Chemodivergent Dehydrative Nucleophilic Substitutions of Diarylmethanols with 1‐Phenyl‐1H‐tetrazole‐5‐thiol Catalyzed by FeCl₃

Abstract

Chemodivergent dehydrative nucleophilic substitutions of diarylmethanols with 1‐phenyl‐1H‐tetrazole‐5‐thiol were achieved using FeCl3 as a catalyst in MeNO2 by changing reaction temperature. It was found that sulfur nucleophilic attack occurred to afford kinetically controlled products that rearranged into thermodynamically controlled products. A variety of diarylmethanols could be applied to the reaction, irrespective of the substituents on the aromatic rings of the substrates. It was also revealed that the reactions of several kinds of alkyl‐ and heteroaryl‐substituted benzyl alcohols gave moderate to good product yields. The controlled experiments performed revealed that both reactions proceeded in an SN1 fashion and heating with a Lewis acid was necessary for rearrangement.

Lewis Acid Catalysed Chemoselective Amination of Alcohols Using Heterocyclic Thiones: An Avenue to Thiotetrazole Derivatives

“…Diphenylmethanol carrying −Me substituent at the para position furnished excellent result. Conversely, diphenylmethanol bearing −Cl substituent at the para position, shows a declining trend in reactivity that can be attributed to the carbocation intermediates being destabilised due to the electron‐withdrawing nature of the Cl substituent [9] (Table 2 , 3 b – c ). Another para substituted −Cl atom on one of the aromatic rings of diphenylmethanol yielded moderate results (Table 2, 3 d ).…”

“…Reaction mechanism : To gain insight into the novel transformation, mechanistic studies have been conducted. On the basis of literature reports, [9] a plausible mechanism has been proposed (Scheme 3). Initially, in presence of Cu(OTf) 2 dehydration of diphenylmethanol generates carbocation (step II).…”

“…[6][7][8] It is well known to function both as sulphur and nitrogen nucleophiles. [9] Owing to ambident nucleophilic nature of thiotetrazoles, the development of chemoselective amination is a difficult task. Recently, direct dehydrative nucleophilic substitutions using free alcohols as substrates catalysed by Lewis and Brønsted acids have attracted much attention in organic synthesis.…”

“…However, utility to form C−N bond is rare [6–8] . It is well known to function both as sulphur and nitrogen nucleophiles [9] . Owing to ambident nucleophilic nature of thiotetrazoles, the development of chemoselective amination is a difficult task.…”

“…Successful amination of tert‐ butyl group with thiotetrazoles which was unexplored in previous methodologies yield excellent results under our protocol. Restricting to only secondary alcohols, very recently Nakata's group [9] has reported both N‐ and S‐ arylation in presence of FeCl 3 catalyst (Scheme 1(1c)). So far only few synthetic methodologies have been developed for amination of alcohols using heterocyclic thiones.…”