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Synlett 2008(12): 1882-1888  
DOI: 10.1055/s-2008-1078505
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient Silver-Mediated Acetalation of β,β′-Functionalized Chlorins

Tillmann Köpke, Maren Pink, Jeffrey M. Zaleski*
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA
Fax: +1(812)8558300; e-Mail: zaleski@indiana.edu;
Further Information

Publication History

Received 3 February 2008
Publication Date:
19 June 2008 (online)

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Abstract

We present a novel synthetic strategy to 2,2-dialkoxy-3-oxochlorins [M = 2H, Ni(II), Cu(II)] (i.e., acetaloxochlorins). Reaction of the corresponding 2,3-dioxochlorin with stoichiometric amounts of silver triflate (AgOTf) in the presence of excess alcohol yields the desired acetaloxochlorins within several hours of reflux in up to 90% yield for n-alcohols, and in 25-89% yields for functionalized alcohol substrates. Similar reaction conditions applied to 2-diazo-3-oxochlorins generates the 2,2-dialkoxy-3-oxochlorins (12-60% yields) accompanied by alkoxyporphyrins (10-27% yields). Electronic spectroscopy reveals for the acetaloxochlorins characteristic π-π* absorption features throughout the visible region and their X-ray crystal structures exhibit marked distortion from planarity of the π-conjugated macrocycle due in part to the steric bulk at the periphery.

Key words

chlorin - silver triflate - acetal - pyrroloquinoline quinine - PQQ

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General Procedure for Isolation of M3 Derivatives from M1: To a solution of dioxochlorin M1 (0.015 mmol) in CH2Cl2-alcohol (1:1.5, 5 mL, a-f respectively), silver triflate (1 equiv) was added and the resulting mixture was stirred under reflux for several hours (Table  [¹] ). After completion of the reaction the mixture was cooled to r.t. and poured into H2O (35 mL). The obtained porphyrinoids were extracted using EtOAc (3 × 10 mL) and the combined organic layers were concentrated under reduced pressure. The crude compounds were purified by silica gel column chromatography using solvent gradients of hexanes, CH2Cl2, and EtOAc.

