Access to Substituted Thiophenes through Xanthate-Mediated Vinyl C(sp²)-Br Bond Cleavage and Heterocyclization of Bromoenynes

Abstract

An environmentally sustainable strategy for the chemoselective heterocyclization of bromoenynes through a transition-metal-free sulfuration/cyclization process is reported. Using inexpensive and safe EtOCS 2 K as a thiol surrogate and tetrabutylphosphonium bromide and H 2 O as a mixed solvent, the reaction provided a range of substituted thiophenes in moderate to good yields. In addition, 2,3,4,5-tetrasubstituted thiophenes were able to be prepared under mild reaction conditions by electrophilic heterocyclization with NH 4 I and EtOCS 2 K in good yields.

Metal‐Catalyzed Haloalkynylation Reactions

“…[51] One recent example uses the Pd-catalyzed [16,28] and the Au-catalyzed bromoalkynylation [36] of alkynes for the synthesis of bromoenynes 45, which deliver highly substituted thiophenes (60 and 61) via a chemoselective heterocyclization (Scheme 27). [49] Other examples include the application of haloenynes for the synthesis of cyclic enediynes [52] and pentalenes. [53]…”

“… Chemoselective heterocyclization of bromoenynes 45 via a transition‐metal‐free sulfuration/cyclization process to the thiophenes 60 and 61 . TBPB=tetrabutylphosphonium bromide [49] …”

Synthesis of 3‐Amino‐4‐iodothiophenes through Iodocyclization of 1‐(1,3‐Dithian‐2‐yl)propargylamines

“…Another approach to 3‐iodothiophenes was provided with ( Z )‐thiobutenynes in the presence of iodine or CuSO 4 ⋅ 5H 2 O and NaI mixture which forms CuI 2 in situ (Scheme 1b) [8,9] . Very recently, iodocyclization of enynyl‐substituted xanthate derivatives generated in situ from bromoalkenynes and potassium xanthate was reported for the synthesis of multisubstituted iodothiophenes in good yields, albeit at very high temperature (Scheme 1c) [10] . However, none of these studies offers a direct route to 3‐iodothiophenes containing amino substituents.…”

“…[8,9] Very recently, iodocyclization of enynyl-substituted xanthate derivatives generated in situ from bromoalkenynes and potassium xanthate was reported for the synthesis of multisubstituted iodothiophenes in good yields, albeit at very high temperature (Scheme 1c). [10] However, none of these studies offers a direct route to 3-iodothiophenes containing amino substituents.…”

Programmed Synthesis of Tetra-Aryl Thiophenes with Stepwise, Ester-Controlled Regioselectivity

“…In past literature reports, tetra-aryl thiophenes are obtained either by cyclization of the thiophene moiety or by substitutions on a thiophene backbone. Cyclization methods − involve the lengthy synthesis of structurally complex starting materials and are not adapted for late-stage functionalization. Methods that involve stepwise arylations of a thiophene backbone are therefore more attractive, but face inherent challenges in the arylation of each position in a selective and controlled manner.…”