Download PDF
Synlett 2011(5): 615-618  
DOI: 10.1055/s-0030-1259545
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Highly Selective Mono-C-allylation of DTPA Pentaethyl Ester

Hisao Nemoto*, Kenji Yatsuzuka, Shin-ya Tamagawa, Naoko Hirao, Masaki Kamiya, Tomoyuki Kawamura
Department of Pharmaceutical Chemistry, Institute of Health Biosciences, Graduate School of The University of Tokushima, Tokushima 770-8505, Japan
Fax: +81(88)6337284; e-Mail: nem@ph.tokushima-u.ac.jp;
Further Information

Publication History

Received 3 December 2010
Publication Date:
11 February 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

A highly selective mono-C-allylation of pentaethyl diethylenetriaminepentaacetate was achieved with allyl bromide and potassium carbonate via a newly developed elaborate procedure based on Stevens rearrangement. It is contrastive that the conservative one-pot procedure gave a complicated mixture.

Key words

MRI - Stevens rearrangement - chelating agent - ­Mizoroki-Heck reaction

    References and Notes

  • 1 Caravan P. Ellison JJ. McMurry TJ. Lauffer RB. Chem. Rev.  1999,  99:  2293 
    CrossrefGoogle Scholar
  • 2a Hanaoka K. Kikuchi K. Terai T. Komatsu T. Nagano T. Chem. Eur. J.  2008,  14:  987 
    Google Scholar
  • 2b Yu K. Hamdan Y. Wan F. Li Y. Huang K. Zhou J. Aust. J. Chem.  2006,  60:  218 
    Google Scholar
  • 2c Broekema M. van Eerd JJEM. Oyen WJG. Corstens FHM. Liskamp RMJ. Boerman OC. Harris TD. J. Med. Chem.  2005,  48:  6442 
    Google Scholar
  • 2d Johannes P, and Ulrich N. inventors; WO  2002059076. 
  • 2e Ge P. Selvin PR. Bioconjugate Chem.  2004,  15:  1088 
    Google Scholar
  • 2f Arano Y. Uezono T. Akizawa H. Ono M. Wakisaka K. Nakayama M. Sakahara H. Konishi J. Yokoyama A. J. Med. Chem.  1996,  39:  3451 
    Google Scholar
  • 3 Deshpande SV. Subramanian R. McCall M. DeNardo SJ. Denardo GL. Meares CF. J. Nucl. Med.  1990,  31:  218 
    Google Scholar
  • 4a Anelli PL. Fedeli F. Gazzotti O. Lattuada L. Lux G. Rebasti F. Bioconjugate Chem.  1999,  10:  137 
    Google Scholar
  • 4b Williams MA. Rapoport H. J. Org. Chem.  1993,  58:  1151 
    Google Scholar
  • 4c Anelli PL. Lattuada L. Lorusso V. Lux G. Morisetti A. Morisini P. Serleti M. Uggeri F. J. Med. Chem.  2004,  41:  3629 
    Google Scholar
  • 4d Corson DT. Meares CF. Bioconjugate Chem.  2000,  11:  292 
    Google Scholar
  • 5 Nemoto H. Cai J. Yamamoto Y. Tetrahedron Lett.  1996,  37:  539 
    CrossrefGoogle Scholar
  • 6a Miller WR, and Falls N. inventors; US  2794044. HN(CH2CN)2 from HCHO, HCN, and NH3:
  • 6b Ansmann A, Benisch C, Funke F, Ohlbach F, and Merger M. inventors; US  0058841. Diethylenetriamine from HN(CH2CN)2 and H2:
  • 6c Singer JJ, Mass W, and Weisberg M. inventors; US  2855428. Compound 5 from diethylenetriamine, HCHO, and HCN:
  • 6d Busch CL, Meier HP, and Cemona A. inventors; WO  83/04020. Compound 1 from 5 via hydrolysis:
  • 7 Keana JF. Mann JS. J. Org. Chem.  1990,  55:  2868 
    CrossrefGoogle Scholar
  • 8 Laurent S. Botteman F. Elst LV. Muller RN. Helv. Chim. Acta  2004,  87:  1077 
    CrossrefGoogle Scholar
  • 9 Deal KA. Motekaitis RJ. Martell AE. Welch MJ. J. Med. Chem.  1996,  39:  3096 
    CrossrefGoogle Scholar
  • 10a Stevens TS. Creighton EM. Gordon AB. MacNicol M. J. Chem. Soc.  1928,  3193 
    Google Scholar
  • 10b Vanecko JA. Wan H. West FG. Tetrahedron  2006,  62:  1043 
    Google Scholar
  • 10c Tayama E. Orihara K. Kimura H. Org. Biomol. Chem.  2008,  6:  3673 
    Google Scholar
  • Studies of the C-migration process were reported:
