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. 2018 Jul 15;23(7):1728.
doi: 10.3390/molecules23071728.

Development of Conjugate Addition of Lithium Dialkylcuprates to Thiochromones: Synthesis of 2-Alkylthiochroman-4-ones and Additional Synthetic Applications

Shekinah A Bass  1 , Dynasty M Parker  2 , Tania J Bellinger  3 , Aireal S Eaton  4 , Angelica S Dibble  5 , Kaata L Koroma  6 , Sylvia A Sekyi  7 , David A Pollard  8 , Fenghai Guo  9   10
Affiliations

Development of Conjugate Addition of Lithium Dialkylcuprates to Thiochromones: Synthesis of 2-Alkylthiochroman-4-ones and Additional Synthetic Applications

Shekinah A Bass et al. Molecules. .

Abstract

Lithium dialkylcuprates undergo conjugate addition to thiochromones to afford 2-alkylthiochroman-4-ones in good yields. This approach provide an efficient and general synthetic approach to privileged sulfur-containing structural motifs and valuable precursors for many pharmaceuticals, starting from common substrates-thiochromones. Good yields of 2-alkyl-substituted thiochroman-4-ones are attained with lithium dialkylcuprates, lithium alkylcyanocuprates or substoichiometric amount of copper salts. The use of commercially available inexpensive alkyllithium reagents will expedite the synthesis of a large library of 2-alkyl substituted thiochroman-4-ones for additional synthetic applications.

Keywords: 2-alkylthiochroman-4-ones; conjugate addition; lithium dialkyl cuprates; thiochroman-4-ones; thiochromones.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Structures of Thiochromanone, Thioflavone, Thiochromone, and Thioflavanones.
Figure 1
Figure 1
Conjugate Addition of Lithium Dialkylcuprates to Thiochromones.
Scheme 2
Scheme 2
The Scope of Lithium Dialkylcuprates in Conjugate Addition to Thiochromone. a. All the reactions were performed using 1.2 equivalentof R2CuLi in the presence of 2.0 equivalent of TMSCl unless noted otherwise. b. RLi were commercially available. c. Yields are based on isolated products by flash column chromatography. d. Reactions were stirred for 12 h and warm up to room temperature before work up.
Scheme 3
Scheme 3
Reactions of Lithium di-n-butylcuprates with Substitututed Thiochromones. a. All the reactions were performed using 1.2 equivalentof n-Bu2CuLi in the presence of 2.0 equivalent of TMSCl unless noted otherwise. b. n-BuLi is commercially available. c. Yields are based on isolated products by flash column chromatography. d. Reactions were stirred for 12 h and warm up to room temperature before work up.
Scheme 4
Scheme 4
Synthetic Applications of 2-n-butyl Thiochroman-4-one.
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