A novel acid-catalyzed C5-alkylation of oxindoles using alcohols

Abstract

A novel C5-alkylation of oxindoles using alcohols as alkylating agents under acid catalysis is described for the first time. The reactions of various benzylic, allylic and propargylic alcohols are studied to obtain the corresponding 5-substituted oxindoles in good yields.

Recent Advances in the Direct Nucleophilic Substitution of Allylic Alcohols through SN1-Type Reactions

“…Interestingly, the alkylation occurs at C5 and not at C3 (αalkylation) as happens when Lewis acids or basic media are employed [Scheme 20, (a)]. 36 In contrast, the α-alkylation of carbonyl compounds, such as aldehydes, was obtained using PTSA under mild reaction conditions with excellent results especially for (E)-1,3-diphenylprop-2en-1-ol (3) [Scheme 20, (b)]. 37,38 The α-alkylation of various aldehydes using alcohol 3 has been also reported using PTSA (20 mol%) with acetonitrile as the solvent in combination with a polysiloxane (10 mol%) bearing a secondary amine in the structure in a dual activation strategy.…”

Highly chemoselective synthesis of dimeric 2-oxindoles with a C-3/C-5′ linkage via Friedel–Crafts alkylations of 2-oxindoles with 3-hydroxy-2-oxindoles

“…However, other metal triflates such as Yb(OTf ) 3 , Zn(OTf ) 2 , a Reactions were carried out on a 0.50 mmol of (±)-6a with 0.50 mmol of 7a in 4 mL of solvent. AgOTf, and Sc(OTf ) 3 afforded products in the range of 53-78% isolated yields (entries [8][9][10][11]. Among the various solvents such as dichloroethane, dichloromethane, chloroform, toluene, xylene, acetonitrile, and tetrahydrofuran, it was observed that dichloroethane is a better choice (entries [13][14][15][16][17][18][19][20].…”

“…The combined organic layers were concentrated under reduced pressure. The crude products were purified by column chromatography using a hexane-EtOAc mixture as the eluent to afford the desired product (11).…”

“…To the best of our knowledge there is no report on utilization of 3-hydroxy 2-oxindole (3°alcohol) as an electron-deficient partner that can be used for F-C alkylations of 2-oxindoles as an electronrich partner. 11 2-Oxindoles such as (±)-4a serve as versatile building blocks in the syntheses of various indole alkaloids of immense biological importance due to their ability to undergo a variety of electrophilic substitution reactions at 1-, 2-and 3-position [red arrows shown in (±)-4a, Fig. 1].…”

Cationic indium catalysis as a powerful tool for generating α-alkyl propargyl cations for SN1 reactions

“…Developing a direct S N 1-like propargylation under mild reaction conditions 34 using readily available propargyl alcohols is a meaningful challenge from the standpoint of reactant compatibility. Many reactant (i.e., secondary alcohols) and nucleophile (arenes, alcohols, thiols, and amides) combinations are incompatible when functional groups are present, such as esters, amides, cyano, and nitro groups.…”