of intermediate B will generate 1,5-ring-opening 7 adduct 4aa. If the anions C or D attacted the more substituted carbon of the intermediate B, the 1,3-ring-opening 9 adduct 5aa and 7 adduct 6aa will be obtained, respectively. S4
Et Et 2a L L Pd (A) Et Et 1a H PdL 2 Et Et 3aa L L Pd (B) Et + Et (C) (D) Scheme S6 The proposed mechanism for the palladium-catalyzed ring-opening reaction 7. Control experiment and proposed mechanism for Al-catalyzed ring-opening reaction The control experiment with 6-nitro-benzoimidazole 1s as a nucleophilie was carried out in the presence of Al 3, and the 1,3-ring-opening products were afforded in 82% total yield, in which the ratio of the 1 to 3 adducts was 45:37 (Scheme S7a). Thus, we proposed that the 3 in purine participated in the coordination with aluminium and resulted in the high regioselectivity. 6 As shown in Scheme S7b, the bidentate vinyl cyclopropane 2a and 3 in 6-chloro-purine 1a coordinated with aluminium to form complex E. Thus, the 9 position was close to vinyl cyclopropane 2a to procced with 1,3-ring-opening reaction to generate the 1,3-ring-opening 9-adduct 5aa. a) b) 3 3 Et 2 1 H 1s 2 1 + Al 3 (1. equiv) 3 + dioxane, 85 o C 2 Et 1 Et Et Et 5sa, 45% yield 5sa':37% yield 2a 9 Al H Et 9-attack + 3 Et Et 9 3 3 H Al Al 3 1a 2a Et 7 (E) 7 Et Et Et 5aa Scheme S7 (a) The control experiment; (b) The proposed mechanism for the aluminium-catalyzed ring-opening reaction. 8. Control experiment and proposed mechanism for Mg-catalyzed ring-opening reaction The control experiments with 6-chloro-benzoimidazole 1t as nucleophiles was explored, and the corresponding 1,3-ring-opening products were obtained in a poor ratio of 1 to 3 adducts S5
(Scheme 8a). Thus, we proposed that the 3 in purine also participated in the coordination with magnesium and resulted in the high regioselectivity. 7 As shown in Scheme 8b, the bidentate vinyl cyclopropane 2a and bidentate 3, 9 in 6-chloro-purine 1a coordinated with magnesium to form an octahedral geometry as the intermediate F. Thus, the 7 position could attack vinyl cyclopropane 2a to afford the 7-adduct 6aa. Scheme S8 (a) The control experiment; (b) The proposed mechanism for the magnesium-catalyzed ring-opening reaction 9. Characterization of compounds (E)-Diethyl 2-(4-(6-chloro-9H-purin-9-yl)but-2-en-1-yl)malonate (3aa) Colorless oil; 82% yield. 1 H MR (4 MHz, CD 3 ): δ 8.75 (s, 1H), 8.12 (s, 1H), 5.88-5.75 (m, 2H), 4.84 (d, J = 5.2 Hz, 2H), 4.21-4.14 (m, 4H), 3.42 (t, J = 7.2 Hz, 1H), 2.68 (t, J = 6.4 Hz, 2H), 1.24 (t, J = 6.8 Hz, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.3, 151.7, 151.4, 15.7, 144.7, 132.7, 131.3, 125.5, 61.4, 51., 45.4, 31., 13.9 ppm. HRMS: calcd for C 16 H 19 4 4 a [M+a] + 389.987, found 389.987. S6
(E)-Dimethyl 2-(4-(6-chloro-9H-purin-9-yl)but-2-en-1-yl)malonate (3ab) Colorless oil; 82% yield. 1 H MR (4 MHz, DMS): δ 8.78 (s, 1H), 8.63 (s, 1H), 5.83-5.76 (m, 1H), 5.67-5.6 (m, 1H), 4.85 (d, J = 6. Hz, 2H), 3.63 (t, J = 7.6 Hz, 1H), 3.58 (s, 6H), 2.49 (m, 2H) ppm. 13 C MR (1 MHz, DMS): δ 169.3, 152.1, 152., 149.5, 147.6, 131.2, 131.1, 127.1, 52.8, 5.8, 45.6, 31.3 ppm. HRMS: calcd for C 14 H 15 4 4 a [M+a] + 361.674, found 361.677. (E)-Diisopropyl 2-(4-(6-chloro-9H-purin-9-yl)but-2-en-1-yl)malonate (3ac) i i Pr Pr 3ac Colorless oil; 75% yield. 1 H MR (4 MHz, CD 3 ): δ 8.75 (s, 1H), 8.12 (s, 1H), 5.88-5.74 (m, 2H), 5.7-4.98 (m, 2H), 4.83 (d, J = 5.6 Hz, 2H), 3.34 (t, J = 7.2 Hz, 1H), 2.65 (t, J = 6.4 Hz, 2H), 1.21 (t, J = 3.2 Hz, 12H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168., 152., 151.6, 151., 144.8, 133.1, 131.6, 125.4, 69.2, 51.5, 45.6, 31.1, 21.6, 21.5 ppm. HRMS: calcd for C 18 H 23 4 4 a [M+a] + 417.13, found 417.131. (E)- Di-tert-butyl 2-(4-(6-chloro-9H-purin-9-yl)but-2-en-1-yl)malonate (3ad) t t Bu Bu 3ad Colorless oil; 56% yield. 1 H MR (4 MHz, CD 3 ): δ 8.75 (s, 1H), 8.13 (s, 1H), 5.87-5.74 (m, 2H), 4.84 (d, J = 5.2 Hz, 2H), 3.22 (t, J = 7.2 Hz, 1H), 2.59 (t, J = 6.4 Hz, 2H), 1.42 (s, 18H) ppm. 13 C MR (1 MHz, CD 3 ): δ 167.9, 152., 151., 144.8, 133.4, 125., 81.8, 53.1, 45.7, 31.2, 27.9 ppm. HRMS: calcd for C 2 H 27 4 4 a [M+a] + 445.1613, found 445.166. S7
(E)-Bis(2,2,2-trifluoroethyl) 2-(4-(6-chloro-9H-purin-9-yl)but-2-en-1-yl)malonate (3ae) CH 2 CF 3 CH 2 CF 3 3ae Colorless oil; 37% yield. 1 H MR (4 MHz, CD 3 ): δ 8.75 (s, 1H), 8.9 (s, 1H), 5.88-5.72 (m, 2H), 4.85 (d, J = 5.6 Hz, 2H), 4.53 (q, J = 8. Hz, 4H), 3.67 (t, J = 7.2 Hz, 1H), 2.76 (t, J = 6.8 Hz, 2H) ppm. 13 C MR (1 MHz, CD 3 ): δ 166.1, 152.1, 151.2, 144.7, 13.6, 127.2, 61.3, 6.9, 5.3, 45.4, 31. ppm. HRMS: calcd for C 16 H 13 F 6 4 4 a [M+a] + 497.422, found 497.412. (E)-Dimethyl 2-(4-(6-iodo-9H-purin-9-yl)but-2-en-1-yl)malonate (3bb) I 3bb Me Me Colorless oil; 63% yield. 1 H MR (4 MHz, CD 3 ): δ 8.63 (s, 1H), 8.12 (s, 1H), 5.8 (q, J = 5.3 Hz, 2H), 4.81 (d, J = 4.6 Hz, 2H), 3.72 (s, 6H), 3.46 (t, J = 7.2 Hz, 1H), 2.68 (t, J = 6.2 Hz, 2H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.9, 152., 147.8, 144.1, 138.6, 132.6, 125.8, 122.1, 52.7, 5.9, 45.6, 31.2 ppm. HRMS: calcd for C 14 H 15 I 4 4 a [M+a] + 453.3, found 453.32. (E)-Diethyl 2-(4-(6-(propylthio)-9H-purin-9-yl)but-2-en-1-yl)malonate (3ca) Colorless oil; 92% yield. 1 H MR (4 MHz, CD 3 ): δ 8.69 (s, 1H), 7.91 (s, 1H), 5.81-5.71 (m, 2H), 4.77 (d, J = 4.4 Hz, 2H), 4.22-4.1 (m, 4H), 3.41-3.34 (m, 3H), 2.66 (t, J = 6.4 Hz, 2H), 1.86-1.77 (m, 2H), 1.22 (t, J = 7.2 Hz, 6H), 1.7 (t, J = 7.2 Hz, 3H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.5, 161.6, 151.9, 148.1, 142., 131.9, 131.3, 126.3, 61.6, 51.3, 45., 31.2, 3.6, 22.9, 14., 13.4 ppm. HRMS: calcd for C 19 H 26 4 4 Sa [M+a] + 429.1567, found 429.1569. S8
