Hetero-Type Benzannulation Leading to Substituted Benzothio-Phenes

Taro Kono; Ryosuke Sasaki; Hideki Goto; Masatoshi Kakuno; Yoo Tanabe

doi:10.3390/molecules26227008

Hetero-Type Benzannulation Leading to Substituted Benzothio-Phenes

Molecules. 2021 Nov 19;26(22):7008. doi: 10.3390/molecules26227008.

Authors

Taro Kono¹, Ryosuke Sasaki¹, Hideki Goto¹, Masatoshi Kakuno¹, Yoo Tanabe¹

Affiliation

¹ Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan.

Abstract

TiCl₄ (or SnCl₄)-promoted hetero-type benzannulation reactions using various (2,2-dichlorocyclopropyl)(thiophen-2-yl)methanols proceeded smoothly to produce uniquely substituted 4-chlorobenzothiophenes (five examples). The present approach involves the first distinctive thiophene formation from thiophene cores, in contrast to traditional methods of thiophene formation from benzene cores. The stereocongested (less reactive) Cl position in the obtained 4-chlorobenzothiophenes functioned successfully as the partners of three cross-coupling reactions: (i) a Suzuki-Miyaura cross-couplings using Pd(OAc)₂/SPhos/K₃PO₄ catalysis (seven examples; 63-91%), (ii) a hydroxylation using KOH/Pd(dba)₂/tBu-XPhos catalysis (85%), and (iii) a borylation using a B₂(pin)₂/Pd(dba)₂/XPhos/NaOAc catalysis-provided 4-(pin)B-benzothiophene (58%).

Keywords: Suzuki–Miyaura cross-coupling; benzannulation; benzothiophene; borylation; gem-dichlorocyclopropane; hydroxylation; thiophene; tin tetrachloride; titanium tetrachloride.