Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone
Tania J. Bellinger,
Teavian Harvin,
Ti’Bran Pickens-Flynn,
Nataleigh Austin,
Samuel H. Whitaker,
Mai Ling C. Tang Yuk Tutein,
Dabria T. Hukins,
Nichele Deese,
Fenghai Guo
Affiliations
Tania J. Bellinger
Department of Chemistry, Winston Salem State University, 601 S. Martin Luther King Jr. Dr., Winston Salem, NC 27110, USA
Teavian Harvin
Department of Chemistry, Winston Salem State University, 601 S. Martin Luther King Jr. Dr., Winston Salem, NC 27110, USA
Ti’Bran Pickens-Flynn
Department of Chemistry, Winston Salem State University, 601 S. Martin Luther King Jr. Dr., Winston Salem, NC 27110, USA
Nataleigh Austin
Department of Chemistry, Winston Salem State University, 601 S. Martin Luther King Jr. Dr., Winston Salem, NC 27110, USA
Samuel H. Whitaker
Department of Chemistry, Winston Salem State University, 601 S. Martin Luther King Jr. Dr., Winston Salem, NC 27110, USA
Mai Ling C. Tang Yuk Tutein
Department of Chemistry, Winston Salem State University, 601 S. Martin Luther King Jr. Dr., Winston Salem, NC 27110, USA
Dabria T. Hukins
Department of Chemistry, Winston Salem State University, 601 S. Martin Luther King Jr. Dr., Winston Salem, NC 27110, USA
Nichele Deese
Department of Chemistry, Winston Salem State University, 601 S. Martin Luther King Jr. Dr., Winston Salem, NC 27110, USA
Fenghai Guo
Department of Chemistry, Winston Salem State University, 601 S. Martin Luther King Jr. Dr., Winston Salem, NC 27110, USA
Grignard reagents undergo conjugate addition to thiochromones catalyzed by copper salts to afford 2-substituted-thiochroman-4-ones, both 2-alkylthiochroman-4-ones and thioflavanones (2-arylthiochroman-4-ones), in good yields with trimethylsilyl chloride (TMSCl) as an additive. The best yields of 1,4-adducts can be attained with CuCN∙2LiCl as the copper source. Excellent yields of 2-alkyl-substituted thiochroman-4-ones and thioflavanones (2-aryl substituted) are attained with a broad range of Grignard reagents. This approach works well with both alkyl and aromatic Grignard reagents, thus providing a unified synthetic approach to privileged 2-substituted thiochroman-4-ones and a potential valuable precursor for further synthetic applications towards many pharmaceutically active molecules. The use of commercially available and/or readily prepared Grignard reagents will expedite the synthesis of a large library of both 2-alkyl substituted thiochroman-4-ones and thioflavanones for additional synthetic applications.