(E)-Diethyl 2-(4-(2-chloro-6-(pyrrolidin-1-yl)-9H-purin-9-yl)but-2-en-1-yl)malonate (3da) Colorless oil; 67% yield. 1 H MR (4 MHz, CD 3 ): δ 7.63 (s, 1H), 5.77-5.69 (m, 2H), 4.68 (s, 2H), 4.17-4.16 (m, 6H), 3.74 (s, 2H), 3.39 (t, J = 7.2 Hz, 1H), 2.64 (t, J = 6.4 Hz, 2H), 2.6-1.97 (m, 4H), 1.23 (t, J = 7.2 Hz, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.6, 154.2, 153.3, 151.1, 138.6, 131.4, 126.7, 119., 61.5, 51.4, 48.9, 47.7, 44.8, 31.2, 26.1, 24.1, 14. ppm. HRMS: calcd for C 2 H 26 5 4 a [M+a] + 458.1566, found 458.1563. (E)-Diethyl 2-(4-(2-chloro-6-(piperidin-1-yl)-9H-purin-9-yl)but-2-en-1-yl)malonate (3ea) 3ea Et Et Colorless oil; 89% yield. 1 H MR (4 MHz, CD 3 ): δ 7.63 (s, 1H), 5.78-5.66 (m, 2H), 4.66 (d, J = 4.8 Hz, 2H), 4.23-4.141(m, 4H), 3.39 (t, J = 7.2 Hz, 1H), 2.65 (t, J = 6.4 Hz, 2H), 1.7 (s, 6H), 1.23 (t, J = 7.2 Hz, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.6, 154., 153.9, 151.8, 137.8, 131.4, 126.6, 118.5, 61.5, 51.3, 44.8, 31.2, 26.1, 24.6, 14. ppm. HRMS: calcd for C 21 H 28 5 4 a [M+a] + 472.1722, found 472.1728. (E)-Diethyl 2-(4-(2-chloro-6-morpholino-9H-purin-9-yl)but-2-en-1-yl)malonate (3fa) Colorless oil; 89% yield. 1 H MR (4 MHz, CD 3 ): δ 7.66 (s, 1H), 5.73 (dd, J = 7.6, 5. Hz, 2H), 4.68 (d, J = 4.3 Hz, S9
2H), 4.22-4.15 (m, 8H), 3.82 (t, J = 4.8 Hz, 4H), 3.4 (t, J = 7.2 Hz, 1H), 2.7-2.6 (m, 2H), 1.24 (t, J = 7.2 Hz, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.6, 154., 153.9, 152., 138.4, 131.7, 126.5, 118.7, 66.9, 61.6, 51.4, 44.9, 31.2, 14.1 ppm. HRMS: calcd for C 2 H 26 5 5 a [M+a] + 474.1515, found 474.1518. (E)-Dimethyl 2-(4-(6-phenyl-9H-purin-9-yl)but-2-en-1-yl)malonate (3gb) Colorless oil; 67% yield. 1 H MR (4 MHz, CD 3 ): δ 9.2 (s, 1H), 8.77 (d, J = 7.6 Hz, 2H), 8.1 (s, 1H), 7.6-7.51 (m, 3H), 5.87-5.75 (m, 2H), 4.86 (d, J = 4.4 Hz, 2H), 3.71 (s, 6H), 3.47 (t, J = 7.2 Hz, 1H), 2.69 (t, J = 6.4 Hz, 2H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.9, 154.9, 152.4, 152.2, 143.9, 135.6, 131.8, 131., 131., 129.7, 128.6, 126.5, 52.7, 51., 45., 31.3 ppm. HRMS: calcd for C 2 H 2 4 4 a [M+a] + 43.1377, found 43.1371. (E)-Diethyl 2-(4-(6-(phenanthren-9-yl)-9H-purin-9-yl)but-2-en-1-yl)malonate (3ha) Et 3ha Et Colorless oil; 69% yield. 1 H MR (4 MHz, CD 3 ): δ 9.17 (s, 1H), 8.77 (dd, J = 19.6, 8.4 Hz, 2H), 8.27 (s, 1H), 8.22 (d, J = 8. Hz, 1H), 8.11 (s, 1H), 7.98 (d, J = 7.6 Hz, 1H), 7.75-7.55 (m, 4H), 5.92-5.83 (m, 2H), 4.92 (d, J = 3.2 Hz, 2H), 4.23-4.14 (m, 4H), 3.45 (t, J = 7.2 Hz, 1H), 2.71 (t, J = 5.6 Hz, 2H), 1.24 (t, J = 7.2 Hz, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.5, 158., 152.3, 151.9, 144.4, 132.9, 132.3, 131.3, 131.3, 131.1, 13.9, 129.6, 129.6, 128.5, 127.7, 126.8, 126.8, 126.7, 126.5, 126.2, 122.9, 122.6, 61.6, 51.3, 45.2, 31.2, 14.1 ppm. HRMS: calcd for C 3 H 28 4 4 a [M+a] + 531.23, found 531.22. S1
(E)-Diethyl 2-(4-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)but-2-en-1-yl) malonate (3ia) Et Et 3ia Colorless oil; 94% yield. 1 H MR (4 MHz, CD 3 ): δ 7.53 (s, 1H), 5.84-5.73 (m, 2H), 4.87 (d, J = 4. Hz, 2H), 4.21-4.13 (m, 4H), 3.58 (s, 3H), 3.42-3.38 (m, 4H), 2.66 (t, J = 6.4 Hz, 2H), 1.24 (t, J = 7.2 Hz, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.6, 155.2, 151.7, 148.8, 14.5, 132.2, 126.8, 16.8, 61.6, 51.3, 48.3, 31.2, 29.8, 28., 14.1 ppm. HRMS: calcd for C 18 H 24 4 6 a [M+a + ] 415.1588, found 415.1587. (E)-Dimethyl 2-(4-(2-chloro-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)malonate (3jb) Yellow oil; 68% yield. 1 H MR (4 MHz, CD 3 ): δ 7.71-7.69 (m, 1H), 7.3-7.26 (m, 3H), 5.71-5.56 (m, 2H), 4.76 (d, J = 5.2 Hz, 2H), 3.66 (s, 6H), 3.41 (t, J = 7.2 Hz, 1H), 2.64 (t, J = 7.2 Hz, 2H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.9, 141.7, 14.3, 134.8, 13.2, 126.1, 123.2, 122.7, 119.5, 19.6, 52.5, 51.1, 45.8, 31.2 ppm. HRMS: calcd for C 16 H 17 2 4 a [M+a] + 359.769, found 359.763. (E)-Diethyl 2-(4-(4-nitro-1H-imidazol-1-yl)but-2-en-1-yl)malonate (3ka) Yellow oil; 75% yield. 1 H MR (4 MHz, CD 3 ): δ 8. (s, 1H), 7.58 (s, 1H), 5.79-5.68 (m, 2H), 4.91 (d, J = 4.4 Hz, 2H), 4.22-4.14 (m, 4H), 3.39 (t, J = 6.4 Hz, 1H), 2.65 (t, J = 7.2 Hz, 2H), 1.25 (t, J = 7.2 Hz, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.5, 14.7, 133.5, 132.7, 125.9, 61.6, 51.2, 49.4, 31.1, 14. ppm. HRMS: calcd for C 14 H 19 3 6 a [M+a] + 348.1166, found 348.1174. (E)-Diethyl 2-(4-(6-chloro-7H-purin-7-yl)but-2-en-1-yl)malonate (4aa) S11
Colorless oil; 2% yield. 1 H MR (4 MHz, CD 3 ): δ 8.76 (s, 1H), 8.26 (s, 1H), 5.72-5.7 (m, 2H), 5.2 (d, J = 5.2 Hz, 2H), 4.27-4.18 (m, 4H), 3.5 (t, J = 7.2 Hz, 1H), 2.86 (t, J = 6.4 Hz, 2H), 1.28 (t, J = 7.2 Hz, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.7, 151.9, 151.7, 15.9, 145.3, 131.6, 13.9, 125.3, 61.8, 51.1, 4.9, 26.8, 14.1 ppm. HRMS: calcd for C 16 H 19 4 4 a [M+a] + 389.988, found 389.987. Diethyl 2-(2-(6-chloro-9H-purin-9-yl)but-3-en-1-yl)malonate (5aa) Colorless oil; 79% yield. 1 H MR (4 MHz, CD 3 ): δ 8.74 (s, 1H), 8.12 (s, 1H), 6.23-6.22 (m, 1H), 5.38 (d, J = 1.4 Hz, 1H), 5.32-5.28 (m, 2H), 4.23-4.3 (m, 4H), 3.2 (t, J = 7.4 Hz, 1H), 2.73 (t, J = 8. Hz, 2H), 1.26-1.17 (m, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.1, 168.1, 151.8, 151.5, 151., 143.8, 134.1, 131.6, 119.6, 61.9, 61.8, 56.5, 48.6, 32.6, 13.9, 13.8 ppm. HRMS: calcd for C 16 H 19 4 4 a [M+a] + 389.987, found 389.978. Dimethyl 2-(2-(6-chloro-9H-purin-9-yl)but-3-en-1-yl)malonate (5ab) Colorless oil; 87% yield. 1 H MR (4 MHz, CD 3 ): δ 8.74 (s, 1H), 8.12 (s,1h), 6.23-6.14 (m, 1H), 5.38 (d, J = 1.4 Hz, 1H), 5.32-5.28 (m, 2H), 3.73 (s, 3H), 3.63 (s, 3H), 3.24 (t, J = 7.2 Hz, 1H), 2.75 (t, J = 7.6 Hz, 2H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.5, 168.5, 151.9, 151.5, 151.2, 143.8, 134., 131.7, 119.8, 56.5, 52.9, 52.9, 48.3, 32.8 ppm. HRMS: calcd for C 14 H 16 4 4 a [M+a] + 361.674, found 361.664. S12
