Dehydrative Nazarov-type electrocyclizations of alkenyl (hetero)aryl carbinols via calcium catalysis: Access to cyclopenta[b]thiophenes and indene derivatives

• Published in: Tetrahedron 2017-07, Vol.73 (29), p.4093-4108
• Main Authors: Martin, M. Cynthia, Sandridge, Matthew J., Williams, Corey W., Francis, Zola A., France, Stefan
• Format: Article
• Language: English
• Subjects: Calcium catalysis; Carbinols; Cyclopentathiophenes; Electrocyclization; Heterocycles; Nazarov cyclizations
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2017.03.041

A general approach to the understudied cyclopenta[b]thiophenes is reported. The products were directly generated from calcium-catalyzed, dehydrative, Nazarov-type electrocyclizations of alkenyl thienyl carbinols in up to 82% yield. The thienyl carbinols demonstrated good tolerance for aryl and heteroaryl substituents on the alkene. Aryl carbinols were also amenable to the calcium-catalyzed conditions and afforded indene derivatives in good yields. In most cases, the reaction was selective for the thermodynamic alkene isomer; however, substituent effects played a role in determining product outcomes. Mechanistically, the calcium catalyst initiated formation of alkenyl (hetero)aryl carbinyl cations which subsequently underwent a 4π electrocyclization and elimination that is reminiscent of the Nazarov reaction. This transformation is significant for two main reasons: 1) it represents one of the only examples of catalysis for dehydrative, Nazarov-type electrocyclizations in which thiophene was compatible; 2) it allowed for the direct formation of cyclopenta[b]thiophenes while circumventing the need for cyclopenta[b]thiophenones as precursors. [Display omitted]