Brønsted/Lewis Acid-Promoted Site-Selective Intramolecular Cycloisomerizations of Aryl-Fused 1,6-Diyn-3-ones for Diversity-Oriented Synthesis of Benzo-Fused Fluorenes and Fluorenones and Naphthyl Ketones.

Herein, a facile diversity-oriented approach to access functionalized benzo[a]fluorenes, benzo[b]fluorenones, and naphthyl ketones has been demonstrated via site-selective intramolecular cyclization of aryl-fused 1,6-diyn-3-ones. Synthesis of benzo[a]fluorenes and naphthyl ketones has been achieved selectively using TfOH and AgBF4, respectively, via in situ-formed acetals. Aryl-fused 1,6-diyn-3-ones undergo triflic acid-mediated intramolecular cyclization, leading to benzo[b]fluorenone derivatives via a radical intermediate as supported by EPR studies. Kinetic studies of these transformations have also been performed by UV-visible spectroscopic analysis to shed light on the reaction profile.

Annulation of a Highly Functionalized Diazo Building Block with Indoles under Sc(OTf)3/Rh2(OAc)4 Multicatalysis through Michael Addition/Cyclization Sequence.

A highly functionalized and easily accessible six-carbon diazo building block has been developed and utilized as a 1,4-diacceptor for an efficient synthesis of functionalized tetrahydrocarbazoles, carbazoles, and tetrahydropyrido[1,2- a]indoles. The synthesis involves concurrent tandem catalysis by Sc(OTf)3 and Rh2(OAc)4. The role of Sc(OTf)3 is critical as it facilitates both the initial intermolecular Michael reaction of the indole and the subsequent Rh(II)-catalyzed intramolecular annulation. The products, tetrahydrocarbazoles and tetrahydropyridoindoles, are equipped with a ß-ketoester and ester functionalities which can be utilized for further synthetic elaborations.

The directing group wins over acidity: kinetically controlled regioselective lithiation for functionalization of 2-(2,4-dihalophenyl)-1,3-dithiane derivatives.

Regioselective lithiation followed by functionalization of 2-(2,4-dihalophenyl)-1,3-dithiane derivatives with different electrophiles was achieved in good to excellent yields. When the title compound is treated with n-butyl lithium, lithiation occurs selectively at the aromatic carbon having less acidic proton despite the presence of thermodynamically more acidic 1,3-dithiane proton in the same molecule. Computationally calculated pKa values of the available reactive site protons and the experimental results suggest that the regioselective lithiation in 2-(2,4-dihalophenyl)-1,3-dithiane derivatives is not governed by thermodynamic acidity rather exclusively dictated by the kinetic removal of protons due to cooperative coordination (complex induced proximity effect, CIPE) and inductive effects of the 1,3-dihalo substituents present in the aromatic ring. By employing this regioselective functionalization, diverse 1,2,3,4-tetra-substituted aromatic compounds were prepared with ease.