Gold-catalyzed intramolecular aminoarylation of alkenes: C-C bond formation through bimolecular reductive elimination.

The utility of homogeneous gold complexes as carbophilic pacids has been well-established, with numerous reports of gold-catalyzed reactions that were initiated by addition of nucleophiles into unsaturated carbon–carbon bonds. Although protodeauration is common, several reactions have been developed in which the resulting organogold intermediate was intercepted. For example, nucleophilic reagents have been employed to intercept cationic organogold intermediates that were derived from reactions with p bonds. In contrast, reactions involving neutral organogold intermediates are terminated by reaction of the resulting carbon–gold bond with an electrophile. Although the electrophile is often a proton, gold(I)-catalyzed carboheterofunctionalization reactions using carbon-based electrophiles have been reported. On the basis of recent reports of goldcatalyzed oxidative transformations, we envisioned that the oxidized analogues of these gold(I) intermediates might also be susceptible to reactive nucleophilic reagents. In line with our efforts in the area of gold-catalyzed hydroamination reactions, we hypothesized that oxidized organogold intermediates that are derived from addition of an amine to a p bond might react with nucleophilic boronic acids in an intramolecular aminoarylation reaction. Whilst our initial studies using allenyl tosylamides were unsuccessful, we were encouraged to find that the Ph3PAuCl-catalyzed reaction of alkenyl tosylamide 1 with excess phenylboronic acid and Selectfluor provided a modest yield of the desired aminoarylation product, 2 (Table 1, entry 1). Using a more cationic gold species, such as Ph3PAuOTf (Table 1, entry 2), led to diminished reactivity. On the basis of our previous observation of counterion effects in gold-catalyzed reactions, we examined the impact of the counterion on the aminoarylation reaction. Whilst the use of Ph3PAuOBz as a catalyst resulted in decreased conversion (Table 1, entry 3), Ph3PAuBr led to a significant increase in the yield of 2 (Table 1, entry 4). The corresponding gold(I) iodide (Table 1, entry 5) provided 2 in only trace amounts, as the iodide itself is likely susceptible to oxidation by Selectfluor. To optimize the reaction further, we sought to identify the active gold species. The combination of either Ph3PAuCl or Ph3PAuBr with Selectfluor and PhB(OH)2 led to the formation of a major signal in the P NMR spectrum at d= 44.28 ppm, which we identified as [(Ph3P)2Au] . Moreover, in situ monitoring of the reaction mixture by P NMR spectroscopy showed this cationic complex to be the dominant gold species in solution during the catalytic reaction; however, independently prepared [(Ph3P)2Au]BF4 was found to produce 2 in inferior yield (Table 1, entry 6) to those obtained when Ph3PAuBr was employed as a catalyst. As strong aurophilic interactions are maintained for Au Au species, we reasoned that the use of bimetallic gold complexes as catalysts might minimize the formation of this type of bisphosphinogold(I) species. We were delighted to find that [dppm(AuBr)2] was an excellent catalyst at room temperature (Table 1, entry 7). The optimized conditions appear to tolerate a wide variety of sulfonamides and to be independent of substitution pattern (Table 2); in addition, trifluoroacetamides are reasonable substrates for the reaction (Table 2, entry 1). The cyclization provides N-protected pyrrolidines at room temperature, even for substrates that do not have the benefit of the Thorpe–Ingold effect (Table 2, entry 2). The ability to form six-membered rings (Table 2, entry 3) is notable, with Table 1: Catalyst screen for the aminoarylation reaction.