  • 11a Honda K. Inoue S. Sato K. J. Am. Chem. Soc.  1990,  112:  1999 
    Google Scholar
  • 11b Honda K. Inoue S. Sato K. J. Org. Chem.  1992,  57:  428 
    Google Scholar
  • 11c Honda K. Igarashi D. Asami M. Inoue S. Synlett  1998,  685 
    Google Scholar
  • 11d Workman JA. Garrido NP. Sançon J. Roberts E. Wessel HP. Sweeney JB.
    J. Am. Chem. Soc.  2005,  127:  1066 
    Google Scholar
  • 11e Sweeney JB. Chem. Soc. Rev.  2009,  38:  1027 
    Google Scholar
  • 16a Bräse S., de Meijere A.; Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 2004; Vol 1: 217-315
  • 16b de la Escosura A., Marínez-Diaz M. V., Thorarson P., Rowan A. E., Nolte R. J. M., Torres T.; J. Am. Chem. Soc.; 2003, 125: 12300
  • 16c Trost B. M., Toste F. D.; J. Am. Chem. Soc.; 2003, 125: 3090
  • 16d Jeffery T.; Tetrahedron Lett.; 1994, 35: 3051
  • 17 Preparation of 15: Sakurai M., Washizuka K., Hamashima H., Tomishima Y., Imanishi M., Kayakiri H., Taniguchi K., Takamura F.; WO 2002094770, 2002
  • 18 Analytical Data for Compound 16 Colorless oil. FT-IR (neat): 3627, 3396, 2980, 2367, 2054, 1733, 1699, 1508, 1164, 868, 810, 775 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.10 (s, 4 H, arom.), 4.62-4.52 (m, 1 H, NHBoc), 4.18-4.11 (m, 10 H, 5 × OCH 2CH3), 3.54 (s, 8 H, 4 × NCH 2CO2Et), 3.39-3.33 (m, 3 H, NCHCO2Et and CH 2NHBoc), 2.86-2.56 [m, 12 H, N(CH 2CH 2N)2 and CH 2C6H4CH 2], 1.80-1.56 (m, 4 H, NCHCH 2CH 2), 1.44 [s, 9 H, C(CH 3)3], 1.258 (t, J = 7.2 Hz, 12 H, 4 × OCH2CH 3), 1.250 (t, J = 7.2 Hz, 3 H, OCH2CH 3). ¹³C NMR (100 MHz, CDCl3): δ = 172.9 (C, OC=O), 170.8 (4 × C, OC=O), 155.5 (C, NC=O), 139.9 (C, arom.), 136.0 (C, arom.), 128.4 (2 × CH, arom.), 128.2 (2 × CH, arom.), 78.6 (C, OCMe3), 63.4 (CH, NCHCO2Et), 60.0 (4 × CH2, OCH2CH3), 59.7 (CH2, OCH2CH3), 54.9 (4 × CH2, NCH2CO2Et), 53.4 [2 × CH2, N(CH2 CH2N)2], 50.0 [2 × CH2, N(CH2CH2N)2], 41.5 (CH2, CH2NHBoc), 35.5 (CH2, one of CH2 CH2 CH2C6H4 CH2), 34.9 (CH2, one of CH2 CH2 CH2C6H4 CH2), 29.3 (CH2, one of CH2 CH2 CH2C6H4 CH2), 28.1 (3 × CH3C(CH3)3], 27.9 (CH2, one of CH2 CH2 CH2C6H4 CH2), 14.1 (CH3, OCH2 CH3), 13.9 (4 × CH3, OCH2 CH3). ESI-HRMS: m/z [M + H]+ calcd for C40H67N4O12: 795.4755; found: 795.4746. Analytical Data for Compound 17 Hygroscopic colorless solid. FT-IR (KBr): 3420, 2955, 2361, 1734, 1647, 1636, 1507, 1457, 1418, 1214, 1057, 954, 899, 814, 667 cm-¹. ¹H NMR (400 MHz, D2O, TMSCH2CH2CO2Na as an internal standard): δ = 7.28 (d, J = 7.2 Hz, 2 H, arom.), 7.26 (d, J = 7.2 Hz, 2 H, arom.), 3.96 (s, 8 H, 4 × N+CH 2CO2D), 3.56-3.53 (m, 1 H, N+CHCO2D), 3.43 [t, J = 6.8 Hz, 4 H, N+(CH2CH 2N+)2], 3.26 (t, J = 6.8 Hz, 2 H, CH 2N+D3], 3.19-3.09 [m, 4 H, N+(CH 2CH2N+)2], 2.97 (t, J = 6.8 Hz, 2 H, C6H4CH 2CH2N+D3), 2.67 (t, J = 6.8 Hz, 2 H, CH2CH2CH 2C6H4), 1.87-1.78 (m, 1 H, CH ACH2CH2C6H4), 1.76-1.69 (m, 2 H, CH2CH 2CH2C6H4), 1.64-1.58 (m, 1 H, CH BCH2CH2C6H4). ¹³C NMR (100 MHz, D2O, TMSCH2CH2CO2Na as an internal standard): δ = 177.8 (C, CO2D), 171.8 (4 × C, CO2D), 143.6 (C, arom.), 137.1 (C, arom.), 132.0 (2 × CH, arom.), 131.9 (2 × CH, arom.), 66.2 (CH, N+ CHCO2D), 58.0 (4 × CH2, N+ CH2CO2D), 56.0 [2 × CH2, N+(CH2 CH2N+)2], 49.5 [2 × CH2, N+(CH2CH2N+)2], 43.5 (CH2, CH2N+D3), 37.1 (CH2, one of CH2 CH2 CH2C6H4 CH2), 35.2 (CH2, one of CH2 CH2 CH2C6H4 CH2), 30.5 (CH2, one of CH2 CH2 CH2C6H4 CH2), 30.2 (CH2, one of CH2 CH2 CH2C6H4 CH2). ESI-HRMS: m/z [M - H]- calcd for C25H37N4O10: 553.2510; found: 553.2520. Anal. Calcd for C25H38N4O10˙(HCl)4˙(H2O)4.5: C, 38.42; H, 6.58; N, 7.17. Found: C, 38.32; H, 6.33; N, 7.19.
12