Diisopropyl 2-(2-(6-chloro-9H-purin-9-yl)but-3-en-1-yl)malonate (5ac) Colorless oil; 67% yield. 1 H MR (4 MHz, CD 3 ): δ 8.73 (s, 1H), 8.13 (s, 1H), 6.23-6.14 (m, 1H), 5.37 (dd, J = 1.4,.7 Hz, 1H), 5.31-5.27 (m, 2H), 5.1-5. (m, 1H), 4.98-4.89 (m, 1H), 3.11 (t, J = 7.2 Hz, 1H), 2.7 (t, J = 7.2 Hz, 2H), 1.24-1.14 (m, 12H) ppm. 13 C MR (1 MHz, CD 3 ): δ 167.8, 167.7, 151.9, 151.5, 151.2, 143.8, 134.2, 131.7, 119.7, 69.7, 69.6, 56.6, 49., 32.6, 21.6, 21.5, 21.5, 21.4 ppm. HRMS: calcd for C 18 H 23 4 4 a [M+a] + 417.13, found 417.1292. Di-tert-butyl 2-(2-(6-chloro-9H-purin-9-yl)but-3-en-1-yl)malonate (5ad) Colorless oil; 63% yield. 1 H MR (4 MHz, CD 3 ): δ 8.74 (s, 1H), 8.13 (s, 1H), 6.23-6.14 (m, 1H), 5.36 (d, J = 1. Hz, 1H), 5.3-5.26 (m, 2H), 2.99 (t, J = 7.2 Hz, 1H), 2.62 (t, J = 7.6 Hz, 2H), 1.45 (s, 9H), 1.39 (s, 9H) ppm. 13 C MR (1 MHz, CD 3 ): δ 167.6, 167.5, 151.9,151.6, 151.2, 143.8, 134.4, 131.8, 119.5, 82.4, 82.4, 56.6, 5.5, 32.8, 27.8, 27.8 ppm. HRMS: calcd for C 2 H 27 4 4 a [M+a] + 445.1613, found 445.165. Dimethyl 2-(2-(6-iodo-9H-purin-9-yl)but-3-en-1-yl)malonate (5bb) Colorless oil; 44% yield. 1 H MR (4 MHz, CD 3 ): δ 8.62 (s, 1H), 8.12 (s, 1H), 6.22-6.14 (m, 1H), 5.39-5.24 (m, 3H), 3.73 (s, 3H), 3.63 (s, 3H), 3.23 (t, J = 7.4 Hz, 1H), 2.74 (t, J = 7.4 Hz, 2H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.6, 168.5, 152., 147.8, 143.1, 138.7, 134., 122.4, 119.8, 56.6, 53., 52.9, 48.3, 32.8 ppm. HRMS: calcd for C 14 H 15 I 4 4 a [M+a] + 453.3, found 453.29. S13
Diethyl 2-(2-(6-ethoxy-9H-purin-9-yl)but-3-en-1-yl)malonate (5la) Colorless oil; 48% yield. 1 H MR (4 MHz, CD 3 ): δ 8.5 (s, 1H), 7.9 (s, 1H), 6.22-6.13 (m, 1H), 5.33-5.21 (m, 3H), 4.66 (q, J = 7.2 Hz, 2H), 4.22-4.3 (m, 4H), 3.17 (t, J = 7.2 Hz, 1H), 2.7 (t, J = 7.4 Hz, 2H), 1.51 (t, J = 7.2 Hz, 3H), 1.21 (dt, J = 19.9, 7.1 Hz, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.4, 168.3, 16.9, 152.1, 151.8, 14.6, 134.8, 121.6, 118.8, 63.1, 61.9, 61.9, 55.8, 48.6, 32.9, 14.5, 14., 13.9 ppm. HRMS: calcd for C 18 H 24 4 5 a [M+a] + 399.1639, found 399.1642. Diethyl 2-(2-(2-chloro-6-(piperidin-1-yl)-9H-purin-9-yl)but-3-en-1-yl)malonate (5ea) Et Et 5ea Colorless oil; 89% yield. 1 H MR (4 MHz, CD 3 ): δ 7.66 (s, 1H), 6.15-6.6 (m, 1H), 5.32-5.21 (m, 2H), 5.19-5.15 (m, 1H), 4.28-4.1 (m, 8H), 3.16 (dd, J = 8., 6.4 Hz, 1H), 2.7-2.51 (m, 2H), 1.72-1.69 (m, 6H), 1.26 (t, J = 7.4 Hz, 3H), 1.19 (t, J = 7.4 Hz, 3H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.4, 168.3, 154., 153.8, 151.9, 136.5, 135., 118.5, 61.9, 61.8, 54.7, 48.6, 33.1, 26.1, 24.6, 13.9, 13.9 ppm. HRMS: calcd for C 21 H 28 5 4 a [M+ a + ] 472.1722, found 472.1713. Diethyl 2-(2-(6-cyclopentyl-9H-purin-9-yl)but-3-en-1-yl)malonate (5ma) Colorless oil; 62% yield. 1 H MR (4 MHz, CD 3 ): δ 8.87 (s, 1H), 8. (s, 1H), 6.24-6.15 (m, 1H), 5.35-5.25 (m, 3H), 4.22-4.14 (m, 2H), 4.11-3.99 (m, 2H), 3.93-3.84 (m, 1H), 3.22 (t, J = 7.2 Hz, 1H), 2.79-2.67 (m, 2H), 2.17-1.76 (m, 8H), 1.23 (t, J = 7.2 Hz, 3H), 1.16 (t, J = 7.2 Hz, 3H) ppm. 13 C MR (1 S14
MHz, CD 3 ): δ 168.4, 168.3, 166.4, 152.5, 15.4, 142., 134.8, 132.3, 119., 61.9, 61.8, 55.7, 48.8, 42.6, 32.8, 32.8, 26.3,14., 13.9 ppm. HRMS: calcd for C 21 H 28 4 4 a [M+a] + 423.23, found 423.1996. Diethyl 2-(2-(6-(phenanthren-9-yl)-9H-purin-9-yl)but-3-en-1-yl)malonate (5ha) 5ha Et Et Colorless oil; 82% yield. 1 H MR (4 MHz, CD 3 ): δ 9.16 (s, 1H), 8.77 (dd, J = 2., 8. Hz, 2H), 8.29-8.25 (m, 2H), 8.12 (s, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.73-7.56 (m, 4H), 6.32-6.24 (m, 1H), 5.44-5.35 (m, 3H), 4.27-4.7 (m, 4H), 3.33 (t, J = 7.2 Hz, 1H), 2.88-2.76 (m, 2H), 1.29-1.2 (m, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.4, 168.3, 158.2, 152.3, 151.9, 143.3, 143.3, 134.6, 132.9, 131.3, 131.2, 131.2, 131., 131., 129.6, 127.8, 126.8, 126.8, 126.7, 126.5, 122.9, 122.6, 119.4, 62., 61.9, 56., 48.8, 32.8, 14., 14. ppm. HRMS: calcd for C 3 H 29 4 4 [M+H] + 59.2183, found 59.2174. Diethyl 2-(2-(1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate 5na Yellow oil; 61% yield. 1 H MR (4 MHz, CD 3 ): δ 7.93 (s, 1H), 7.83-7.8 (m, 1H), 7.42-7.4 (m, 1H), 7.31-7.28 (m, 2H), 6.12-6.4 (m, 1H), 5.35 (dd, J = 1.4, 1.2 Hz, 1H), 5.23 (dd, J = 17.2, 1.2 Hz, 1H), 5.6-5.1 (m, 1H), 4.21-4.3 (m, 4H), 3.18 (dd, J = 8., 6.4 Hz, 1H), 2.73-2.59 (m, 2H), 1.24-1.18 (m, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.6, 168.4, 144., 141.4, 135., 133.1, 123., 122.4, 12.6, 118.7, 11.5, 61.9, 61.8, 56.1, 48.5, 32.6, 14., 13.9 ppm. HRMS: calcd for C 18 H 22 2 4 a [M+a] + 353.1472, found 353.1467. S15
