A NEW CLASS OF PYRAZOLOPYRIDINE NUCLEUS OBTAINED THROUGH EITHER RADICAL OR Pd ARYLATION PATHWAY FROM N-AZINYLPYRIDINIUM N-AMINIDES Abet, Valentina; Nuñez, Araceli; Mendicuti, Francisco; Burgos, Carolina and Alvarez-Builla, Julio Departamento de Química Orgánica and Departamento de Química Fisíca, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain References 1. Nuñez, A.; Sanchez, A.; Burgos, C.; Alvarez-Builla, J. Tetrahedron 2007, 63, Núñez, A.; Garcia de Viedma, A.; Martinez-Barrasa, V.; Burgos, C.; Alvarez-Builla, J. Synlett 2002, Hernandez, S.; SanMartin, R.; Tellitu, I.; Domınguez, E. Org. Lett. 2003, 5, Campeau, L. C.; Rousseaux, S.; Fagnou, K. J. Am. Chem. Soc. 2005, 127, Introduction In the course of our studies on the reactivity of pyridinium N-aminides 1 (i.e 1, Scheme 1), it has been shown that it is possible to generate the pyrazolopyridine nucleus 2 and 3 from this kind of compounds, using both a radical or a Pd-direct arylation pathway. Moreover, we will report a preliminary study of their fluorescent properties. EntryYR Tricyclic Product Yield (%) Method A a Yield (%) Method B,C Yield (%) Method D d 1CH-2a5672 B 81 2CHH3a29 73 B 59 3CH4-Me3b3240 B 63 4CH4-MeO3c3037 B 70 5CH4-MeCO 3d953 B 51 6N-2b NH3e3478 C 59 8N4-Me3f3541 C 74 9N4-MeO3g4539 C 74 10N4-MeCO3h3231 C 66 a TTMSS (2 equiv), AIBN (2 equiv) in MeCN/PhH are added during 32 h, K 2 CO 3 (2 equiv) and the N-aminide (1 equiv) in MeCN, 80 ºC, 24 h. b N-amidine (1 equiv), Pd(OAc) 2 (20% mol), K 2 CO 3 (5 equiv), LiCl (1.5 equiv), n-Bu 4 NBr (1 equiv) in DMF, MW (170ºC, 10 min). c N-amidine (1 equiv), Pd(OAc) 2 (20% mol), K 2 CO 3 (5 equiv), LiCl (1.5 equiv), n-Bu 4 NBr (1 equiv) in DMF, MW (150ºC, 80 min). d N- Pyridinium salt 6 (1 equiv), Pd(OAc) 2 (20% mol), K 2 CO 3 (5 equiv), LiCl (1.5 equiv), n- Bu 4 NBr (1 equiv) in DMF, MW (170ºC, 10 min). Acknowledgments The authors acknowledge support for this work from the MCYT through project CTQ /BQU and grants from the MEC (A.V. and A.V). Conclusions This study represents the first example of an intramolecular addition of an aryl radical to a -deficient pyridinium fragment linked to a - excessive 2-azinyliminopyridine moiety to furnish dipyridopyrazole and pyridopyrazolopyrazine derivatives 3. In all the cases, Pd-direct arylation, using microwave irradiation, furnishes better results. Our approach permits the preparation of the fully aromatic nucleus, which exhibit a high degree of conjugation and consequently possess multiple pathways for intramolecular electronic and photonic transfer and display a bright-yellow strongly fluorescent properties. Results The slow dropwise addition (32 h, syringe pump) of a solution of azobisisobutyronitrile and tris(trimethylsilyl)silane as initiator and mediator of the radical process 2 to a solution of the corresponding N-aminide, furnishes only poor yields of tricyclic derivatives 2 or 3. Better results are obtained through a Pd-direct arylation metodology, from N-aminides 4 or 5, or from N-pyridinium sals 6, having in mind the work reported by Dominguez and col. 3 concerning to Heck-like process and the Fagnou’s experiments, 4 and using microwave irradiation, as shown in the Table 1. 3a 2a 3c 3d 3b Fluorescence studies Figure 1 depicts the emission spectra of derivates 2 and 3 obtained in THF at 25ºC, upon excitation to the low energy band of the absorption spectra. The presence of an aryl containing -electron moiety on the dipyridopyrazole nucleus contributes to extending the -delocalization by stabilizing the system, and thus inducing a shift on the *- transitions to a higher wavelength. Table 2 collects the fluorescence quantum yields ( f ) and lifetimes (τ) for all the systems studied in THF at 25 ºC upon excitation at the selected wavelengths. 3g 2b 3h 3f 3e SampleYZλ exc (nm)λ em (nm) fafa τ (10- 9 s) 2aCHCl aCHC6H5C6H bCH4-MeC 6 H cCH4-MeOC 6 H dCH4-MeCOC 6 H bNCl eNC6H5C6H fN4-MeC 6 H gN4-MeOC 6 H hN4-MeCOC 6 H Table 2 Figure 1 a Fluorescence quantum yields ( f ) were performed using quinine sulphate in 0.1 M sulfuric acid as standard.