Regioselective Formation of Enol Esters from the Ruthenium-Catalyzed Markovnikov Addition of Carboxylic Acids to Alkynes

Abstract

The ruthenium complexes [Ru(CO)2(P(p-C6H4-X)3)2(O2CPh)2] (1a, X = CF3; 1b, X = Cl; 1c, X = H; 1d, X = Me; 1e, X = OMe) were successfully applied in the regioselective Markovnikov addition of carboxylic acids to terminal alkynes, yielding valuable enol esters. Catalyst screening revealed a significant influence of phosphine's electronic nature on activity and selectivity. The highest activity was achieved with catalyst 1a, featuring the most electron-withdrawing phosphine ligand. Selectivity and activity could be further improved by the addition of catalytic amounts of AgOTf. Moreover, excellent selectivities with up to 99% of the Markovnikov product were achieved. The electronic influence of the substrates on the reaction rate was quantified by Hammett plots. By the use of electron-rich alkynes or highly acidic carboxylic acids, the reaction rate could be increased. Hence, the addition of highly acidic pentafluorobenzoic acid to electron-rich 4-methoxyphenylacetylene can even be carried out quantitatively at 25 °C within 4 h. Furthermore, a broad range of simple as well as electronically or sterically challenging substrates could be isolated in good to excellent yields with high regioselectivity and under mild reaction conditions (25-70 °C). The best reported activities and selectivities were obtained for the conversion of aromatic alkynes.

Ruthenium‐Catalyzed Hydrocarboxylation of Internal Alkynes

“…[40][41][42] By applying 1.0 mol-% of catalyst 1, a conversion of 70 % was reached after 6 h at 140°C (Table 1, Entry 1). [42] Figure 1. [43] Relative to our previously reported protocol for the conversion of terminal alkynes, higher reaction temperatures were required due to the increased activation energy.…”

“…Interestingly, this reaction led to the formation of (E)-2a as the exclusive product. [23,25,36,38,42] To improve the activity, the impact of diverse additives (1.0 mol-%) was examined (Table 1). [42] Figure 1.…”

“…[40][41][42] In continuing these studies, we have investigated the catalytic activity of 1 for hydrocarboxylation of challenging internal alkynes. [40][41][42] In continuing these studies, we have investigated the catalytic activity of 1 for hydrocarboxylation of challenging internal alkynes.…”

“…Recently, we demonstrated that the mononuclear ruthenium complex [Ru(CO) 2 {P(p-CF 3 -C 6 H 4 ) 3 } 2 (O 2 CPh) 2 ] (1) is a highly efficient and selective catalyst for the addition of carboxylic acids to terminal alkynes and propargylic alcohols under mild reaction conditions. [40][41][42] In continuing these studies, we have investigated the catalytic activity of 1 for hydrocarboxylation of challenging internal alkynes. Herein, the effect of catalytic amounts of various additives on reaction efficiency and selectivity as well as substrate scope is explored and discussed.…”

The intermolecular hydro-oxycarbonylation of internal alkynes: current state of the art

“…72,73 In this regard, in combination with the Lewis acid B(C6F5)3, complex 5 was able to catalyze the addition of different carboxylic acids to both activated and unactivated internal alkynes with complete syn-selectivity, affording a broad range of trisubstituted (E)-enol esters in high yields (Scheme 5). 73 Unfortunately, in the case of unsymmetrically substituted substrates, the regioselectivity of the process could not be controlled, and mixtures of the two regioisomeric syn-addition products 6 and 7 were in all the cases obtained.…”