In 7-azaindole

The electron density on the pyrrole nitrogen atom in 7-azaindole is a little lower than in indole however, N(d acylation of the azaindoles proceeds readily under mild conditions. 

Scheme 1 Excited state double-proton transfer (ESDPT) in 7-azaindole (7-AI) dimers.

Scheme 2a Solvent-mediated proton transfer in 7-azaindole.

Figure 29.18 Calculated structures of the stationary points along the reaction coordinate for the excited state tautomerization in 7-azaindole complexes with one, two and five water molecules [17].

Chon P-T, Martinez M L, Cooper W C, et al. (1992) Monohydrate catalysis of excited-state donble-proton transfer in 7-azaindole. J. Phys. Chem. 96 5203-5205. 

Such a principle was effectively employed in the synthesis of both achiral and chiral heterocyclic compounds. For instance, O Shea et al. [8] have demonstrated the benefit of intermolecular carbolithiations of o-substituted styrenes 9a in a one-pot synthesis of substituted indoles 11a and have extended this principle to the carbolithiation of 3-vinylpyridin-2-ylamines 9b eventually resulting in 7-azaindoles 11b (Scheme 10.5). 

One of the most important issues for multi-proton transfer reactions is their mechanism do they occur stepwise or concertedly Schowen highlighted this issue with four examples mutarotation of glucose with 2-pyridone tauto-merization of porphyrin molecules " alcohol-mediated double proton transfer in 7-azaindole and isomerization in 7-azaindole dimer. However, in the 7-azaindole dimer, the mechanism of the excited-state double proton transfer has not been fully resolved, even though careful experimental and quantum mechanical studies have been performed. " The excited-state reaction... 

Catalan, )., del Valle, J., and Kasha, M. (1999) Resolution of concerted versus sequential mechanisms in photo-induced double-proton transfer reaction in 7-azaindole H-bonded dimer. Proc. Natl. Acad. Sci. U.S.A., 96, 8338-8343. 

Figure 3.19 Resolution of the concerted versus stepwise mechanism of excited-state double proton transfer in doubly hydrogen-bonded dimer of 7-azaindole [90, 91]. Schematic presentations of (a) the concerted, one-step, synchronous double proton transfer in 7-azaindole dimer and (b) the stepwise proton transfer following formation...

Hetherington, W. M., Ill, Micheels, R. H., and Eisenthal, K. B., Picosecond dynamics of double proton transfer in 7-azaindole dimers, Chem. Phys. Lett., 66, 230,1979. 

At its best, the study of solvent kies by the formalism given can be used to learn about proton content and activation in the transition state. For this reason it is known as the proton inventory technique. The kinetics of decay of the lowest-energy electronic excited state of 7-azaindole illustrates the technique.25 Laser flash photolysis techniques (Section 11.6) were used to evaluate the rate constant for this very fast reaction. From the results it was suggested that, in alcohol, a double-proton tautomerism was mediated by a single molecule of solvent such that only two protons are involved in the transition state. In water, on the other hand, the excited state tautomerism is frustrated such that two water molecules may play separate roles. Diagrams for possible transition states that can be suggested from the data are shown, where of course any of the H s might be D s. 

Rate constants" for the excited state decay of 7-azaindole in H/D solvent mixtures... 

Additional combinatorial variation sites allow the heterocyclic self-assembly units. Thus, it has been shown that heterocycles 11 and 14-17 can serve as A-analogous donor-acceptor ligands self-assembling with the T-analogous acceptor-donor ligands isoquinolone 12 and 7-azaindole 18 (Scheme 30) [92]. All combinations form the heterobidentate ligands exclusively upon simple mixing in the presence of a transition metal salt (proven by X-ray, NMR). 

Blue luminescence of zinc complexes of pyridyl-containing complexes is an area of current interest.277 Design of blue luminescent materials is of relevance to display applications, as blue-light-emitting diodes, and to this end Che examined solution luminescence of zinc pyridylamine complexes.73,278 Che and co-workers studied the complex Zn40(7-azaindoyl)6 which has a blue emission at 433 nm in the solid state.279,280 In an attempt to improve on stability Wang et al. examined compounds with neutral 7-azaindole and an A-functionalized pyridyl derivative.281 In contrast with other metal complexes of the neutral 7-azaindole (32), Zn(7-azaindole)2(OAc)2 is a blue luminescent compound and a A-(2-pyridyl) 2-azaindole (33) and its complexes were also... 