Diethyl 2-(2-(5,6-dimethyl-1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate 5oa Yellow oil; 35% yield. 1 H MR (4 MHz, CD 3 ): δ 7.79 (s, 1H), 7.55 (s, 1H), 7.13 (s, 1H), 6.9-6.1 (m, 1H), 5.3 (dd, J = 1.4, 1.2 Hz, 1H), 5.18 (dd, J = 17.2, 1.2 Hz, 1H), 4.98-4.93 (m, 1H), 4.21-4.5 (m, 4H), 3.16-3.13 (m, 1H), 2.69-2.56 (m, 2H), 2.36-2.35 (m, 6H), 1.23-1.16 (m, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.5, 168.3, 142.4, 14.6, 135.1, 132., 131.4, 131.3, 12.3, 118.2, 11.5, 61.7, 61.7, 55.9, 48.4, 32.4, 2.5, 2.1, 13.8, 13.8 ppm. HRMS: calcd for C 2 H 27 2 4 [M+H + ] 359.1965, found 359.1957 Diethyl 2-(2-(1H-benzo[d][1,2,3]triazol-1-yl)but-3-en-1-yl)malonate 5pa 5pa Et Et Yellow oil; 87% yield. 1 H MR (4 MHz, CD 3 ): δ 8.6 (d, J = 8.4 Hz, 1H), 7.52-7.44(m, 2H), 7.39-7.35 (m, 1H), 6.22-6.14 (m, 1H), 5.5-5.44 (m, 1H), 5.32 (d, J = 1.4 Hz, 1H), 5.23 (dd, J = 16.8,.8 Hz, 1H), 4.2-4.3 (m, 4H), 3.22 (dd, J = 8.4, 6.4 Hz, 1H), 2.96-2.88 (m, 1H), 2.8-2.73 (m, 1H), 1.22-1.17 (m, 6H) ppm. 13C MR (1 MHz, CD3): δ 168.6, 168.4, 146.1, 134.8, 132.5, 127.3, 124.1, 12.1, 118.9, 19.7, 61.7, 61.7, 59.7, 48.4, 32.4, 13.9 ppm. HRMS: calcd for C 17 H 21 3 4 a [M+a]+ 354.1424, found 354.1419. Diethyl 2-(2-(6-nitro-1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate (5sa) Yellow oil; 45% yield. 1 H MR (4 MHz, CD 3 ): δ 8.38 (d, J = 2. Hz, 1H), 8.23 (dd, J = 9.2, 2. Hz,1H), 8.17 (s, 1H), 7.88 (d, J = 8.8 Hz, 1H), 6.13-6.5 (m, 1H), 5.46 (dd, J = 1.4, 1.2 Hz, 1H), 5.31 (dd, J = S16
17.2, 1.6 Hz, 1H), 5.15-5.1 (m, 1H), 4.24-4.9 (m, 4H), 3.2 (t, J = 7.2 Hz, 1H), 2.69 (t, J = 7.6 Hz, 2H), 1.25-1.2 (m, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.3, 168.1, 148.2, 145.8, 143.9, 134.1, 132.5, 12.8, 119.8, 118.3, 17.5, 62.1, 62.1, 56.8, 48.5, 32.7, 13.9, 13.9 ppm. HRMS: calcd for C 18 H 22 3 6 [M+H + ] 354.1424, found 354.1424. Diethyl 2-(2-(5-nitro-1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate (5sa') Et Et 2 5sa' Yellow oil; 37% yield. 1 H MR (4 MHz, CD3): δ 8.73 (d, J = 2. Hz, 1H), 8.24 (dd, J = 8.8, 2. Hz, 1H), 8.11 (s, 1H), 7.52 (d, J = 9.2 Hz,1H), 6.12-6.4 (m,1h), 5.44 (dd, J = 1.4, 1.2 Hz,1H), 5.28 (dd, J = 17.2, 1.2 Hz, 1H), 5.14-5.8 (m, 1H), 4.21-4.7 (m, 4H), 3.2 (t, J = 7.2 Hz, 1H), 2.72-2.59 (m, 2H), 1.22 (q, J = 7.2 Hz, 6H) ppm. 13 C MR (1 MHz, CD3): δ 168.2, 168.2, 144.7, 143.8, 143.2, 137.2, 134., 119.8, 118.8, 117.2, 11.6, 62., 62., 56.7, 48.3, 32.5, 13.9, 13.9 ppm. HRMS: calcd for C 18 H 21 3 6 a [M+a]+ 398.1323, found 398.1323. Diethyl 2-(2-(6-chloro-7H-purin-7-yl)but-3-en-1-yl)malonate (6aa) Colorless oil; 72% yield. 1 H MR (4 MHz, CD 3 ): δ 8.9 (s, 1H), 8.35 (s, 1H), 6.12-6.3 (m, 1H), 5.74 (q, J = 7.2 Hz, 1H), 5.41 (d, J = 1.4 Hz, 1H), 5.22 (d, J = 17.2 Hz, 1H), 4.23-4.5 (m, 4H), 3.31 (t, J = 7.2 Hz, 1H), 2.77-2.68 (m, 2H), 1.25-1.19 (m, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168., 167.9, 161.6, 152.3, 146.9, 142.7, 134.8, 122.1, 119.8, 62.1, 62., 57.3, 48.5, 33.5, 13.8 ppm. HRMS: calcd for C 16 H 19 4 4 a [M+a] + 389.987, found 389.978. Dimethyl 2-(2-(6-chloro-7H-purin-7-yl)but-3-en-1-yl)malonate (6ab) Colorless oil; 84% yield. S17
1 H MR (4 MHz, CD 3 ): δ 8.93(s, 1H), 8.36 (s, 1H), 6.13-6.5 (m, 1H), 5.76 (d, J = 7.6 Hz, 1H), 5.44 (dd, J = 1.4, 1.2 Hz, 1H), 5.25 (dd, J = 17.2, 1.2 Hz, 1H), 3.75 (s, 3H), 3.68 (s, 3H), 3.38 (t, J = 7.2 Hz, 1H), 2.78-2.67 (m, 2H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.4, 168.3, 161.6, 152.5, 146.8, 142.8, 134.7, 122.1, 12., 57.3, 53.1, 53., 48.2, 33.7 ppm. HRMS: calcd for C 14 H 15 4 4 a [M+a] + 361.674, found 361.668. Diisopropyl 2-(2-(6-chloro-7H-purin-7-yl)but-3-en-1-yl)malonate (6ac) Colorless oil; 64% yield. 1 H MR (4 MHz, CD 3 ): δ 8.9 (s, 1H), 8.36 (s, 1H), 6.11-6.3 (m, 1H), 5.76-5.7 (m, 1H), 5.4 (dd, J = 1.4, 1.2 Hz, 1H), 5.2 (dd, J = 16.8, 1.2 Hz, 1H), 5.7-4.91 (m, 2H), 3.24 (t, J = 7.2 Hz, 1H), 2.76-2.63 (m, 2H), 1.22-1.15(m, 12H) ppm. 13 C MR (1 MHz, CD 3 ): δ 167.6, 161.7, 152.5, 146.9, 142.8, 135., 122.2, 119.7, 69.9, 69.9, 57.5, 48.9, 33.4, 21.5, 21.5, 21.4 ppm. HRMS: calcd for C 18 H 23 4 4 a [M+a] + 417.13, found 417.129. Di-tert-butyl 2-(2-(6-chloro-7H-purin-7-yl)but-3-en-1-yl)malonate (6ad) Colorless oil; 41% yield. 1 H MR (4 MHz, CD 3 ): δ 8.9 (s, 1H), 8.36 (s, 1H), 6.1-6.1 (m, 1H), 5.7 (q, J = 7.2 Hz, 1H), 5.38 (dd, J = 1.4,.8 Hz, 1H), 5.17 (dd, J = 17.2,.8 Hz, 1H), 3.15 (t, J = 7.2 Hz, 1H), 2.68-2.59 (m, 2H), 1.44 (s, 3H), 1.4 (s, 3H) ppm. 13 C MR (1 MHz, CD 3 ): δ 167.5, 167.4, 161.7, 152.4, 146.9, 142.9, 135.3, 122.3, 119.5, 82.7, 57.7, 5.5, 33.4, 27.9, 27.8 ppm. HRMS: calcd for C 2 H 27 4 4 a [M+a] + 445.1613, found 445.166. Dimethyl 2-(2-(6-iodo-7H-purin-7-yl)but-3-en-1-yl)malonate (6bb) S18
Colorless oil; 31% yield. 1 H MR (4 MHz, CD 3 ): δ 8.77 (s, 1H), 8.37 (s, 1H), 6.9-6.3 (m, 2H), 5.4 (d, J = 9.2 Hz, 1H), 5.16 (d, J = 15.6 Hz, 1H), 3.75 (s, 3H), 3.65 (s, 3H), 3.39 (t, J = 7.2 Hz, 1H), 2.83-2.71 (m, 2H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.4, 168.4, 159., 152.7, 146.9, 135., 127.6, 119.6, 18.3, 55., 53.2, 53.1, 48.2, 33.5 ppm. HRMS: calcd for C 14 H 15 I 4 4 a [M+a] + 453.3, found 453.23. Dimethyl 2-(2-(2,6-dichloro-7H-purin-7-yl)but-3-en-1-yl)malonate (6qb) Colorless oil; 33% yield. 1 H MR (4 MHz, CD 3 ): δ 8.35 (s, 1H), 6.1-6.1 (m, 1H), 5.68 (q, J = 6.8 Hz, 1H), 5.44 (dd, J = 9.2, 1.2 Hz, 1H), 5.23 (dd, J = 15.6, 1.2 Hz, 1H), 3.73 (s, 3H), 3.68 (s, 3H), 3.35 (t, J = 7.2 Hz, 1H), 2.74-2.69 (m, 2H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.3, 168.3, 163.3, 153.3, 148.1, 143.6, 134.4, 121.4, 12.3, 57.6, 53.2, 53.1, 48.1, 33.6 ppm. HRMS: calcd for C 14 H 14 2 4 4 a [M+a] + 395.284, found 395.277. Diethyl 2-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate (6ra) Yellow oil; 71% yield. 1 H MR (4 MHz, CD 3 ): δ 7.7-7.67 (m, 1H), 7.35-7.33 (m, 1H), 7.23-7.16 (m, 2H), 6.14-6.6 (m, 1H), 5.29 (dd, J = 1.4, 1.2 Hz, 1H), 5.13-5.6 (m, 2H), 4.23-4.6 (m, 2H), 3.98 (q, J = 7.2 Hz, 2H), 3.12-3.1 (m, 1H), 2.84-2.76 (m, 1H), 2.72-2.64 (m, 1H), 2.57 (s, 3H), 1.2 (t, J = 7.2 Hz, 3H), 1.13 (t, J = 7.2 Hz, 3H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.6, 168.3, 151.6, 142.7, 1346, 133.5, 122.1, 122., 119.3, 118., 111.1, 61.8, 61.8, 55.6, 48.5, 31.2, 14.6, 13.9, 13.8 ppm. HRMS: calcd for C 19 H 25 2 4 [M+H + ] 345.189, found 345.18. Diethyl 2-(2-(4-nitro-1H-imidazol-1-yl)but-3-en-1-yl)malonate (6ka) S19
