Exploiting the σ-phylic properties of cationic gold(i) catalysts in the ring opening reactions of aziridines with indoles

Abstract

A study on the SN2-type ring opening reactions of aziridines with indoles as nucleophiles is reported. Under gold(i) catalysis a great variety of tryptamine derivatives were prepared in good to excellent yields with complete stereocontrol when chiral aziridines were used. We demonstrated that cationic gold(i) catalysts are superior Lewis acids to the previously reported group 3, 12 and 13 metals in terms of catalyst loading and reaction yields. Moreover, complete regioselectivity was observed for 2-phenyl-N-tosylaziridine; whereas, regioselectivity up to 10 : 1 ratio was observed with 2-methyl-N-tosylaziridine. Finally, a preliminary study on the dearomatization reactions giving rise to pyrroloindolines is also reported.

Gold-Catalyzed Conversion of Highly Strained Compounds

“…In 2016, Rossi and co-workers described the Au(I)-catalyzed ring opening of aryl and alkyl aziridines 540 with nucleophilic indoles 541 (Scheme 88a). 140 Prior to this study, multiple reports detailed the ring opening of aziridines with nucleophilic indoles and Lewis acids such as Zn(OTf) 2 , 141 Sc(OTf) 3 , 142 and Sc(ClO 4 ) 3 . 143 However, only one example highlighted the regioselective ring-opening of 2-alkylaziridines with nucleophilic indoles using excess boron trifluoride.…”

“…138 As shown in Scheme 86, 2-substituted activated aziridines typically undergo nucleophilic attack at the lesshindered aziridine carbon atom to generate 531. 140 In contrast, the ring-opening regioselectivity of nonactivated aziridines is substrate and nucleophile dependent and can occur at either the substituted aziridine carbon (path I) or the unsubstituted aziridine carbon (path II). 139 Nonactivated aziridines containing 1-alkenyl, aryl, and acyl R 2 substituents usually undergo nucleophilic attack at the more substituted or more hindered carbon (path I), while R 2 alkyl substituted substrates mostly undergo attack at the less substituted or less hindered carbon (path II).…”

“…However, for nonactivated aziridines (such as N -aryl and N -alkyl), this process requires strong nucleophiles or acid catalysts . As shown in Scheme , 2-substituted activated aziridines typically undergo nucleophilic attack at the less-hindered aziridine carbon atom to generate 531 . In contrast, the ring-opening regioselectivity of nonactivated aziridines is substrate and nucleophile dependent and can occur at either the substituted aziridine carbon (path I) or the unsubstituted aziridine carbon (path II) .…”

Gold‐Catalyzed Functionalization Reactions of Indole

“…For this reason, in 2016 we proposed a gold(I)-catalyzed procedure to produce tryptamines 79 by ring-opening of N-tosylaziridines 78 (Scheme 30). [91] The regioselectivity of the reaction was complete in the case of aryl-substituted aziridines, whereas the presence of alkyl substituent led to reduced regiochemical control. We proposed that products 79 were formed through SN 2type nucleophilic addition of indole to a gold-activated aziridine of type XXXII, followed by rearomatization and protodeauration of the corresponding intermediate XXXIII.…”

Palladium(II)‐Catalyzed C3‐Selective Friedel–Crafts Reaction of Indoles with Aziridines

“…Firstly, an imidazole‐based zwitterionic salt that acted as an organocatalyst for the ring‐opening reaction of 2‐arylaziridines was reported, which included several examples of indoles as the nucleophile . Furthermore, the ring‐opening reactions of aziridines with indoles to afford tryptamines under cationic gold catalysis and the promotion of a stoichiometric amount of BF 3 ⋅ OEt 2 have also been reported . To the best of our knowledge, there are no examples of 2,2‐disubstituted arylaziridines that undergo ring‐opening reactions with indoles, which would lead to the generation of congested quaternary carbons adjacent to an indole –.…”