Ligand effects in homogeneous Au catalysis.

ion agent (entry 4). Echavarren examined the intramolecular hydroarylation of alkynes with indoles, observing that the regioselectivity (formal 7-exo-dig vs 8-endo-dig) of the cyclization is highly dependent upon the catalytic Au source (Table 8). In the cyclization of 37, Ph3PAuCl/AgSbF6 resulted in little discrimination between the pathways leading to 38 and 39 (entry 4). Remarkably, AuCl and AuCl3 overwhelmingly provided the eight-membered ring product 39 (entries 2 and 3). Diametrically, isolable complex 40 featuring a Buchwaldtype ligand provided exclusively the seven-membered ring product 38 (entry 1). Such cationic Au acetonitrile complexes provide an additional isolable, stable alternative to the in situ generation of cationic Au complexes from phosphinegold(I) chloride and silver salts. 3.1.3.2. Enol Nucleophiles. In 2004, Toste reported the 5-exo-dig addition of -ketoesters to alkynes catalyzed by triphenylphosphinegold(I) chloride and silver triflate.Au(III) chloride led to complete consumption of the starting material, but furnished only 30% of the desired product. The cationic Au source initially used by Hayashi/Ito, [(CyNC)2Au]PF6, provided no catalytic activity. Yang demonstrated that thiourea-supported Au(I) chloride complexes also catalyzed the cyclization reaction upon treatment with AgOTf, albeit far more slowly. Sawamura observed remarkable rate accelerations when triethynylphosphine-ligated Au(I) catalysts were used for 6-exo-dig -ketoester additions, as in the cyclization of 41 to 42 (Table 9, entries 5 and 6). It was proposed that a decrease in the entropy of activation, enforced by the “holey catalytic environment” of the ligand, was the source of increased catalytic activity in the cyclization. The triflimide (NTf2) anion employed by Sawamura was initially used in Au catalysis by Gagosz, and generally behaves similarly to other weakly or noncoordinating counterions. One key difference is that phosphinegold(I) triflimide salts are isolable and bench stable, in contrast to other cationic Au salts (i.e., SbF6, BF4, OTf), providing a preparative advantage. An analogous cationic Au(I)-catalyzed reaction using electronrich alkenes, rather than 1,3-dicarbonyls, as the nucleophiles to produce similar products was studied by Echavarren, who found that an array of phosphine ligands were suitable. A striking dimerization reaction was observed by Hashmi while examining the reactivity of o-alkynyl benzyl alcohol 43 with Au catalysts (Scheme 6). Generally, AuCl3 led to Table 7. Hydroarylation of Ynoate 34 entry catalyst T (°C) % yield (Z:E) 1 5% AuCl3/15% AgBF4 60 60 (78:22) 2 5% Ph3PAuCl/AgBF4 60 57 (100:1) 3 3% Ph3PAuCl/BF3 ·Et2O 50 62 (100:1) 4 3% AuCl/DCPB/BF3 ·Et2O 50 71 (100:1) Table 8. 7-exo-dig vs 8-endo-dig Hydroarylation entry catalyst yield (%) 38:39 1 40 82 100:0 2 AuCl3 75 0:100 3 AuCl 70 0:100 4 Ph3PAuCl/AgSbF6 80 1.3:1 Table 9. Rate Acceleration with Tri(ethynyl)phosphine Ligands 3356 Chemical Reviews, 2008, Vol. 108, No. 8 Gorin et al.