Yellow oil; 95% yield. 1 H MR (4 MHz, CD 3 ): δ 7.79 (s, 1H), 7.48 (s, 1H), 5.99-5.91 (m, 1H), 5.44 (d, J = 1.4 Hz, 1H), 5.3 (d, J = 17.2 Hz, 1H), 4.83-4.77 (m, 1H), 4.23-4.17 (m, 4H), 3.21 (t, J = 7.2 Hz, 1H), 2.53-2.48 (m, 2H), 1.29-1.25 (m, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.1, 168., 135.1, 134.1, 12.4, 117.6, 62.2, 62.2, 59.1, 48.2, 33.4, 14., 14. ppm. HRMS: calcd for C 14 H 219 3 6 a [M+a + ] 348.1166, found 348.1165. Diethyl 2-(2-(6-chloro-1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate (6ta) Yellow oil; 45% yield. 1 H MR (4 MHz, CD 3 ): δ 7.91 (s, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.38 (d, J = 1.2 Hz, 1H), 7.24 (d, J = 1.6 Hz, 1H), 6.1-6.1 (m, 1H), 5.38 (d, J = 1.4 Hz, 1H), 5.24 (d, J = 17.2 Hz, 1H), 5.-4.96 (m, 1H), 4.23-4.7 (m, 4H), 3.15 (t, J = 7.2 Hz, 1H), 2.63 (t, J = 7.2 Hz, 2H), 1.25-1.19 (m, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.5, 168.3, 142.6, 142.2, 134.6, 133.7, 128.9, 123.2, 121.4, 119., 11.6, 62., 61.9, 56.2, 48.5, 32.6, 13.9, 13.9 ppm. HRMS: calcd for C 18 H 22 2 4 a [M+a + ] 387.182, found 387.18. Diethyl 2-(2-(5-chloro-1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate (6ta') 6ta' Et Et Yellow oil; 39% yield. 1 H MR (4 MHz, CD 3 ): δ 7.92 (s, 1H), 7.79 (d, J = 1.6 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 7.24 (s, 1H), 6.1-6.1 (m, 1H), 5.37 (dd, J = 1.4,.8 Hz, 1H), 5.22 (dd, J = 17.2,.8 Hz, 1H), 5.4-4.99 (m, 1H), 4.21-4.5 (m, 4H), 3.18-3.14 (m, 1H), 2.7-2.57 (m, 2H), 1.24-1.18 (m, 6H) ppm. 13 C MR (1 MHz, CD 3 ): δ 168.4, 168.3, 144.8, 142.6, 134.6, 131.7, 128.1, 123.6, 12.3, 119., 111.3, 61.9, 61.9, 56.4, 48.4, 32.5, 14., 13.9 ppm. HRMS: calcd for C 18 H 22 2 4 [M+H + ] 365.1263, found 365.1266. S2
(E)-2-(4-(6-Chloro-9H-purin-9-yl)but-2-en-1-yl)propane-1,3-diol (7aa) Colorless oil; 53% yield. 1 H MR (4 MHz, CD 3 ): δ 8.76 (s, 1H), 8.14 (s, 1H), 5.89-5.7 (m, 2H), 4.87 (d, J = 6.4 Hz, 2H), 3.81-3.77 (m, 2H), 3.69-3.65 (m, 2H), 2.16 (t, J = 7.2 Hz, 4H), 1.88-1.61 (m, 1H) ppm. 13 C MR (1 MHz, CD 3 ): δ 152., 144.9, 135., 131.7, 124.4, 65.3, 46., 41.7, 31. ppm. HRMS: calcd for C 12 H 15 4 2 a [M+a] + 35.776, found 35.776. 2-(2-(6-Chloro-9H-purin-9-yl)but-3-en-1-yl)propane-1,3-diol (8aa) Colorless oil; 47% yield. 1 H MR (4 MHz, CD 3 ): δ 8.74 (s, 1H), 8.19 (s, 1H), 6.2-6.12 (m, 1H), 5.43-5.26 (m, 3H), 3.8-3.64 (m, 4H), 2.46 (d, J = 19.1 Hz, 2H), 2.3-2.16 (m, 2H), 1.58-1.52 (m, 1H) ppm. 13 C MR (1 MHz, CD 3 ): δ 151.8, 151.5, 151.2, 143.9, 135.2, 131.6, 119.1, 64.4, 64.4, 56.3, 38.8, 32.7 ppm. HRMS: calcd for C 12 H 15 4 2 a [M+a] + 35.776, found 35.776. 1. References: [1] H. C. Koppel, D. E. 'Brien and R. K. Robins, J. rg. Chem., 1959, 24, 259. [2] G.-R. Qu, L. Zhao, D.-C. Wang, J. Wu and H.-M. Guo, Green Chem., 28, 1, 287. [3] M. Hocek, D. Hocková and H. Dvořáková, Synthesis, 24, 6, 889. [4] H. Dvořáková, D. Dvořák and A. Ho1ý, Tetrahedron Lett., 1996, 37, 1285. [5] A. T. Parsons, M. J. Campbell and J. S. Johnson, rg. Lett., 28, 1, 2541. [6] (a) Y. Hamashima, D. Sawada, M. Kanai and M. Shibasaki, J. Am. Chem. Soc., 1999, 121, 2641; (b) J. Casas, C. ájera, J. M. Sansano and J. M. Saá, rg. Lett., 22, 4, 2589; (c) Y. Hamashima, D. Sawada, H. ogami, M. Kanai and M. Shibasaki, Tetrahedron, 21, 57, 85; (d) J. Casas, C. ájera, J. M. Sansano and J. M. Saá, Tetrahedron, 24, 6, 1487. S21
[7] (a) M. P. Sibi, K. Itoh and C. P. Jasperse, J. Am. Chem. Soc., 24, 126, 5366; (b) M. P. Sibi, G. Petrovic, and J. Zimmerman, J. Am. Chem. Soc., 25, 127, 239, (c) M. P. Sibi,. Prabagaran, S. G. Ghorpade and C. P. Jasperse, J. Am. Chem. Soc., 23, 125, 11796. S22
11. Copies of 1 H MR and 13 C MR spectra 1 H-MR for 3aa 13 C-MR for 3aa 168.295 151.71 151.395 15.661 144.724 132.636 131.33 125.482 77.318 77. 76.682 61.396 53 8.751 8.117 7.26 5.881 5.866 5.843 5.827 5.818 5.814 5.86 5.791 5.767 5.753 4.844 4.831 4.219 4.29 4.197 4.192 4.18 4.174 4.162 4.156 4.144 4.135 3.437 3.418 3.4 2.698 2.681 2.665 1.596 1.256 1.238 1.221 3 25 2 3aa Et Et 15 1 5 6.9 2.1 1.1 4.1 2.1 1.99 9. 8. 7. 6. 5. 4. 3. 2. 1. 45.428 3.975 13.852 35 3 25 2 3aa Et Et 15 1 5 2 15 1 5 S23
S24 1 H-MR for 3ab. 5. 1. 1 2 3 4 5 6 7 8.784 8.628 5.828 5.813 5.797 5.79 5.775 5.76 5.67 5.653 5.634 5.614 5.597 4.868 4.853 3.647 3.628 3.61 3.579 3.372 2.5 2.494 2. 6. 2.3 13 C-MR for 3ab ppm (f1) 5 1 15 2 5 1 15 2 169.33 152.129 152.45 149.465 147.626 131.242 131.119 127.141 52.761 5.776 45.459 4.58 4.37 4.162 39.953 39.744 39.536 39.328 31.326 Me Me 3ab Me Me 3ab
S25 HSQC for 3ab ppm 2. 2.5 3. 3.5 4. 4.5 5. 5.5 6. 6.5 7. 7.5 8. 8.5 9. 9.5 ppm 4 6 8 1 12 14 16 HMBC for 3ab ppm 2. 2.5 3. 3.5 4. 4.5 5. 5.5 6. 6.5 7. 7.5 8. 8.5 9. ppm 2 4 6 8 1 12 14 16 18 8 2' 3' 1' 5' 4' 4 2 8 1' 2' 3' 4' 5' 4 5 2 8 1' 2' 3' 4' 5' 4 5
oesy for 3ab ppm 2 3 4 5 6 7 8 9 9. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 ppm S26
1 H-MR for 3ac 13 C-MR for 3ac 168.44 151.97 151.576 151.29 144.768 133.74 131.571 125.42 77.317 77. 76.682 69.155 51.527 45.636 31.8 21.617 21.542 8.746 8.122 7.26 5.875 5.859 5.836 5.821 5.88 5.796 5.782 5.757 5.743 5.71 5.55 5.4 5.24 5.8 4.993 4.977 4.84 4.826 3.361 3.342 3.324 2.671 2.654 2.638 1.646 1.217 1.29 1.21 1.194 3ac i i Pr Pr 5 12.2 2.1 2. 2.1 1.99 1. 5.. 5 3ac i i Pr Pr 2 15 1 5 S27
