Abstract
The synthetic scope of asymmetric 5′,6-disubstituted-2,2′-bipyridines in the preparation of flexible multitopic ligands has been investigated. The preparation of the pivotal 6-bromo-5′-bromomethyl-2,2′-bipyridine building block involved a Kröhnke protocol followed by a radical bromination reaction which has been optimized. Functionalization of 6-bromo-5′-bromomethyl-2,2′-bipyridine has been realized by both a Delepine and a Gabriel reaction, providing after hydrolysis the corresponding amino compound, whereas a nucleophilic attack of acetate followed by a saponification reaction provided the corresponding alcohol. Multifunctionalized bipyridine ligands have been prepared in one step from 6-bromo-5′-bromomethyl-2,2′-bipyridine and acyclic amines or primary alcohol via base-assisted nucleophilic substitutions. In all cases, transformation of the bromo-function to the corresponding ethyl esters has been made possible under mild conditions using a palladium promoted carboethoxylation reaction, while saponification under basic conditions provided the corresponding acids after protonation. The utility of the herein reported protocols has been extended to the synthesis of an ethylenediamine platform bearing an appended 4-nitrobenzyl group for potential linking to other molecules.
Key words
bromination - pyridines - bipyridines - ligands - radical reaction - nucleophilic additions
References
1 Ziessel R. In
Photosensitization and Photocatalysis Using Inorganic and Organometallic Compounds
Kalyanasundaram K.
Grätzel M.
Kluver;
Dordrecht:
1993.
p.217-240
2 Deronzier A.
Moutet J.-C.
Coord. Chem. Rev.
1996,
147:
339
3 Montalti M.
Prodi L.
Zaccheroni N.
Charbonnière LJ.
Douce L.
Ziessel R.
J. Am. Chem. Soc.
2001,
123:
12694
4 Gao FG.
Bard AJ.
J. Am. Chem. Soc.
2000,
122:
7426
5 Wang J.
Wang R.
Yang J.
Zheng Z.
Carducci MD.
Cayou T.
Peyghambarian N.
Jabbour GE.
J. Am. Chem. Soc.
2001,
123:
6179
6a Blackburn GF.
Shah HP.
Kenten JH.
Leland J.
Kamin RA.
Link J.
Clin. Chem.
1991,
37:
1534
6b Ege D.
Becker WG.
Bard AJ.
Anal. Chem.
1984,
56:
2413
7a Evangelista RA.
Pollak A.
Allore B.
Templeton EF.
Morton RC.
Diamandis EP.
Clin. Biochem.
1988,
21:
173
7b Saha AK.
Kross K.
Kloszewski ED.
Upson DA.
Toner JL.
Snow RA.
Black CDV.
Desai VC.
J. Am. Chem. Soc.
1993,
115:
11032
7c Hemmilä I.
Harju R. In
Biological Applications of Labelling Technologie
Emmilä I.
Stahlberg T.
Mottram P.
Wallac Oy and EG&G;
Cie:
1995.
7d Vereb G.
Jares-Erijman E.
Selvin PR.
Jovin TM.
Biophys. J.
1998,
74:
2210
7e Bornhop DJ.
Hubbard DS.
Houlne MP.
Adair C.
Kiefer GE.
Pence BC.
Morgan DL.
Anal. Chem.
1999,
71:
2607
7f Griffin JMM.
Skwierawska AM.
Manning HC.
Marx JN.
Bornhop DJ.
Tetrahedron Lett.
2001,
42:
3823
8 Wieder I. In
Immunofluorescence and Related Staining Techniques. Proceedings of the VIth International Conference on Immunofluorescence and Related Staining Techniques
Knapp W.
Holubar K.
Wick G.
Elsevier, North-Holland Biomedical Press;
Amsterdam:
1978.
p.67
9 Soini E.
Kojola H.
Clin. Chem.
1983,
29:
65
10 Charbonnière LJ.
Guardigli M.
Cesario M.
Roda A.
Sabbatini N.
Ziessel R.
J. Am. Chem. Soc.
2001,
123:
2436
11 Charbonnière LJ.
Weibel N.
Ziessel RF.
Tetrahedron Lett.
2001,
42:
659
12 Ulrich G.
Bedel S.
Picard C.
Tisnès P.
Tetrahedron Lett.
2001,
42:
6113
13a Mukkala V.-M.
Kwiatkowski M.
Kankare J.
Takalo H.
Helv. Chim. Acta
1993,
76:
893
13b Takalo H.
Hemmilä I.
Sutela T.
Latva M.
Helv. Chim. Acta
1996,
79:
789
14 Piguet C.
Bünzli J.-CG.
Chem. Soc. Rev.
1999,
28:
347
15 Charbonnière, L. J.; Weibel, N.; Ziessel, R. F. ; J. Org. Chem ., 2001 , in press.
16 Parks JE.
Wagner BE.
Holm RH.
J. Organometal. Chem.
1973,
56:
53
17 King LC.
J. Am. Chem. Soc.
1944,
66:
894
18 Kröhnke F.
Synthesis
1976,
1
19 El Ghayoury A.
Ziessel R.
J. Org. Chem.
2000,
65:
7757
20a Savage SA.
Smith AP.
Fraser CL.
J. Org. Chem.
1998,
63:
10048
20b Fraser CL.
Anastasi NR.
Lamba JJS.
J. Org. Chem.
1997,
62:
9314
20c Lamba JJS.
Fraser CL.
J. Am. Chem. Soc.
1997,
119:
1801
21 Ziessel R.
Hissler M.
Ulrich G.
Synthesis
1998,
1339
22 Weibel, N.; Charbonnière, L. J.; Ziessel, R.F., unpublished results.
23 El-ghayoury A.
Ziessel R.
Tetrahedron Lett.
1998,
39:
4473 , and references cited therein.
24a Schoenberg A.
Bartoletti I.
Heck RF.
J. Org. Chem.
1974,
39:
3318
24b Schoenberg A.
Heck RF.
J. Org. Chem.
1974,
39:
3327
25 De Almeida MV.
Cesar ET.
Felicio EDCA.
Fontes APS.
Robert-Gero M.
J. Braz. Chem. Soc.
2000,
11:
154
26 Hanan GS.
Schubert US.
Volkmer D.
Rivière E.
Lehn J.-M.
Kyritsakas N.
Fischer J.
Can. J. Chem.
1997,
75:
169
