Selective Ruthenium‐Catalyzed N‐Alkylation of Indoles by Using Alcohols

Abstract

Alcohols for alkylation! The first homogeneous‐catalyzed N‐alkylations of indoles with aliphatic alcohols proceed under transfer hydrogenation conditions. By the use of the Shvo catalyst and p‐toluenesulfonic acid (PTSA) this atom‐efficient reaction occurs highly selectively with water formed as the only byproduct (see scheme).

Ruthenium‐Catalyzed Cascade N‐ and C(3)‐Dialkylation of Cyclic Amines with Alcohols Involving Hydrogen Autotransfer Processes

“…[10] The in situ generated 8a reacts with the amine to form the iminium ion I which, in the absence of acidic additive, undergoes reduction and gives 4a. However, in the presence of sulfonic acid, as reported earlier by Williams and Beller in the case of indole derivatives, [21] I might rearrange into the iminium ion II via a [1,3] hydride shift. Deprotonation of II might lead to the formation of enamine III as key intermediate.…”

Mechanistic Studies on the Alkylation of Amines with Alcohols Catalyzed by a Bifunctional Iridium Complex

“…The concentration of aniline is higher than that of water, especially in the initial phase of reaction, shifting the equilibrium toward imine formation. Hence, on the basis of experimental studies, we can presume that the imine coordination step (TS 11-12 ) is slightly lower in energy than the alcohol oxidation step (TS [5][6] or TS 2-9 ) in the initial phase of the reaction but becomes competitive eventually, when concentrations have shifted sufficiently to allow back-reaction to alcohol.…”

Improved Ruthenium‐Catalyzed Amination of Alcohols with Ammonia: Synthesis of Diamines and Amino Esters

“…Based on our continuing interest in "borrowing-hydrogen" methodology using alcohols [17] and amines, [18] in a joint cooperation with industry we became involved in a program to extend the substrate scope of alcohol aminations. As a starting point of our investigations we tested the amination of isosorbide with ammonia (Scheme 2).…”