1 H-MR for 3ad 13 C-MR for 3ad 167.89 151.969 151.28 144.831 133.443 125.38 81.838 77.317 77. 76.682 53.73 45.69 31.163 27.887 8.753 8.134 7.26 5.87 5.854 5.84 5.831 5.816 5.85 5.84 5.793 5.785 5.779 5.769 5.768 5.755 5.74 4.844 4.831 3.234 3.215 3.197 2.67 2.59 2.574 1.588 1.419 1.248 5 4 3ad t t Bu Bu 3 2 1 18.1 2. 1.1 1.99 2.1 1.1 1. 5.. 1 3ad t t Bu Bu 5 2 15 1 S28 5
1 H-MR for 3ae 8.754 8.89 7.26 5.881 5.879 5.866 5.842 5.828 5.813 5.792 5.775 5.758 5.736 5.721 5.719 4.859 4.845 4.557 4.536 4.516 4.497 3.689 3.672 3.654 2.773 2.756 2.739 1.62 3 25 2 CH 2 CF 3 CH 2 CF 3 15 3ae 1 5 2. 1.1 4. 2. 2. 1. 5.. 13 C-MR for 3ae 166.129 152.7 151.191 144.671 13.624 127.155 77.317 77. 76.683 61.291 6.922 5.288 45.4 3.949 4 3 CH 2 CF 3 CH 2 CF 3 2 3ae 1 2 15 1 S29 5
S3 1 H-MR for 3bb. 5. 1. 5 1 8.63 8.118 7.26 5.815 5.81 5.79 5.777 4.813 4.82 3.716 3.478 3.46 3.442 2.697 2.681 2.666 1.628 2.2 2.1 6.9 1.1 2.1 13 C-MR for 3bb 5 1 15 2 1 2 3 4 168.862 152.5 147.84 144.64 138.581 132.634 125.817 122.144 77.317 77. 76.682 52.699 5.89 45.562 31.235 I Me Me 3bb I Me Me 3bb
S31 1 H-MR for 3ca 13 C-MR for 3ca 5 1 15 2 5 1 168.524 161.556 151.87 148.93 142.41 131.92 131.36 126.262 77.317 77. 76.682 61.556 51.283 45.26 31.164 3.589 22.85 14.18 13.412. 5. 1. 5 1 8.688 7.914 7.26 5.813 5.81 5.775 5.767 5.762 5.759 5.755 5.746 5.721 5.77 4.775 4.764 4.218 4.2 4.191 4.18 4.173 4.162 4.155 4.144 4.137 4.126 4.117 4.99 3.41 3.391 3.38 3.373 3.362 3.344 2.669 2.655 2.637 1.858 1.839 1.821 1.83 1.784 1.766 1.745 1.239 1.221 191 172 154 1.1 2. 2.1 4.3 3.2 2.9 2. 6.4 3. S Et Et 3ca S Et Et 3ca
S32 1 H-MR for 3da 13 C-MR for 3da 5 1 15 2 1 2 3 4 5 168.577 154.186 153.332 151.77 138.599 131.349 126.678 119.18 77.318 77. 76.682 61.541 51.367 48.893 47.692 44.89 31.184 26.169 24.146 14.45. 5. 5 1 7.634 7.26 5.765 5.726 5.724 5.719 5.78 5.69 4.675 4.172 4.166 4.163 4.157 4.155 3.737 3.45 3.386 3.368 2.656 2.643 2.627 2.6 2.16 1.976 1.965 1.74 1.249 1.232 1.214 2. 2. 6.1 2.1 2.1 4.6 6.5 Et Et 3da Et Et 3da
S33 1 H-MR for 3ea 13 C-MR for 3ea 5 1 15 2-5 5 1 15 2 25 3 35 168.583 153.976 153.859 151.758 137.781 131.393 126.633 118.497 77.318 77. 76.682 61.547 51.356 44.84 31.174 26.8 24.592 14.36. 5. 5 1 15 7.63 7.26 5.778 5.765 5.751 5.74 5.726 5.72 5.711 5.697 5.673 5.658 4.669 4.657 4.229 4.211 4.22 4.193 4.184 4.175 4.166 4.157 4.148 4.139 4.13 4.112 3.47 3.388 3.37 2.66 2.645 2.628 1.74 1.252 1.234 1.216 2. 2. 2. 6. 6.2 8. Et Et 3ea Et Et 3ea
S34 1 H-MR for 3fa. 1. 2. 3. 4. 5. 6. 7. 8. 5 7.66 7.26 5.747 5.735 5.728 5.715 4.689 4.678 4.22 4.211 4.21 4.193 4.184 4.175 4.166 4.157 4.148 3.83 3.818 3.86 3.417 3.398 3.38 2.67 2.656 2.639 1.261 1.243 1.225 2. 2. 8. 4. 2. 6. 13 C-MR for 3fa 5 1 15 2 1 2 3 4 5 6 168.57 153.965 153.935 152. 138.41 131.698 126.452 118.686 77.317 77. 76.683 66.941 61.575 51.354 44.939 31.189 14.61 Et Et 3fa Et Et 3fa
S35 1 H-MR for 3gb. 5. 5 1 9.18 8.779 8.76 8.14 7.584 7.567 7.548 7.523 7.57 7.26 5.868 5.854 5.829 5.817 5.85 5.791 5.767 5.752 4.867 4.856 3.79 3.483 3.465 3.446 2.74 2.689 2.673 1.693 2.1 3.1 2. 2. 6.1 1.1 2. 13 C-MR for 3gb 5 1 15 2 1 2 3 4 168.914 154.879 152.388 152.193 143.89 135.59 131.88 136 13.966 129.728 128.653 126.459 77.318 77. 76.683 52.65 5.985 45.25 31.264 Me Me 3gb Me Me 3gb
S36 1 H-MR for 3ha 13 C-MR for 3ha 5 1 15 2 1 2 3 4 5 168.547 158.39 152.357 151.933 144.358 132.855 132.299 131.323 131.25 131.146 13.948 129.622 129.576 128.527 127.738 126.79 126.763 126.699 126.543 126.178 122.928 122.559 77.317 77. 76.682 61.59 51.38 45.193 31.22 14.56 ppm (f1). 5. 1. 5 1 15 2 8.757 8.736 8.268 8.231 8.211 8.111 7.994 7.975 7.746 7.743 7.725 7.716 7.713 7.78 7.75 7.696 7.678 7.675 7.647 7.645 7.628 7.61 7.68 7.592 7.589 7.571 7.554 7.551 7.26 5.886 5.877 5.867 4.924 4.916 4.226 4.217 4.27 4.199 4.189 4.181 4.171 4.163 4.153 4.144 3.465 3.447 3.428 2.727 2.714 2.7 1.636 126 1243 1225 2.1 4.5 2. 2. 4.1 1.1 2. 6.1 Et Et 3ha Et Et 3ha
S37 1 H-MR for 3ia 13 C-MR for 3ia 5 1 15 2-5 5 1 15 2 25 3 35 168.58 155.92 151.616 148.741 14.42 132.176 126.683 16.776 77.318 77. 76.682 61.514 51.271 48.233 31.136 29.75 27.93 14.1. 1. 2. 3. 4. 5. 6. 7. 8. 5 7.533 7.26 5.837 5.831 5.823 5.819 5.792 5.78 5.764 5.75 5.749 5.746 5.739 5.733 5.725 4.871 4.861 4.214 4.25 4.194 4.188 4.177 4.17 4.159 4.152 4.141 4.132 3.581 3.415 3.398 3.379 2.667 2.655 2.637 1.646 1.257 1.24 1.222 2. 2. 4. 3.1 4. 2. 6.4 Et Et 3ia Et Et 3ia
S38 1 H-MR for 3jb. 5. 1 2 3 4 5 6 7 7.71 7.698 7.694 7.31 7.288 7.276 7.265 5.713 5.7 5.687 5.674 5.661 5.648 5.631 5.615 5.597 5.576 5.559 4.762 4.749 3.662 3.428 3.41 3.391 2.653 2.636 2.618 1.719 2.1 2. 6.1 2. 3.57 13 C-MR for 3jb 5 1 15 2 5 1 15 2 168.914 141.689 14.329 134.777 13.164 126.12 123.177 122.725 119.456 19.68 77.317 77. 76.682 52.543 51.97 45.84 31.21 Me Me 3jb Me Me 3jb
1 H-MR for 3ka 7.998 7.577 7.26 5.789 5.776 5.751 5.743 5.738 5.734 5.73 5.72 5.695 5.681 4.97 4.896 4.222 4.213 4.24 4.2 4.195 4.182 4.177 4.164 4.159 4.155 4.147 4.137 3.412 3.394 3.375 2.671 2.653 2.639 1.267 1.249 1.232 7 6 2 5 3ka Et Et 4 3 2 1 6.16 2. 4. 2. 2. 5.. 13 C-MR for 3ka 168.489 14.711 133.526 132.67 125.895 77.318 77. 76.683 61.635 51.191 49.396 31.141 14.36 2 2 15 3ka Et Et 1 5 2 15 1 5 S39
S4 1 H-MR for 4aa 13 C-MR for 4aa 5 1 15 2 1 2 3 4 5 6 168.681 151.96 151.713 15.93 145.292 131.572 13.94 125.325 77.317 77. 76.682 61.818 51.11 4.924 26.88 14.68. 5. 1. 5 1 15 2 8.756 8.256 7.26 5.725 5.712 5.74 5.697 5.29 5.16 4.267 4.258 4.249 4.241 4.232 4.223 4.25 4.197 4.188 4.179 3.515 3.497 3.479 2.873 2.857 2.841 1.64 1.297 1.279 1.262 2. 2. 4. 2. 6. Et Et 4aa Et Et 4aa