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Product Characterization Data: Cu3a: MALDI (TOF):
m/z (isotope pattern) = 807.2 [M]. HRMS (ESI): m/z [M + Na+] calcd for C50H40N4O3CuNa: 830.2294; found: 830.2267. UV-Vis (CH2Cl2):λmax = 346, 383, 432, 592, 630 nm. IR: 2961, 2924, 1734, 1599, 1539, 1489, 1441, 1384, 1344, 1319, 1225, 1153, 1086, 1073, 1029, 1009, 995, 791, 752, 700, 502 cm-¹.
Cu3b: MALDI (TOF): m/z (isotope pattern) = 835.4 [M]. HRMS (CI): m/z [M+] calcd for C52H44N4O3Cu: 835.2704; found: 835.2710. UV-Vis (CH2Cl2): λmax = 346, 383, 432, 592, 630 nm. IR: 2960, 2922, 1734, 1599, 1540, 1508, 1489, 1441, 1318, 1233, 1225, 1152, 1091, 1074, 1040, 1009, 995, 890, 833, 791, 752, 710, 700, 502 cm-¹.
Cu3c: MALDI (TOF): m/z (isotope pattern) = 863.4 [M]. HRMS (ESI): m/z [M + Na+] calcd for C54H48N4O3CuNa: 886.2920; found: 886.2905. UV-Vis (CH2Cl2): λmax = 346, 383, 432, 592, 630 nm. IR: 2960, 2928, 2856, 1734, 1599, 1557, 1539, 1508, 1489, 1459, 1441, 1430, 1344, 1319, 1269, 1232, 1150, 1093, 1074, 1026, 1009, 995, 880, 833, 793, 756, 718, 700, 502 cm-¹.
Cu3d: MALDI (TOF): m/z (isotope pattern) = 839.5 [M]. HRMS (CI): m/z [M+] calcd for C50H40N4O5Cu: 839.2289; found: 839.2286. UV-Vis (CH2Cl2): λmax = 347, 388, 435, 595, 635 nm. IR: 2924, 1733, 1598, 1539, 1501, 1489, 1440, 1343, 1318, 1231, 1197, 1151, 1127, 1094, 1072, 1029, 1009, 994, 883, 833, 790, 758, 710, 717, 700, 670, 553, 504 cm-¹.
Cu3e: MALDI (TOF): m/z (isotope pattern) = 849.3 [M + H+]. HRMS (ESI): m/z [M+] calcd for C48H34N4O3Cl2Cu: 848.1377; found: 848.1395. UV-Vis (CH2Cl2): λmax = 347, 388, 435, 595, 635 nm. IR: 2954, 2920, 2851, 1733, 1635, 1598, 1456, 1440, 1384, 1344, 1269, 1230, 1147, 1096, 1070, 1009, 832, 794, 759, 715, 701, 502 cm-¹.
Cu3f: MALDI (TOF): m/z (isotope pattern) = 835.2 [M]. HRMS (CI): m/z [M+] calcd for C52H44N4O3Cu: 835.2704; found: 835.2722. UV-Vis (CH2Cl2): λmax = 346, 383, 432, 592, 630 nm. IR: 2957, 2920, 2870, 1734, 1599, 1541, 1489, 1468, 1365, 1344, 1318, 1232, 1151, 1088, 1073, 1042, 1009, 997, 833, 791, 751, 734, 700, 502 cm-¹.
Ni3b: MALDI (TOF): m/z (isotope pattern) = 830.4 [M]. HRMS (EI): m/z [M+] calcd for C52H44N4O3Ni: 830.2761; found: 830.2735. UV-Vis (CH2Cl2): λmax = 344, 386, 435, 596, 632 nm. ¹H NMR (400 MHz, CD2Cl2): δ = 8.24-8.30 (m, 3 H, β-pyrrolic H), 8.16 (s, 2 H, β-pyrrolic H), 7.90-7.91 (d, J = 4.0 Hz, 1 H, β-pyrrolic H), 7.72-7.77 (m, 4 H, meso-ArH), 7.34-7.62 (m, 16 H, meso-ArH), 3.35-3.50 (m, 4 H, OCH2R), 1.20-1.35 (m, 4 H, OCH2CH 2R), 1.04-1.16 (m, 4 H, OCH2CH2CH 2R), 0.68-0.71 (t, J = 7.2, 7.6 Hz, 6 H, OCH2CH2CH2CH 3). IR: 2954, 2925, 2868, 1734, 1599, 1552, 1490, 1441, 1365, 1349, 1325, 1177, 1152, 1089, 1070, 1010, 892, 843, 834, 793, 751, 715, 700, 503 cm-¹.
