Iridium-Catalyzed Diastereo- and Enantioselective [4 + 1] Cycloaddition of Hydroxyallyl Anilines with Sulfoxonium Ylides

Abstract

We present here an iridium-catalyzed diastereo-and enantioselective [4 + 1] cycloaddition reaction of hydroxyallyl anilines with sulfoxonium ylides under mild reaction conditions, leading to 3-vinyl indolines in moderate to good yields with excellent enantioselectivities. Control experiments disclosed a plausible reaction mechanism.

Synthesis of indolines via palladium-catalyzed [4 + 1] annulation of (2-aminophenyl)methanols with sulfoxonium ylides

“…Other Lewis acids, i.e., Zn(OTf ) 2 , Yb(OTf ) 3 , ZnCl 2 , and FeCl 3 , were also tested, and they all successfully promoted reaction efficiency except ZnCl 2 , providing product 3a in 52-76% yields, respectively (Table 1, entries 9-12). Brønsted acids, such as TsOH, MsOH, and TFA, were further examined (Table 1, entries [13][14][15]. The results indicated that all the examined Brønsted acids showed significant promoting effect on the annulation and MsOH was proven to be the optimal acid, furnishing the desired product 3a in 89% isolated yield.…”

“…Thereafter, reductive elimination gives product 3a, with the regeneration of the palladium(0) species. According to previous literature, [11][12][13][14] the [4 + 1] annulation proceeds via the key zwitterionic intermediate C′ to form product 3a (Scheme 2, pathway b), which could not be ruled out, but pathway a is more convincing because it is difficult for the alkylamino group of 1a to form the corresponding amino anion under acidic conditions.…”

“…Formal [n + 1] annulations of sulfoxonium ylides are powerful and versatile tools to construct highly functionalized 3-, 4-, 5-and 6-membered rings. 8-10 Among them, [4 + 1] annulations of 2-functionalized anilines with sulfoxonium ylides as C1 units are promising alternatives to construct indoline derivatives, which have been achieved using palladium, 11 iron, 12 copper, 13 and iridium 14 catalysts (Scheme 1).…”

Recent Advances on the Catalytic Asymmetric Allylic α-Alkylation of Carbonyl Derivatives Using Free Allylic Alcohols

“…In the same year, Sun et al reported the iridium-catalyzed diastereo- and enantioselective [4 + 1] cycloaddition reaction of a wide range of substituted hydroxyallyl anilines with aromatic and aliphatic sulfoxonium ylides 89 (Scheme ). The reaction is a straightforward way to synthesize highly substituted 3-vinyl indolines 91 containing two stereogenic centers in moderate to good yields with good diastereoselectivities (>19:1 dr in all cases) and excellent enantioselectivities. On the basis of experimental results, the reaction is believed to proceed via an AAA process that furnishes intermediate C from the π-allyliridium species B , followed by an intramolecular N -nucleophilic substitution that provides intermediate D and dimethyl sulfoxide.…”