S41 1 H-MR for 5aa 13 C-MR for 5aa 5 1 15 2 5 1 15 2 25 168.15 168.71 151.811 151.474 151.75 143.812 134.61 131.598 119.637 77.318 77. 76.682 61.893 61.837 56.493 48.564 32.616 13.878 13.82. 5. 1. 5 1 8.741 8.12 7.26 6.232 6.215 6.26 6.189 6.172 6.163 6.146 5.392 5.366 5.318 5.31 5.29 5.276 4.229 4.22 4.22 4.188 4.185 4.171 4.154 4.144 4.139 4.129 4.12 4.112 4.94 4.76 4.7 4.52 4.43 4.34 4.25 3.213 3.195 3.177 2.754 2.731 2.714 1.63 1.257 1.24 1.222 126 1189 1171 1.1 4.2 2.3 6.1 2.3 Et Et 5aa Et Et 5aa
S42 1 H-MR for 5ab 13 C-MR for 5ab 5 1 15 2 1 2 3 4 168.541 168.5 151.925 151.515 151.243 143.769 134.1 131.684 119.817 77.318 77. 76.682 56.522 52.939 52.873 48.263 32.758. 5. 1. 5 1 15 8.74 8.115 7.26 6.226 6.28 6.2 6.183 6.166 6.157 6.14 5.394 5.368 5.32 5.29 5.277 3.725 3.632 3.259 3.24 3.222 2.764 2.745 2.726 1.653 1.2 1.1 2.1 3. 3.2 2. Me Me 5ab Me Me 5ab
HSQC for 5ab 2 8 b c c' a e d ppm d e a 4 6 8 1 12 14 16 9.5 9. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. ppm HMBC for 5ab ppm 2 4 6 8 1 12 14 16 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 ppm S43
oesy for 5ab 2 8 b c c' a e d ppm 3 4 5 6 7 8 9 9. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 ppm S44
1 H-MR for 5ac 8.734 8.126 7.26 6.228 6.211 6.22 6.185 6.168 6.159 6.142 5.384 5.382 5.358 5.356 5.312 5.39 5.32 5.282 5.268 5.266 5.98 5.83 5.67 5.51 5.36 5.2 5.5 4.984 4.968 4.953 4.937 4.922 4.96 4.89 3.131 3.112 3.94 2.715 2.695 2.677 1.236 1.222 1.27 1.195 1.18 1.152 1.137 1 5ac i i Pr Pr 5 12.2 2. 1.1 1.1 2. 5.. 13 C-MR for 5ac 167.777 167.714 151.924 151.549 151.27 143.821 134.25 131.74 119.686 77.318 77. 76.683 69.67 69.645 56.587 48.991 32.625 21.587 21.481 21.465 21.446 35 3 5ac i i Pr Pr 25 2 15 1 5-5 2 15 1 S45 5
1 H-MR for 5ad 8.744 8.13 7.26 6.227 6.217 6.21 6.25 6.21 6.194 6.184 6.176 6.167 6.164 6.158 6.151 6.148 6.141 5.375 5.35 5.299 5.273 5.257 3.7 2.989 2.971 2.643 2.624 2.65 1.577 1.45 1.39 5 4 3 5ad t t Bu Bu 2 1 9. 9.1 2. 2. 1.1-1 1. 5.. 13 C-MR for 5ad 167.62 167.513 151.899 151.597 151.192 143.833 134.413 131.752 119.54 82.443 82.398 77.317 77. 76.683 56.62 5.546 32.763 27.871 27.789 7 6 5 4 5ad t t Bu Bu 3 2 1-1 2 ppm (f1) 15 1 5 S46
S47 1 H-MR for 5bb. 5. 1. 5 1 15 2 8.624 8.116 7.26 6.222 6.26 6.25 6.21 6.199 6.197 6.196 6.179 6.162 6.158 6.155 6.137 5.391 5.365 5.317 5.274 5.258 5.241 5.239 3.728 3.633 3.25 3.231 3.212 2.762 2.743 2.725 1.585 1.1 1.4 3.2 3.2 3. 1.1 2.1 13 C-MR for 5bb 5 1 15 2 1 2 3 4 5 168.572 168.529 151.949 147.756 143.91 138.661 134.13 122.373 119.818 77.317 77. 76.683 56.556 52.96 52.92 48.288 32.778 I Me Me 5bb I Me Me 5bb
S48 1 H-MR for 5la. 5. 5 1 15 2 8.496 7.897 7.26 6.215 6.198 6.189 6.172 6.155 6.146 6.129 5.331 5.35 5.252 5.235 5.21 4.684 4.666 4.648 4.631 4.215 4.25 4.197 4.187 4.179 4.169 4.161 4.151 4.129 4.12 4.112 4.12 4.85 4.71 4.53 4.44 4.26 3.186 3.167 3.149 2.72 2.71 2.682 1.694 1.528 1.51 1.493 1.248 1 199 1 181 1 163 3. 2. 4.1 1.1 2. 3. 6. 13 C-MR for 5la 5 1 15 2-5 5 1 15 2 25 3 168.358 168.321 16.861 152.64 151.821 14.564 134.84 121.562 118.842 77.318 77. 76.683 63.144 61.87 61.833 55.831 48.645 32.855 14.515 13.96 13.884 Et Et Et 5la Et Et Et 5la
S49 1 H-MR for 5ea 13 C-MR for 5ea 5 1 15 2 5 1 15 2 25 3 168.434 168.332 153.941 153.81 151.883 136.517 135.22 118.481 77.318 77. 76.682 61.911 61.771 54.71 48.644 33.19 26.71 24.579 13.947 13.87. 5. 1 2 3 4 5 7.66 7.26 6.148 6.132 6.122 6.16 6.89 6.79 6.63 5.318 5.292 5.255 5.211 5.194 5.181 5.169 5.154 4.284 4.266 4.257 4.239 4.221 4.23 4.114 4.15 4.87 4.69 4.51 4.42 4.34 4.24 4.6 3.174 3.158 3.153 3.137 2.71 2.687 2.681 2.665 2.651 2.644 2.63 2.584 2.569 2.56 2.545 2.533 2.524 2.59 1.715 1.76 1.694 1.59 1276 1258 124 1194 1176 1.1 2.2 1.3 8.1 6. 3. 3. 2.5 Et Et 5ea Et Et 5ea
S5 1 H-MR for 5ma 13 C-MR for 5ma 5 1 15 2 1 2 3 4 168.354 168.315 166.432 152.59 15.46 142.41 134.768 132.321 119.13 77.317 77. 76.682 61.892 61.811 55.738 48.761 42.585 32.81 32.753 26.273 13.961 13.89. 5. 1. 1 2 3 4 7.997 6.237 6.211 6.195 5.324 5.312 5.291 5.249 4.225 4.215 4.212 4.26 4.198 4.18 4.17 4.162 4.152 4.143 4.131 4.126 4.113 4.19 4.14 4.95 4.86 4.77 4.68 4.5 4.32 4.23 4.14 4.5 3.996 3.987 3.969 3.928 3.97 3.885 3.864 3.843 3.234 3.216 3.198 2.787 2.77 2.751 2.743 2.734 2.729 2.726 2.712 2.77 2.696 2.694 2.688 2.671 2.24 2.2 2.198 2.195 2.183 2.182 2.173 2.167 2.158 2.153 2.145 2.132 213 284 263 2 4 22 214 212 1988 1977 1975 1971 19 1922 194 1894 1815 183 1794 1783 1777 1764 1 8 1 4 1618 1215 1182 1164 3. 2.1 2. 2. 8.3 3. 3.2 Et Et 5ma Et Et 5ma
1 H-MR for 5ha 9.16 8.76 8.286 8.267 8.247 999 89 7.98 7.749 7.746 7.729 7.721 7.718 7.711 7.78 7.7 7.682 7.68 7.648 7.631 7.613 7.611 7.63 7.61 7.583 7.565 7.563 7.26 6.324 6.37 6.298 6.281 6.264 6.255 6.238 5.435 5.419 5.394 5.388 5.345 4.271 4.262 4.253 4.244 4.235 4.227 4.218 4.29 4.2 4.191 4.175 4.166 4.157 4.148 4.13 4.11 4.92 4.83 4.74 4.65 3.344 3.325 2827 2 1256 1 875 857 853 839 821 818 773 755 678 274 234 7 6 5 4 5ha Et Et 3 2 1 6.2 2. 4.2 3. 4.1 1. 5.. 13 C-MR for 5ha 168.357 168.3 158.189 152.266 151.944 143.324 143.269 134.59 132.937 131.349 131.23 131.152 13.956 13.92 129.582 127.769 126.83 126.775 126.718 126.517 122.934 122.56 119.387 77.318 77. 76.682 61.95 61.886 56.38 48.811 32.827 13.998 13.94 1.1 2.1 2.1 25 2 5ha Et Et 15 1 5 2 15 1 S51 5
