3-Alkenylation or 3-Alkylation of Indole with Propargylic Alcohols: Construction of 3,4-Dihydrocyclopenta[b]indole and 1,4-Dihydrocyclopenta[b]indole in the Presence of Different Catalysts

Abstract

3-Alkenylation or 3-alkylation of indole with propargylic alcohols could be efficiently controlled by the catalyst. In the presence of triflic acid, 3-alkenylation of indole occurred and a 3,4-dihydrocyclopenta[b]indole skeleton was effectively constructed in moderate to excellent yields via a cascade process. In the presence of Cu(OTf)(2), 3-alkylation of indole resulted in the formation of 3-propargylic indole, which could be further converted into 2-iodo-1,4-dihydrocyclopenta[b]indoles in the presence of N-iodosuccinimide and boron trifluoride etherate. Possible mechanisms related to the 3-alkenylation or 3-alkylation of indole and their extension to the formation of 3,4-dihydrocyclopenta[b]indoles or 1,4-dihydrocyclopenta[b]indoles are postulated and discussed.

Synthesis of Iodine‐Substituted Quinolines, Quinolinium Salts, and Isoquinolinium Salts via a Three‐Component Tandem Reaction of Aryl Azides, Propargylic Alcohols, and Iodine

“…In the case of propargylic alcohols, the sp 2 carbocation (C1) and sp carbocation (C3) are competitive . When 1,3‐diaryl propargylic alcohols were used in this reaction, reactions at C1 were more favored for steric and electronic reasons.…”

Regioselective Direct C‐Alkenylation of Indoles

“…Reaction of indoles with propargylic alcohols in the presence of trifluoromethanesulfonic acid (TfOH) follows a different mechanism leading to 3,4‐dihydrocyclopentaindoles as main products (Scheme ) . In this case, the acid causes a protonation of the allenyl intermediate 20 generating a stabilized allylic carbocation 21 which reacts intramolecularly with the indole ring leading to the final products.…”

“…Reaction of indoles with propargylic alcohols in the presence of trifluoromethanesulfonic acid (TfOH) follows ad ifferent mechanism leading to 3,4-dihydrocyclopentaindoles as main products (Scheme 32). [87] In this case, the acid causes ap rotonation of the allenyli ntermediate 20 generating as tabilized allylic carbocation 21 which reacts intramolecularly with the indole ring leading to the final products.I nt he same reaction as imple propargylation is observed when TfOH is substituted by ac atalytic amount of Cu(OTf) 2 .T he obtained 3-propargylindoles can be treated with N-iodosuccinimide exploiting a 5endo-trig ring closure which affords regioisomeric1 ,4-dihydrocyclopentaindoles in low to moderate yields (16-54 %).…”

CH Functionalization/CO Bond Cleavage of Benzyl Silyl Ethers with Ynamides for the Chemoselective Synthesis of Skeletally Diverse Compounds

“…When the reaction of 1c and indole‐derived ynamide 2i were performed, the corresponding indene was not observed. Instead, the reaction afforded allene 4 in 45% yield,14 probably because the indole moiety was more nucleophilic than the carbon‐carbon triple bond (Scheme ) 15…”