Reversible Oxidative Additions of Weak Acids to Pd(0) Complexes: Effects on Pd–H-Catalyzed Enyne Cycloisomerization

Palladium hydrides are ubiquitous during organometallic reactions. However, synthesis of catalytically active Pd–H from precatalytic Pd, as in Pd–H-catalyzed enyne cycloisomerization, is often thermodynamically unfavorable, producing very little Pd–H. Therefore, the Pd loadings required are often high due to the small amount of active catalyst present. We investigated the oxidative addition of weak acids to Pd(0) complexes in an attempt to increase [Pd–H] and shorten reaction times. Pd(PCy3)2 reacts with 1,1'-binaphthyl-2,2'-diol (BINOL) and acetic acid reversibly, to produce Pd–H. We measure the equilibrium constants and show that the rate of the cycloisomerization of 1 increases at higher [ROH]. By increasing [ROH], we can lower the Pd(PPh3)4 loading by 50 times with reasonable reaction times. BINOL-derived phosphoric acids, such as S-TRIP, gave irreversible oxidative additions to Pd(PCy3)2 and also resulted in high enantioselectivities. This work demonstrates that it is possible to use the Pd more efficiently in such reactions by maintaining a high concentration of the weak acid in the reaction, resulting in higher concentrations of the catalytically active Pd–H species. More broadly, we show that for reactions involving in situ formation of active catalytic intermediates, both the number of equivalents of ligands and their concentration are important for improving catalytic activity.