S52 1 H-MR for 5na 13 C-MR for 5na 5 1 15 2 5 1 168.57 168.411 143.979 141.444 134.979 133.68 123.26 122.45 12.584 118.663 11.511 77.317 77. 76.682 61.871 61.844 56.137 48.51 32.57 13.957 13.913. 5. 1 2 3 4 5 6 7.797 7.419 7.412 7.41 7.44 7.396 7.386 7.38 7.298 7.29 7.283 7.275 7.26 6.123 6.19 6.97 6.81 6.66 6.54 6.4 5.362 5.359 5.336 5.333 5.251 5.248 5.28 5.25 5.62 5.46 5.27 5.24 5.9 4.231 4.213 4.24 4.186 4.171 4.169 4.154 4.145 4.137 4.128 4.12 4.11 4.92 4.74 4.64 4.56 4.47 4.29 3.198 3.182 3.178 3.161 2.733 2717 2711 2697 2681 2675 2663 26 9 2626 2611 266 259 1239 1194 1176 2. 1.1 4. 2. 6.2 Et Et 5na Et Et 5na
1 H-MR for 5oa 7.793 7.549 7.26 7.127 6.53 6.51 6.37 6.25 6.11 5.312 5.31 5.286 5.284 5.2 5.197 5.157 5.154 4.983 4.968 4.961 4.957 4.953 4.946 4.93 4.28 4.199 4.19 4.181 4.173 4.163 4.154 4.145 4.136 4.127 4.123 4.118 4.114 4.15 4.1 4.96 4.82 4.78 4.64 4.55 4.46 3.163 3.147 3.142 3.126 2.691 2.675 2.668 2.655 2.639 2.636 2.632 2.619 2616 2 1 562 358 348 229 211 198 193 1 5oa Et Et 5 6.1 6.1 2.1 4. 1.1 1.1 1.3 1.1 1.1 5.. 13 C-MR for 5oa 168.535 168.348 142.42 14.646 135.86 132.44 131.43 131.189 12.335 118.217 11.539 77.318 77. 76.682 61.717 61.699 55.892 48.376 32.44 2.538 2.12 13.845 13.797 7 6 5 4 5oa Et Et 3 2 1-1 2 15 1 5 S53
1 H-MR for 5pa 8.53 7.483 7.481 7.466 7.464 7.445 7.443 7.386 7.383 7.369 7.365 7.362 7.348 7.345 7.26 6.222 6.25 6.196 6.179 6.162 6.153 6.136 5.496 5.48 5.472 5.463 5.456 5.44 5.332 5.36 5.255 5.254 5.212 5.211 4.23 4.186 4.176 4.168 4.159 4.139 4.128 4.121 4.11 4.13 4.95 4.92 4.77 4.68 4.6 4.51 4.33 3.238 3.222 3.217 3.21 2.956 2.94 2.933 2.92 2897 2121 1 917 94 881 798 783 777 167 62 1 5pa Et Et 5 6. 4. 2. 5.. 13 C-MR for 5pa 168.592 168.416 146.67 134.778 132.492 127.317 124.55 12.77 118.881 19.745 77.318 77. 76.682 61.747 61.723 59.69 48.386 32.414 13.899 5 4 5pa Et Et 3 2 1 2 15 1 5 S54
1 H-MR for 5sa 8 13 C-MR for 5sa 168.27 168.19 148.17 145.827 143.97 134.137 132.53 12.764 119.831 118.276 17.476 77.317 77. 76.682 8.243 8.237 8.22 8.215 8.173 7.894 7.872 7.26 6.132 6.117 6.16 6.89 6.74 6.63 6.48 5.461 5.457 5.435 5.431 5.335 5.331 5.292 5.288 5.155 5.136 5.12 5.11 4.24 4.231 4.222 4.213 4.22 4.195 4.185 4.181 4.177 4.172 4.167 4.164 4.157 4.154 4.151 4.14 4.136 4.133 4.118 4.115 4.16 4.97 4.88 3.22 3.21 3.183 2.79 2 1 69 671 248 7 6 2 5 5sa Et Et 4 3 2 1 1.1 1.1 1.1 1.1 4.8 1.1 2.1 6.5-1 5.. 62.149 62.83 56.751 48.462 32.684 13.948 13.931 8 7 6 2 5 5sa Et Et 4 3 2 1-1 2 15 1 S55 5
1 H-MR for 5sa' 8.735 8.73 8.252 8.247 8.23 8.225 8.111 7.528 7.55 7.26 6.122 6.17 6.96 6.8 6.64 6.53 6.38 5.45 5.447 5.424 5.421 5.33 5.3 5.26 5.257 5.138 5.121 5.12 5.85 4.214 4.25 4.196 4.187 4.168 4.15 4.145 4.132 4.127 4.115 4.19 4.97 4.88 4.79 4.7 3.218 3.2 3.182 2.727 2.71 2.76 2.691 2.674 2.67 2.666 2.652 2 1 648 629 611 66 246 228 5 4 Et Et 3 2 5sa' 2 1 6.3 2. 4.2 1.1 5.. 13 C-MR for 5sa' 168.234 168.156 144.77 143.794 143.22 137.175 133.975 119.762 118.777 117.23 11.571 77.318 77. 76.682 62.3 61.991 56.68 48.33 32.464 13.98 13.876 15 Et Et 1 2 5sa' 5 2 15 1 5 S56
oesy for 5sa' y ppm Et Et 3 2 5sa' 4 5 6 7 8 9 9. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 ppm S57
S58 1 H-MR for 6aa 13 C-MR for 6aa 5 1 15 2 1 2 3 4 167.963 167.943 161.552 152.325 146.879 142.721 134.818 122.91 119.751 77.318 77. 76.682 62.53 61.984 57.333 48.495 33.479 13.812. 5. 1. 5 1 8.92 8.348 7.26 6.121 6.119 6.14 6.11 6.94 6.77 6.59 6.52 6.36 6.34 5.77 5.753 5.734 5.718 5.426 5.4 5.243 5.2 4.232 4.229 4.226 4.223 4.218 4.28 4.19 4.172 4.153 4.124 4.15 4.9 4.73 4.59 4.54 4.48 3.33 3.312 3.295 2.767 2.747 2.731 2.713 2.695 2.677 1.61 1.247 1185 4.1 2. 6.1 Et Et 6aa Et Et 6aa
S59 1 H-MR for 6ab 13 C-MR for 6ab 5 1 15 2 5 1 15 2 25 168.398 168.342 161.63 152.49 146.81 142.86 134.726 122.144 119.963 77.317 77. 76.682 57.35 53.69 52.992 48.199 33.77. 5. 1. 1 2 3 4 5 6 7 8 8.98 8.345 7.26 6.116 6.1 6.9 6.74 6.57 6.47 6.31 5.765 5.748 5.728 5.711 5.438 5.435 5.412 5.49 5.254 5.251 5.211 5.28 3.732 3.66 3.375 3.357 3.339 2.797 2.779 2.761 2.743 2.725 2.75 2.686 2.668 1.67 1.1 3. 3. 2. Me Me 6ab Me Me 6ab
HSQC for 6ab 8 b a c c' e d ppm d e a 4 6 8 1 c b 12 14 16 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. ppm HMBC for 6ab ppm 2 4 6 8 1 12 14 16 9.5 9. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. 1.5 1..5 ppm S6
1 H-MR for 6ac 1 5 5.. 13 C-MR for 6ac 167.618 161.659 152.457 146.87 142.835 135.26 122.198 119.727 77.318 77. 76.683 69.925 69.881 57.496 48.937 33.399 21.54 21.487 21.449 8.895 8.356 7.26 6.111 6.95 6.85 6.68 6.52 6.42 6.26 5.756 5.739 5.736 5.719 5.72 5.412 5.49 5.386 5.383 5.228 5.224 5.185 5.182 5.65 5.5 5.34 5.18 5.3 4.975 4.959 4.944 4.928 4.912 3.256 3.238 3.22 2.761 2.743 2.725 2.77 2.688 2.67 2.654 2.651 2.633 1.664 1.221 1.215 1.21 1.25 1 2 195 6ac i Pr i Pr 12.1 2. 2.1 4 3 6ac i Pr i Pr 2 1 2 15 1 5 S61
1 H-MR for 6ad 8.898 8.362 7.26 6.96 6.8 6.7 6.54 6.38 6.28 6.12 5.732 5.714 5.695 5.678 5.389 5.387 5.363 5.361 5.193 5.19 5.15 5.148 3.169 3.151 3.133 2.68 2.662 2.644 2.626 2.65 2.589 2.587 1.438 1.45 7 6 6ad t Bu t Bu 5 4 3 2 1 9. 2. 1.1 1.1 1.1 1. ppm (f1) 5.. 13 C-MR for 6ad 167.465 167.399 161.734 152.447 146.865 142.9 135.345 122.28 119.469 82.712 77.317 77. 76.682 57.657 5.493 33.42 27.859 27.815 7 6 5 t Bu t Bu 4 6ad 3 2 1-1 2 15 1 S62 5
S63 1 H-MR for 6bb. 5. 1 2 3 4 8.766 8.37 7.26 6.92 6.74 6.6 6.34 5.413 5.39 5.175 5.136 3.751 3.652 3.45 3.387 3.37 2.832 2.831 2.812 2.85 2.795 2.794 2.777 2.766 2.748 2.729 2.717 2.714 2.711 1.69 2.3 1.1 3.3 3.3 2. 13 C-MR for 6bb 5 1 15 2 1 2 3 4 5 168.415 168.372 159.44 152.667 146.883 134.985 127.639 119.558 18.348 77.317 77. 76.683 55.51 53.235 53.84 48.193 33.488 I Me Me 6bb I Me Me 6bb