Diastereoselective Synthesis of Dibenzoazepines through Chelation on Palladium(IV) Intermediates

Joint palladium/norbornene organometallic catalysis allows for straightforward access to dibenzo­[<i>c,e</i>]­azepines. These synthetically challenging polycyclic frameworks form in one pot via a three-component coupling of an aryl iodide, a bromobenzylamine, and an olefin. A key, atroposelective aryl–aryl coupling from chelated Pd­(IV) intermediates dictates the outcome of the cascade. DFT modeling sheds light on the complex mechanism that allows the complete diasteroselectivity to be observed

Diastereoselective Synthesis of Dibenzoazepines through Chelation on Palladium(IV) Intermediates

Joint palladium/norbornene organometallic catalysis allows for straightforward access to dibenzo­[<i>c,e</i>]­azepines. These synthetically challenging polycyclic frameworks form in one pot via a three-component coupling of an aryl iodide, a bromobenzylamine, and an olefin. A key, atroposelective aryl–aryl coupling from chelated Pd­(IV) intermediates dictates the outcome of the cascade. DFT modeling sheds light on the complex mechanism that allows the complete diasteroselectivity to be observed

Acid-Catalyzed Formal Cycloaddition of α,β-Unsaturated Carbonyls with Epoxides: Dioxepines or Acetals?

It has been recently reported that the reaction of α,β-unsaturated carbonyl derivatives with epoxides in the presence of a homogeneous acid catalyst readily delivers the corresponding dioxepines via formal (4 + 3) cycloaddition. We report herein that the same apparent reactivity can be triggered via heterogeneous catalysis. Characterization of products by means of NMR correlation experiments and DFT modeling revealed, however, that products are the acetals of the unsaturated reagent rather than the desired heterocycles

Pd-Catalyzed/Iodide-Promoted α‑Arylation of Ketones for the Regioselective Synthesis of Isocoumarins

A variety of isocoumarins have been synthesized directly from 2-halobenzoates and ketones through a palladium-catalyzed α-arylation step followed by an intramolecular cyclization process. The addition of iodide anions to the reaction mixture increased yields and selectivities especially when 2-bromobenzoates were employed. This phosphine-free one-pot synthesis features a high functional group tolerance and gives access to richly decorated isocoumarins. This general methodology was successful in the total synthesis of Xyridin A, an important natural product with antibacterial and antifungal activity

Rearrangements of <i>N</i>‑Acyl Isothioureas. Alternate Access to Acylguanidines from Cyanamides

We report a tin-free one-pot radical approach to the synthesis of <i>N</i>-acyl isothioureas and acylguanidines from <i>N</i>-acyl cyanamides. Photoactivated reduction of aromatic disulfides in the presence of Hünig’s base results in hydrothiolation of the cyanamide moiety, followed by spontaneous 1,3-migration of the acyl group. Onward reaction of the isothioureas obtained with amines led to the corresponding <i>N</i>-acylguanidines, where the acyl group is attached to the nitrogen atom formerly at the cyano-end of the starting material

Alternative Routes to Tricyclic Cyclohexenes with Trinuclear Palladium Complexes

Highly symmetric all-metal aromatic Pd₃⁺ complexes can catalyze the cycloisomerization of terminal 1,6-enynes and internal dienynes under mild conditions. Modification of substrates dictates the mechanism and steers the reaction toward different polycyclic frameworks, enabling the development of complex cascades. The reactivity of Pd­(⁴/₃) complexes is complementary to that of mononuclear Pd(0) and Pd­(II) ones

Pd Catalysis in Cyanide-Free Synthesis of Nitriles from Haloarenes via Isoxazolines

A method to obtain aryl nitriles from the corresponding halides by Pd catalysis, in the absence of any cyanide source, is reported. The reaction of an aryl halide, ethyl nitroacetate, and an olefin readily delivers an aromatic nitrile. A variety of aryl iodides/bromides have been converted into the corresponding cyanoarenes in fair to excellent yields. The reaction likely involves the following steps: (a) Pd-catalyzed α-arylation of ethyl nitroacetate; (b) nitrile oxide formation; (c) [3 + 2]-cycloaddition with an olefin to provide an isoxazoline; (d) isoxazoline cleavage to benzonitrile formation

Synthesis of Carbolines via Palladium/Carboxylic Acid Joint Catalysis

The combination of a Pd(0) complex with benzoic acid converts propargylic tryptamines to the corresponding tetrahydro-β-carbolines. The method uses unprotected indoles and affords the desired products with ample functional group tolerance. Detailed modeling studies reveal a close synergy between the organic and metal catalysts, which enables sequential alkyne isomerization, indole C–H activation, and eventual C–C reductive elimination to afford the target heterocycles