A tetrameric structure with the Zn40 core can also be formed with the 7-azaindolate ligand, [Zn40(C7H5N2)6], and has been structurally characterized. The tetramer displays intense photoluminescence at 448 nm in the solid state and 425 nm in acetonitrile with a lifetime and quantum yield of 0.1 ps and 0.17 ps respectively.280... 

Cossy and coworkers described a precise combination of a Heck and a Suzuki-Miyama reaction using ynamides and boronic acids to give indole and 7-azaindole derivatives [46]. Thus, reaction of 6/1-73 with 6/1-74 using Pd(OAc)2 as catalyst led to 6/1-75 in 68% yield (Scheme 6/1.18). 

Chou PT, Yu WS, Wei CY et al (2001) Water-catalyzed excited-state double proton transfer in 3-cyano-7-azaindole the resolution of the proton-transfer mechanism for 7-azaindoles in pure water. J Am Chem Soc 123 3599-3600... 

Hsieh CC, Chen KY, Hsieh WT et al (2008) Cyano analogues of 7-azaindole probing excited-state charge-coupled proton transfer reactions in protic solvents. ChemPhyChem 9 2221-2229... 

Mentus S, Maroncelli M (1998) Solvation and the excited-state tautomerization of 7-azaindole and 1-azacarbazole computer simulations in water and alcohol solvents. J Phys Chem A 102 3860-3876... 

The medicinal importance of 2-aryltryptamines led Chu and co-workers to develop an efficient route to these compounds (130) via a Pd-catalyzed cross-coupling of protected 2-bromotryptamines 128 with arylboronic acids 129 [137]. Several Suzuki conditions were explored and only a partial listing of the arylboronic acids is shown here. In addition, boronic acids derived from naphthalene, isoquinoline, and indole were successfully coupled with 128. The C-2 bromination of the protected tryptamines was conveniently performed using pyridinium hydrobromide perbromide (70-100%). 2-Phenyl-5-(and 7-)azaindoles have been prepared via a Suzuki coupling of the corresponding 2-iodoazaindoles [19]. 

Other indoles that have been prepared using the Sonogashira coupling and cyclization sequence include 5,7-difluoroindole and 5,6,7-trifluoroindole [219], 4-, 5-, and 7-methoxyindoles and 5-, 6-, and 7-(triisopropylsilyl)oxyindoles [220], the 5,6-dichloroindole SB 242784, a compound in development for the treatment of osteoporosis [221], 5-azaindoles [222], 7-azaindoles [160], 2,2-biindolyls [223,176], 2-octylindole for use in a synthesis of carazostatin [224], chiral indole precursors for syntheses of carbazoquinocins A and D [225], a series of 5,7-disubstituted indoles [226], a pyrrolo[2,3-eJindole [226], an indolo[7,6-g]indole [227], pyrrolo[3,2,l-y]quinolines from 4-arylamino-8-iodoquinolines [228], optically active indol-2-ylarylcarbinols [229], 2-alkynylindoles [176], 7-substituted indoles via the lithiation of the intermediate 2-alkynylaniline derivative [230], and a variety of 2,5,6-trisubstituted indoles [231], This latter study employs tetrabutylammonium fluoride, instead of Cul or alkoxide, to effect the final cyclization of 215 to indoles 216 as summarized here. 

Somei adapted this chemistry to syntheses of (+)-norchanoclavine-I, ( )-chanoclavine-I, ( )-isochanoclavine-I, ( )-agroclavine, and related indoles [243-245, 248]. Extension of this Heck reaction to 7-iodoindoline and 2-methyl-3-buten-2-ol led to a synthesis of the alkaloid annonidine A [247]. In contrast to the uneventful Heck chemistry of allylic alcohols with 4-haloindoles, reaction of thallated indole 186 with 2-methyl-4-trimethylsilyl-3-butyn-2-ol affords an unusual l-oxa-2-sila-3-cyclopentene indole product [249]. Hegedus was also an early pioneer in exploring Heck reactions of haloindoles [250-252], Thus, reaction of 4-bromo-l-(4-toluenesulfonyl)indole (11) under Heck conditions affords 4-substituted indoles 222 [250], Murakami described the same reaction with ethyl acrylate [83], and 2-iodo-5-(and 7-) azaindoles undergo a Heck reaction with methyl acrylate [19]. 

The 5-, 6-, and 7-azaindoles were synthesized via the Pd-catalyzed heteroannulation of internal alkynes using orf/w-aminopyridine derivatives in an extention of Larock s indole synthesis [169], LiCl was found to be an essential component in order to obtain regioselectivity, reproducibility and improved yields. 

N-Formyl-7-azaindole (81) is predominantly (750MR(6)445) in the E form, which minimizes electrostatic interactions between O and N. 

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