Differential Reactivities of Enyne Substrates in Ruthenium- and Palladium-Catalyzed Cycloisomerizations

Abstract

Complementary methods for the transition metal-catalyzed enyne cycloisomerizations of cyclic olefins have been developed. By using distinct ruthenium and palladium catalysts, decalins and 7,6-bicycles can be obtained with dichotomous stereochemical outcomes. The change in mechanism that accompanies the change in metal affords trans-fused 1,4-dienes with ruthenium and their cis-fused diastereomers under palladium catalysis. In the reactions under ruthenium catalysis, a coordinating group is required, and acts to direct the metal to the same side of the carbocycle, resulting in the observed trans diastereoselectivity. Subtle changes in the carbocyclic substrate led to the discovery of a heretofore-unobserved mechanistic pathway, providing bicyclic cycloisomerization products under palladium catalysis and tricyclic products under ruthenium catalysis in DMA. The differential effect of DMA supports a mechanism in which the coordination requirements of the two paths differ, allowing for the reaction to be shuttled through the metallacycle pathway (generating tricyclic products) when DMA is used as a solvent.

Cyclobutene Formation in PtCl2‐Catalyzed Cycloisomerizations of Heteroatom‐Tethered 1,6‐Enynes

“…However, although this condition is necessary, it is not sufficient: DMA as the coordinating solvent plays a decisive role in the evolution of the ionic species to the cyclobutene. Nevertheless, the exact role of amide ligands in favoring the formation of cyclobutenes remains to be established 13…”

The Palladium-Catalysed Intramolecular Alder-ene (IMAE) Reactions of Certain Heteroatom-Linked 1,6-Enynes: The Formation of Hexahydro-Indoles and -Benzofurans

“…[14b] Stereochemically divergent outcomes have been observed in the ruthenium-and palladium-catalysed cycloisomerisations of cyclohexene-derived 1,7-enynes leading to decalin-containing products. [15] Extensions of such Ru-catalysed processes to the synthesis of certain alkaloid frameworks have been reported recently. [16] Reductive cycloisomerisations of 1,6-enynes catalysed by either palladium or rhodium have been reported by Trost and Rise [17] and Jang and Kirsche, [18] respectively.…”

“…While we rapidly established a method for preparing an enyne, 27, that seemed suitable for participation in the desired cycloisomerisation reaction, this process was overwhelmed by a 15 16 Palladium-Catalysed IMAE Reactions C competing coupling of the terminal alkyne residues of two separate substrate molecules to afford a 1,3-enyne-containing heterodimer (Chart 3).…”

Palladium‐Catalyzed Cycloisomerization of 1,6‐Enynes Using Alkyl Iodides as Hydride Source: a Combined Experimental and Computational Study

“…[1] Among these transformations, 1,n-enynes have been particularly explored as cycloisomerization substrates, thus affording a wide range of products depending on the choice of different palladium catalysts and coupling partners. [2] The system of palladium catalysts and acetic acid was often used in the cycloisomerization of 1,n-enynes, in which a palladium hydride was generated through oxidative addition of acetic acid to the Pd(0) center, and subsequent selective addition of palladium hydride was involved as the key step in these transformation. [1c,3] Unfortunately, these conditions preclude the use of partners sensitive to acidic media.…”