Ni3d: MALDI (TOF): m/z (isotope pattern) = 834.5 [M]. HRMS (CI): m/z [M+] calcd for C50H40N4O5Ni: 834.2347; found: 834.2344. UV-Vis (CH2Cl2): λmax = 345, 388, 436, 597, 634 nm. ¹H NMR (400 MHz, CD2Cl2): δ = 8.34-8.40 (m, 3 H, β-pyrrolic H), 8.26 (s, 2 H, β-pyrrolic H), 8.00-8.02 (d, J = 4.8 Hz, 1 H, β-pyrrolic H), 7.84-7.86 (m, 4 H, meso-ArH), 7.23-7.47 (m, 16 H, meso-ArH), 3.60-3.75 (m, 4 H, OCH 2CH2OCH3), 3.33-3.34 (t, J = 4.8, 4.8 Hz, 4 H, OCH2CH 2OCH3), 3.16 (s, 6 H, OCH2CH2OCH 3). IR: 2950, 2922, 2868, 1733, 1599, 1553, 1490, 1441, 1349, 1325, 1232, 1199, 1152, 1129, 1071, 1007, 888, 843, 793, 751, 715, 700, 502 cm-¹.
Ni3e: MALDI (TOF): m/z (isotope pattern) = 842.5 [M]. HRMS (CI): m/z [M+] calcd for C48H34N4O3Cl2Ni: 842.1356; found: 842.1347. UV-Vis (CH2Cl2): λmax = 347, 388, 438, 598, 637 nm. ¹H NMR (400 MHz, CD2Cl2): δ = 8.34-8.39 (m, 3 H, β-pyrrolic H), 8.26-8.27 (m, 2 H, β-pyrrolic H), 8.06-8.07 (d, J = 4.0 Hz, 1 H, β-pyrrolic H), 7.83-7.88 (m, 4 H, meso-ArH), 7.31-7.32 (m, 2 H, meso-ArH), 7.48-7.66 (m, 14 H, meso-ArH), 3.80-3.85 (m, 4 H, alkoxy-OCH2R), 3.40-3.45 (m, 4 H, alkoxy-OCH2CH 2Cl). IR: 2954, 2922, 2854, 1732, 1599, 1557, 1441, 1384, 1349, 1233, 1210, 1153, 1099, 1071, 1013, 793, 751, 716, 701, 555, 503 cm-¹.
Cu4b: MALDI (TOF): m/z (isotope pattern) = 747.3 [M]. HRMS (CI): m/z calcd for C48H36N4OCu: 747.2180; found: 747.2168. UV-Vis (CH2Cl2): λmax = 417, 537, 578 nm. IR: 2955, 2920, 2851, 1586, 1556, 1537, 1516, 1489, 1440, 1384, 1334, 1302, 1240, 1178, 1155, 1070, 1046, 1036, 1005, 994, 796, 783, 759, 715, 703, 502 cm-¹.
Ni4b: MALDI (TOF): m/z (isotope pattern) = 742.3 [M]. HRMS (CI): m/z [M+] calcd for C48H36N4ONi: 742.2237; found: 742.2217. UV-Vis (400 MHz, CH2Cl2): λmax = 413, 530, 570 nm. ¹H NMR (400 MHz, CD2Cl2): δ = 8.60-8.70 (m, 6 H, β-pyrrolic H), 7.95-8.00 [m, 5 H, (1 H, β-pyrrolic H, 4 H, meso-ArH)], 7.57-7.81 (m, 16 H, meso-ArH), 4.11-4.14 (t, J = 6.0, 6.0 Hz, 2 H, OCH2R), 1.42-1.45 (m, 2 H, OCH2CH 2R), 1.16-1.23 (m, 2 H, OCH2CH2CH 2R), 0.85-0.89 (t, J = 7.2, 7.2 Hz, 3 H, OCH2CH2CH2CH 3). IR: 2954, 2922, 2854, 1588, 1525, 1491, 1455, 1440, 1382, 1350, 1322, 1243, 1212, 1180, 1154, 1070, 1007, 970, 837, 790, 752, 715, 700, 555, 503 cm-¹.
H3e: MALDI (TOF): m/z (isotope pattern) = 787.5 [M+]. HRMS (CI): m/z [M+] calcd for C48H36N4O3Cl2: 786.2184; found: 786.2159. ¹H NMR (400 MHz, CD2Cl2): δ = 8.70-8.71 (d, J = 4.0 Hz, 2 H, β-pyrrolic H), 8.42-8.58 (m, 4 H, β-pyrrolic H), 8.00-8.16 (m, 6 H, β-pyrrolic H), 7.88-7.94 (m, 2 H, meso-ArH), 7.56-7.80 (m, 12 H, meso-ArH), 3.88-3.96 (m, 2 H, alkoxy-OCH2R), 3.68-3.76 (m, 2 H, alkoxy-OCH2R), 3.40-3.50 (m, 4 H, alkoxy-OCH2CH 2Cl), -1.97 (s, 1 H, pyrrolic NH), -2.16 (s, 1 H, pyrrolic NH).

