Qiong Hu

Tuned CH Functionalization to Construct Aza‐Podophyllotoxin/Aza‐Conidendrin Derivatives by Means of Domino Cyclization

An efficient domino cyclization method for the construction of aza-podophyllotoxin/aza-conidendrin derivatives has been established. Reactions of different dienes with aryl halides in the presence of a palladium catalytic system produced different kinds of podophyllotoxin derivatives through a highly regioselective C-H functionalization. Treatment of dienes with aryl halides that have electron-withdrawing substituents on the phenyl ring created aza-podophyllotoxin derivatives by means of the functionalization of the C-H bonds ortho to the C-halide bonds of the incoming aryl halides. The reaction of dienes with 1-iodobenzene or aryl halides that incorporate electron-donating groups produced aza-conidendrin derivatives by means of the functionalization of both sp(3) C-H and sp(2) C-H bonds. The regioselective C-H functionalization for the formation of different pseudo-podophyllotoxin/-conidendrin derivatives is proven by analyses of the (1)H NMR spectra of the products and selective X-ray analyses of the structures of the products. Thus, the palladium-catalyzed domino cyclization of 1,6-dienes for the preparation of aza-podophyllotoxin/aza-conidendrin derivatives can be controlled by selectively controlling the C-H functionalization.

Direct Access to Fused Salicylaldehydes and Salicylketones from Tetraynes

A facile method for the synthesis of fused, multifunctionalized salicylaldehydes and salicylketones by a one-pot, three-step cascade hexadehydro-Diels-Alder (HDDA) reaction of tetraynes followed by an intermolecular aldehyde/ketone reaction and hydroxylation is reported. Target compounds were prepared by the condensation of malonates with 3-bromo-1-propyne, and the resulting 2,2-di(1-propyn-3-yl)malonates underwent cross-coupling with phenylethynyl bromides to afford 2,2-di(5-phenyl-2,4-pentadiynyl)malonates, which underwent intramolecular cyclization to produce bicyclic salicylaldehydes. The overall transformation involves the formation of four new C-C bonds and one new Caryl -O bond through both intramolecular and intermolecular reactions. The reaction is easy to perform, proceeds under mild conditions, and exhibits excellent regioselectivity. Water, a simple and readily available reagent, was employed as the OH source. A plausible reaction mechanism is proposed for this new annulation based on isotopic substitution experiments.

Fused Multifunctionalized Chromans from Tetraynes and α,β‐Unsaturated Aldehydes

The synthesis of fused, highly substituted chromenes in a one-pot-three-step cascade hexadehydro-Diels-Alder reaction of tetraynes followed by an intermolecular α,β-unsaturated aldehyde rearrangement is reported. The target compounds were prepared by the condensation of malonates with 3-bromo-1-propyne, and the resulting 2,2-di(1-propyn-3-yl)malonates underwent cross-coupling with phenylethynyl bromides to afford 2,2-di(5-phenyl-2,4-pentadiynyl)malonates, which underwent intramolecular cyclization to produce tricyclic chromenes. The overall transformation involves the formation of four new C-C bonds and one new C-aryl-O-C-aryl bond by both intramolecular cyclization and intermolecular rearrangement reactions. These constitute a key strategy for the construction of a highly substituted natural chromene core and a robust method for producing other chromenes.

Fused multifunctionalized isoindole-1,3-diones via the coupled oxidation of imidazoles and tetraynes

The facile synthesis of fused multifunctionalized isoindole-1,3-diones by a hexadehydro-Diels–Alder domino reaction of various substituted tetraynes and imidazole derivatives is reported. The overall transformation involved the formation of three new C–C bonds and two new Caryl–O bonds via intramolecular cyclization and intermolecular coupling oxidation reactions.