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Benzene ring functionalization provides useful alternatives to access indole derivatives and has received much attention in recent years. In this work, the mechanism of Pt(II)-catalyzed cyclization/alkynylation of benziodoxole with pyrrole homopropargylic ethers to generate C5-alkenylated indole derivatives has been studied with the aid of density functional theory (DFT) calculations. We found that five-membered-ring cyclization/six-membered-ring cyclization is competitive in the formation of an indole skeleton. The following aromatization stage prefers the reaction sequence bicarbonate-assisted deprotonation at the C3a position, H2CO3-promoted methoxy elimination at the C7 position, and bicarbonate-assisted deprotonation at the C6 position. In the last alkynylation stage, the oxidative substitution mechanism assisted by H2CO3 is found to be favored over the previously proposed 1,2-iodo shift and oxidative addition. The overall rate-determining step is oxidative substitution. Additionally, an interesting substituent effect on chemoselectivity was investigated. The electronic and steric effects caused by methyl result in reverse chemoselectivity. [ABSTRACT FROM AUTHOR]

Cu-catalyzed cyanation of indoles with acetonitrile for the synthesis of 3-cyanoindoles has been developed. The Cu/TEMPO/(Me3Si)2 system has been identified to promote highly efficient and selective C-H cyanation of indoles by use of unactivated acetonitrile as a cyano source via a sequential iodination/cyanation process in one pot. This reaction furnishes 3-cyanoindoles in moderate to good yields and tolerates a series of functional groups. Moreover, low-cost copper catalysts and hazardless acetonitrile as a cyano source feature the practicability of this reaction. [ABSTRACT FROM AUTHOR]

A procedure that converts a series of structurally diverse, readily available indole derivatives to their corresponding indolequinones is described. The three-step route commences with an iridium catalyzed C--H borylation to give a 7-borylindole that upon oxidation-hydrolysis affords the 7-hydroxyindole. Subsequent oxidation provides the indolequinone. [ABSTRACT FROM AUTHOR]

By means of Sonogashira reaction, a series of 2-alkynyl- and 2,7-dialkynyl derivatives of 1,8-bis(dimethylamino)naphthalene ("proton sponge") have been obtained from the corresponding iodides. It was disclosed that changing the reaction conditions and isolation protocol or conducting the model experiments with the authentic acetylenes results in several types of palladium- and copper-assisted heterocyclizations with the participation of the C≡C bond and 1-NMe2 group. These include: (i) a cyclization into isomeric 1H-benzo[g]indoles with [1,3] migration of the N-methyl group into the newly formed pyrrole ring; (ii) a similar cyclization with a loss of the methyl group; (iii) a tandem process of cyclization into benzo[g]indoles and their subsequent 3,3'-dimerization; and (iv) a copper-catalyzed oxidative transformation into 3-aroylbenzo[g]indoles. In most cases, the reactions occur in parallel, but under certain conditions, one of the above products becomes predominant or even the only one. Remarkably, in Pd-catalyzed cyclizations i-iii, the acetylenic bond behaves as an electrophile being attacked at the β-position by the amine nitrogen atom. In contrast, in transformation iv, the C≡C bond attacks by its Cα atom on the aminomethyl radical functionality N(Me)-CH2 presumably arising at copper oxidation/deprotonation of the 1-NMe2 group. Studying rearrangement i, some evidence for the porcelain catalysis was obtained. [ABSTRACT FROM AUTHOR]

An efficient formal synthesis of (±)-cycloclavine is achieved in seven steps and 27% overall yield from the known 2-(4-bromo-1-tosyl-1H-indol-3-yl)acetaldehyde. Key features include an iron(III)-catalyzed aza-Cope--Mannich cyclization and an intramolecular Heck reaction or a self-terminating 6-exo-trig aryl radical--alkene cyclization. [ABSTRACT FROM AUTHOR]

Environment polarity can cause changesin absorbance or emissionmaxima, for a given fluorophore. This is termed solvatochromism. Inthis study semiempirical models of solvatochromic shifts are usedto predict their lipid bilayer location. Four reaction field modelsare analyzed and compared, to provide the most accurate predictionof fluorophore solvatochromic shifts using a modified version of theLippert equation. For curcumin, the reaction field of Block and Walkergave the strongest agreement between experimental and predicted values(r= 0.978, p< 0.0001). Foraluminum phthalocyanine disulfonic acid (AlPcS2), the reactionfield of Wertheim, based on statistical mechanics, gave the best agreement(r= 0.951, p= 0.001) only whendispersion forces and solute polarizability are considered. The resultsof these models are correlated to the Dimroth–Reichardt ET(30) solvent polarity scale used by Frimer and colleagues.Using the model predicted values, curcumin is estimated to be 1–1.2nm from the phospholipid–water interface, in the acyl chainregion of the lipid bilayer. AlPcS2is predicted to be0.7–0.9 nm from the interface, at the fatty acid carbonyl.This investigation provides semiempirical methods to efficiently linkfluorophore solvatochromic shifts to a location in the lipid bilayervia reaction field models. [ABSTRACT FROM AUTHOR]