Analytical Data for Compound 10
Colorless oil. FT-IR (neat): 3628, 3448, 3077, 2981, 2366, 2055, 1732, 1642, 1446, 1370, 1343, 1188, 1029, 917, 856, 808, 733 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 5.80 (ddt, J = 16.8, 10.0, 6.8 Hz, 1 H, inside of terminal olefin), 5.08 (d, J = 16.8 Hz, 1 H, an edge of terminal olefin), 5.03 (dt, J = 10.0, 0.4 Hz, 1 H, an edge of terminal olefin), 4.20-4.13 (m, 10 H, 5 × OCH 2CH3), 3.57 (s, 8 H, 4 × NCH 2CO2Et), 3.50 (t, J = 7.6 Hz, 1 H, allyl-CHCO2Et), 2.88-2.77 [m, 6 H, N(CH 2CH AN)2], 2.71-2.66 [m, 2 H, N(CH2CH BN)2], 2.51 (ddd, J = 14.0, 7.6, 6.8 Hz, 1 H, CH ACH=CH2), 2.35 (ddd, J = 14.0, 7.6, 6.8 Hz, 1 H, CH BCH=CH2), 1.285 (t, J = 6.8 Hz, 12 H, 4 × OCH2CH 3), 1.276 (t, J = 6.8 Hz, 3 H, OCH2CH 3). ¹³C NMR (100 MHz, CDCl3): δ = 172.2 (C), 170.9 (4 × C), 134.9 (CH, olefinic), 116.5 (CH2, olefinic), 63.6 (CH, allyl-CHCO2Et), 60.2 (4 × CH2, OCH2CH3), 60.0 (CH2, OCH2CH3), 55.1 (4 × CH2, NCH2CO2Et), 53.3 [2 × CH2, N(CH2 CH2N)2], 50.2 [2 × CH2, N(CH2CH2N)2], 34.3 (CH2, CH2CH=CH2), 14.3 (CH3, OCH2 CH3), 14.1 (4 × CH3, OCH2 CH3). ESI-HRMS: m/z [M + H]+ calcd for C27H48O10N3: 574.3340; found: 574.3331.
Analytical Data for Compound 11
Colorless oil. FT-IR (neat): 3626, 3542, 3453, 3077, 2981, 2938, 2907, 2873, 2386, 2350, 2057, 1883, 1731, 1643, 1465, 1446, 1371, 1344, 1189, 1029, 919, 861, 807, 725, 574 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 5.83 (ddt, J = 16.8, 10.0, 6.8 Hz, 1 H, inside of terminal olefin), 5.08 (d, J = 16.8 Hz, 1 H, an edge of terminal olefin), 5.03 (d, J = 10.0 Hz,
1 H, an edge of terminal olefin), 4.19-4.12 (m, 10 H, 5 × OCH 2CH3), 3.60-3.45 (m, 9 H, 4 × NCH 2CO2Et and allyl-CHCO2Et), 2.90-2.77 [m, 8 H, N(CH 2CH 2N)2], 2.49 (ddd, J = 10.0, 6.8, 6.8 Hz, 1 H, CH ACH=CH2), 2.40 (ddd, J = 10.0, 6.8, 6.8 Hz, 1 H, CH BCH=CH2), 1.29-1.26 (m, 15 H, 5 × OCH2CH 3). ¹³C NMR (100 MHz, CDCl3): δ = 172.3 (C), 171.7 (C), 171.4 (C), 171.1 (2 × C), 134.5 (CH, olefinic), 116.9 (CH2, olefinic), 64.3 (CH, allyl-CHCO2Et), 60.43 (2 × CH2, CH2, OCH2CH3), 60.40 (CH2, OCH2CH3), 60.3 (CH2, OCH2CH3), 60.2 (CH2, OCH2CH3), 55.3 (2 × CH2, NCH2CO2Et), 55.1 (CH2, NCH2CO2Et), 53.2 (CH2, NCH2CO2Et), 52.8 (CH2, NCH2CH2N), 52.7 (CH2, NCH2CH2N), 52.3 (CH2, NCH2 CH2N), 50.7 (CH2, NCH2 CH2N), 34.9 (CH2, CH2CH=CH2), 14.5 (CH3, OCH2 CH3), 14.34 (CH3, OCH2 CH3), 14.31 (2 × CH3, OCH2 CH3), 14.28 (CH3, OCH2 CH3). ESI-HRMS: m/z [M + Na]+ calcd for C27H47O10N3Na: 596.3159; found: 596.3152.

