S_N1-Type Alkylation of N-Heteroaromatics with Alcohols

Abstract

The organocatalytic alkylation of 2-methyl-N-heteroaromatics with alcohols has been achieved via S1-type C(sp)-H functionalization, providing a green and efficient synthesis of indole and ferrocene-functionalized N-heteroaromatics in high yields.

Atom‐Economic Alk(en)ylations of Esters, Amides, and Methyl Heteroarenes Utilizing Alcohols Following Dehydrogenative Strategies

“…Organocatalysts are advantageous over other methods as they are easily accessible, insensitive towards oxygen and moisture, economical, and non‐toxic. In recent years, the groups of Xiao and Elias have independently described the green and sustainable organocatalytic method for the aforementioned organic transformation [46–47] …”

Brønsted Acid‐Catalysed Dehydrative Substitution Reactions of Alcohols

“…For example, Xiao and co‐workers have established the triflic acid (10 mol %) catalysed alkylation of 2‐methylquinoline with 3‐indolylmethanol 31 in dioxane at 120 °C to give 32 in 93 % yield (Scheme 18). [45] The reaction works for a range of substituted 2‐methylquinoline and 2‐methylquinoxaline derivatives, although the alcohol component is limited to either substituted 3‐indolylmethanols or activated ferrocenylmethanol derivatives. The acid catalyst is thought to promote both enamine formation from the N ‐heterocycle and dehydration of the alcohol electrophile to form a stabilized carbocation.…”

PFOA‐Catalyzed Regioselective Alkylation of Indolylmethanols with 2‐Alkylazaarenes**

“…To be noted, Xiao group reported TfOH catalyzed alkylation of 3‐indolylmethanols in 2017. Nevertheless, 2‐indolylmethanols and the more challenging cross coupling to form highly hindered quaternary centers remain unexplored in their work [23] . As part of our continuing interest in alkylation of 2‐alkylazaarene, [24] we envisaged the following reaction: Reaction of 2‐methylquinoline with readily available 2‐indolylmethanols in the presence of Brønsted acid produced a highly steric quaternary centers (Scheme 1B).…”