35

General Procedure for Isolation of M3b and M4b Derivatives from M2: Diazo-oxochlorin M2 (0.015 mmol) was dissolved in p-dioxane (2 mL) and n-butanol (b; 8 mL), followed by the addition of silver triflate (1 equiv). The resulting mixture was stirred under reflux for 20 h which resulted in the formation of two new species. After consumption of all starting material the reaction mixture was cooled to r.t. The solution was poured into H2O (35 mL) and the porphyrinoid products were extracted with EtOAc (3 × 10 mL). The solvent of the combined organic layers was evaporated under reduced pressure and the crude compounds were purified by silica gel column chromatography using the eluent hexanes-CH2Cl2 (3:1).

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Isolation of Cu4b from CuOH: [2-Hydroxy-5,10,15,20-tetraphenylporphyrinato]Cu(II) (CuOH, 0.0145 mmol) was dissolved in p-dioxane (2 mL) and reacted with AgOTf (1 equiv) and n-butanol (b, 8 mL) under reflux for 20 h. The resulting mixture was cooled to r.t. and poured into H2O (35 mL). Extraction with EtOAc (3 × 10 mL), subsequent concentration and silica gel column chromatography purification gave Cu4b in 37% yield.

40

Hydrolysis of 2,2-Alkoxy-3-oxochlorin Cu3b to Yield Cu1: Heating of a solution of Cu3b (0.006 mmol) in p-dioxane-n-butanol (1:4) for 2 h at 70 ˚C in the presence of aq HCl (10%, 3 mL) resulted in the formation of dioxochlorin Cu1. The reaction mixture was cooled to r.t., poured into H2O (25 mL), and the green compound was extracted with EtOAc (3 × 10 mL). Cu1 was purified by silica gel column chromatography and isolated in 70% yield.

42

Crystals suitable for X-ray diffraction studies were obtained from slow diffusion of methanol into a CH2Cl2 solution. Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication data CCDC 668819 (Cu1), and CCDC 676199 (Cu3a), CCDC 676200 (Cu3d), CCDC 676201 (H3e). Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033; e-mail: deposit@ccdc.cam.ac.uk].
Crystal data for Cu1: red, 0.18 × 0.18 × 0.12 mm, C44H26N4O2Cu, M = 706.23, tetragonal, a = 15.231 (5) Å, b = 15.231 (5) Å, c = 13.452 (7) Å, α = β = γ = 90˚, V = 3121 (2) ų, T = 120 (2) K, space group I42d, Z = 4, ρ calcd = 1.503 Mgm-³, µ = 0.749 mm-¹, 2θmax = 53˚, Mo-Kα (λ = 0.71073). A total of 12518 reflections were measured, of which 1609 (R int = 0.0722) were unique. Final residuals were R1 = 0.0312 and wR2 = 0.0756 [for 1480 observed reflections with I > 2σ(I), 129 parameters] with GOF 1.088 and largest residual peak 0.224 eÅ-³ and hole -0.262 eÅ-³. Crystal data for H3e: black plate, 0.10 × 0.05 × 0.005 mm, C48.50H37N4O3Cl3, M = 656.72, triclinic, a = 12.5326 (11) Å, b = 13.6716 (8) Å, c = 24.8275 (13) Å, α = 88.026 (2)˚, β = 82.395 (3)˚, γ = 70.255 (3)˚, V = 3968.4 (5) ų, T = 100 (2) K, space group P1, Z = 4, ρcalcd = 1.390 Mgm-³, µ = 0.152 mm-¹, 2θmax = 39˚, λ = 0.49595. A total of 53708 reflections were measured, of which 18775 (R int = 0.0654) were unique. Final residuals were R1 = 0.1176 and wR2 = 0.3112 [for 11771 observed reflections with I > 2σ(I), 1061 parameters] with GOF 1.033 and largest residual peak 1.907 eÅ-³ and hole -1.486 eÅ-³.
Crystal data for Cu3a: black, 0.10 × 0.02 × 0.01 mm, C50H40N4O3Cu, M = 808.40, orthorhombic, a = 24.4909 (14) Å, b = 9.1896 (4) Å, c = 34.6315 (15) Å, α = β = γ = 90˚, V = 7794 (6) ų, T = 120 (2) K, space group Pna21, Z = 8, ρ calcd = 1.378 Mgm-³, µ = 0.329 mm-¹, 2θmax = 39˚, λ = 0. 49595. A total of 68079 reflections were measured, of which 19029 (R int = 0.039) were unique. Final residuals were R1 = 0.0439 and wR2 = 0.1191 [for 17428 observed reflections with I > 2σ(I), 1058 parameters] with GOF 1.165 and largest residual peak 0.615 eÅ-³ and hole -0.985 eÅ-³.
Crystal data for Cu3d: black, 0.10 × 0.01 × 0.005 mm, C50.25H41N4O5.25Cu, M = 848.41, monoclinic, a = 35.9629 (12) Å, b = 9.0840 (4) Å, c = 24.6129 (7) Å, α = 90˚, β = 99.771 (2)˚, γ = 90˚, V = 7924.1 (5) ų, T = 120 (2) K, space group C2/c, Z = 8, ρ calcd = 1.422 Mgm-³, µ = 0.328 mm-¹, 2θmax = 39˚, λ = 0. 49595. A total of 35420 reflections were measured, of which 9407 (R int = 0.0759) were unique. Final residuals were R1 = 0.0439 and wR2 = 0.1191 [for 7865 observed reflections with I > 2σ(I), 553 parameters] with GOF 1.064 and largest residual peak 0.755 eÅ-³ and hole
-1.432 eÅ-³.