13

During the reaction of 8 (retention time t R = 0.91 min) and 9 in DMF without K2CO3, a newly generated peak (t R = 1.24 min) was observed by UPLC® [BEH C18 1.7 µm column (2.1 mm id. × 50 mm length), linear gradient of MeCN (0.1% TFA) in H2O (0.1% TFA), 40-50% over 5 min, detected by UV at 220 nm]. The new peak was disappeared after the addition of K2CO3, and 10 (t R = 1.65 min) was produced. Accordingly, the new peak may indicate the generation of
N-allylated ammonium intermediate (s). Unfortunately, purification of the intermediate (s) was unsuccessful because of the instability. HPLC separation afforded a mixture of unidentified polar materials along with unreasonably small amounts of 8.

14

Details of Initial Conditions until Optimization
Under the same conditions except for the amount of 9, 10 was obtained in 23% with 3.0 equiv, 36% with 5.0 equiv, 55% with 7.0 equiv, 63% with 9.0 equiv, 62% with 10.0 equiv, 63% with 11.0 equiv, and 61% yield with 12.0 equiv. Thus, the use of 9 equiv of 9 was adequate. When the reaction period of the first process (N-allylation) was shorter than 39 h, not only was the recovery yield of 8 pointlessly increased, but the formation of unignorable amount of isomers 11, di- and tri-allylated compounds was also observed. At this moment, we considered that N-allylation is reversible and the mono-(central-N)-allylated cation to afford 10 is thermodynamically most stable of all the other N-allylated ammonium cations. The final process (C-migration) was terminated when the peak corresponding to the N-allylated cations by UPLC® was disappeared. The reaction at higher temperature than 80 ˚C gave a larger amount of unidentified polar materials. At lower temperature than 80 ˚C, much longer reaction period was required to consume the N-allylated intermediates.

15

When we attempted the same reaction with crotyl bromide, a mixture of inseparable complicated compounds was obtained probably because of the presence of various isomers. Accordingly, the selectivity (α- or γ-selectivity of C-N bond formation for the first step and [2,3]- or [1,2]-sigmatropy for the second step) could not be discussed.