Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Sep-Oct;11(5):900-6.
doi: 10.1021/cc9000604.

Solution-phase parallel synthesis of a multi-substituted benzo[b]thiophene library

Chul-Hee Cho  1 , Benjamin Neuenswander, Gerald H Lushington, Richard C Larock
Affiliations

Solution-phase parallel synthesis of a multi-substituted benzo[b]thiophene library

Chul-Hee Cho et al. J Comb Chem. 2009 Sep-Oct.

Abstract

Generation of a library using parallel syntheses of multi-substituted benzo[b]thiophenes is described. The requisite 3-iodobenzo[b]thiophenes are readily prepared in excellent yields from various alkynes bearing electron-rich aromatic rings by electrophilic cyclization using I(2) in CH(2)Cl(2). The heteroaromatic carbon-iodine bonds allow further diversification by palladium-catalyzed Suzuki-Miyaura, Sonogashira, Heck, and carboalkoxylation chemistry to give multi-substituted benzo[b]thiophene derivatives.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Chemical structures of raloxifene (1), arzoxifene (2), combretastatin A-4 (3), and 3-aroyl-2-aryl-6-methoxybenzo[b]thiophene analogues 4
Figure 2
Figure 2
3-Iodobenzo[b]thiophene library 8{1-18}
Figure 3
Figure 3
Boronic acid 9{1-20} sublibrary
Figure 4
Figure 4
Terminal alkyne 10{1-14} sublibrary
Figure 5
Figure 5
Styrene 11{1-5} and alcohol 12{1-2} sublibrary
Scheme 1
Scheme 1
Scheme 2
Scheme 2
Scheme 3
Scheme 3
Scheme 4
Scheme 4
Scheme 5
Scheme 5
Method A (Suzuki-Miyaura coupling): 10 mol % Pd(PPh3)4, K2CO3 (2.5 equiv), (Het)ArB(OH)2 (9, 1.5 equiv), toluene/EtOH/H2O (20/5/1), reflux; Method B (Sonogashira coupling): 3 mol % PdCl (PPh3)2, 3 mol % CuI, Et2NH, R5C≡CH (10, 1.2 equiv), DMF, 100 °C, 20 min, using microwave irradiation; Method C (Heck coupling): 5 mol % Pd(OAc)2, n-Bu NI (1.0 equiv), Na2CO3 (2.5 equiv), R5CH=CH2 (11, 1.2 equiv), DMF, 80 °C; Method D (carboalkoxylation): CO (1 atm), 3 mol % Pd(OAc)2, 5 mol % dppf, TEA (2.0 equiv), R5OH (12, 1.5 equiv), DMF, 70 °C.
See this image and copyright information in PMC

References

    1. An HY, Cook PD. Chem. Rev. 2000;100:3311–3340. - PubMed
    1. Sun CM. Comb. Chem. High Throughput Screening. 1999;2:299–318. - PubMed
    1. Merritt AT. Comb. Chem. High Throughput Screening. 1998;1:57–72. - PubMed
    1. Goodnow RA, Jr., Guba W, Haap W. Comb. Chem. High Throughput Screening. 2003;6:649–660. - PubMed
    1. Schuffenhauer A, Popov M, Schopfer U, Acklin P, Stanek J, Jacoby EC. Comb. Chem. High Throughput Screening. 2004;7:771–781. - PubMed

Publication types