The Gilded Edge in Acetylenic Scaffolding II: A Computational Study of the Transmetalation Processes Involved in Palladium-Catalyzed Cross-Couplings of Gold(I) Acetylides

Abstract

The palladium-catalyzed cross-coupling reaction between phosphine-gold­(I) acetylides and aryl iodides has recently proven as a convenient alternative to the standard Sonogashira reaction, which instead employs terminal alkynes as substrates. This alternative reaction does not require the presence of an amine base, but still, however, requires a copper cocatalyst (CuI). In this theoretical work we have investigated the possible roles that this copper catalyst may play. Three transmetalation pathways can be imagined, proceeding by either (i) transferring the acetylide from gold to copper and thereafter to palladium, (ii) directly transferring the acetylide from gold to palladium, or (iii) directly transferring the acetylide from gold to palladium but aided by a copper coordination to the triple bond. Calculations reveal that the first of these is the most viable reaction pathway, as it involves the initial formation of a very favorable copper/gold acetylide complex. The transmetalations along this pathway run via several equilibria.

Sonogashira-Like Coupling Reactions with Phosphine–Gold(I) Alkynyl Complexes

“…Penta-1,3-diyn-3-one presents an example of one such unstable compound, which is difficult to handle. 15 A protodesilylation of its trimethylsilyl-protected precursor 18 (shown in Scheme 8) followed by treatment with iodobenzene (19) under Sonogashira conditions has been carried out in the author's laboratory, but none of the desired Sonogashira coupling product was obtained. 16 However, converting 18 into the gold species 20 (isolated in high yield) 16,17 and employing this compound as a substrate in the Sonogashira coupling with 19 gave the desired product 21 (Scheme 8).…”

“…As Cu(I) is required in order to run the coupling reaction at room temperature, it seems that either route (ii) or (iii) is in play. A detailed computational study 19 suggests that route (ii) is the most viable, involving intermediates as shown in Scheme 9. For computational convenience, the PPh 3 ligands were exchanged for PMe 3 ligands.…”

Experimental and DFT Study of the [AuAr(AsPh3)]-Catalyzed cis/trans Isomerization of [PdAr2(AsPh3)2] (Ar = C6F5 or C6Cl2F3): Alternative Mechanisms and Its Switch upon Pt for Pd Substitution

“…[22][23][24][25][26][27][28] The transmetalation reaction has been studied in some cases by computational methods, but experimental quantitative data are scarce. [29][30][31][32][33] In 2012 we reported a kinetic and computational study on the Rf/Cl exchange (transmetalation) between [PdRf2L2] and [AuClL] (L = AsPh3). 29 In that work we proposed that [AuClL], acting as "incoming ligand", substituted one L ligand at the palladium complex; at that step the transition state displayed a Pd-Au interaction.…”

“…In the last years, many examples of coupling reactions involving R-for-X Pd/Au transmetalations have been reported, in which organogold complexes participate as stoichiometric reagents, − or are used as cocatalyst. − The transmetalation reaction has been studied in some cases by computational methods, but quantitative experimental data are scarce. − In 2012, we reported a kinetic and computational study on the Rf/Cl exchange (transmetalation) between [PdRf 2 L 2 ] and [AuClL] (L = AsPh 3 ) . In that work, we proposed that [AuClL], acting as “incoming ligand”, substituted one L ligand at the palladium complex; at that step, the transition state displayed a Pd–Au interaction.…”

“…This pathway was soon backed by the proposal of Hashmi for the vinyl/X transmetalation between [PdRXL 2 ] and [Au­(vinyl)­L] (L = PMe 3 ), which additionally demonstrated a small increase in Δ G ‡ on moving from X = I to X = Cl . A computational study of the transmetalation of alkynylgold complexes to palladium was reported more recently by Larsen and Nielsen, in a work concerning the Au/Cu/Pd cocatalyzed Sonogashira reaction . Other computational studies on Au/Pd transmetalations and Pd complexes have been recently published by Yates. , Note that none of these studies deals with the simultaneous exchange of two organic groups between gold and palladium (i.e., R-for-R′ Pd/Au exchange).…”