Copper(i) chloride promoted Csp²–N cross-coupling of 1,2-di(pyrimidin-2-yl) disulfides with amines: an efficient approach to obtain C2-amino functionalized pyrimidines

Abstract

The copper(i)-promoted cross-coupling of 1,2-di(pyrimidin-2-yl) disulfides with aromatic amines and aliphatic amines to deliver C-N coupling products in moderate to good yields is reported in this paper. Central to this strategy is the conversion of disulfides into aryl- and alkyl amines by a copper-promoted chemoselective C-S bond cleavage.

C‐O and C‐S coupling reaction of 1,2‐di(pyrimidin‐2‐yl) disulfides with phenols/thiophenols promoted by copper(I) chloride

“…Recently, we reported that CuCl[10e] and Cu(OAc) 2 ·H 2 O (20 mol%)/NaAsc (30 mol%) catalyst systems promoted the C‐N cross‐coupling reaction of di(hetero)aryl disulfides and aryl halides with amines or amides. So, we tested the CuCl and CuSO 4 ·H 2 O (100 mol%)/NaAsc (200 mol%) promoter systems in the C‐O coupling of 1,2‐di(pyrimidin‐2‐yl) disulfides 1a and phenol 2a (Table ).…”

“…Subsequently, the complex A reacts with phenol producing the intermediate species B , which subsequently undergoes reductive cleavage of the C‐S bond giving the C‐O coupling product 3a . [10b‐f]…”

“…Di(hetero)aryl disulfides are widely used as electrophiles instead of aryl halides for the construction of C‐S bond through S‐S bond cleavage,[8] because that disulfides are structurally symmetrical, air stable, and easy to handle [9]. Recently, we developed a series of method to construct C‐C, C‐N, and C‐S bonds through C‐S and S‐S bonds cleavage of di(hetero)aryl disulfides with various nucleophiles including aryl boronic acids, alkynes, Grignard reagents, and amines [10]. The obtained products tetra‐substituted pyrimidines display wide pharmacological and biological properties[11] In continuation of our work in the formation of the C‐C and C‐Z (Z = O, N, S) bond utilizing 1,2‐di(pyrimidin‐2‐yl) disulfide as an electrophile, we investigated the C‐O and C‐S coupling of the di(hetero)aryl disulfides with phenol and aryl thiol using CuCl to obtain oxylated and sulfenylated pyrimidines (Scheme ).…”

Direct construction of sulfenylated pyrazoles catalyzed by I 2 at room temperature

“…In the last few decades, much effort has been devoted to developing new methods for C-S bond construction. Among these approaches, transition-metal catalyzed cross coupling reactions are among the most powerful tools for C-S bond formation [10][11][12][13][14][15][16][17][18]. However, some of these methods require expensive and air-sensitive metal catalysts, and are not environmentally benign.…”

Dehydrosulfurative C–N Cross-Coupling and Concomitant Oxidative Dehydrogenation for One-Step Synthesis of 2-Aryl(alkyl)aminopyrimidines from 3,4-Dihydropyrimidin-1H-2-thiones

“…Despite their biological importance, the synthetic strategy toward these compounds is limited in scope and generality, especially for the rapid generation of a diverse range of such compounds. Usually, the fully substituted 2-aryl­(akyl)­aminopyrimidines are obtained by nucleophilic aromatic substitution or metal-catalyzed C–N cross-coupling of pyrimidines containing halides or other leaving groups at the C2 position with amines, most of which require synthesis of pyrimidine partners in multiple steps from 3,4-dihydropyrimidin-1 H -2-thiones (DHPMs) or related starting materials. − Herein, we report a one-step synthesis of fully substituted 2-aryl­(alkyl)­aminopyrimidines from DHPMs via dehydrosulfurative C–N cross-coupling and concomitant oxidative dehydrogenation under a Pd/Cu catalytic system.…”