Harnessing sulfur and nitrogen in the cobalt(iii)-catalyzed unsymmetrical double annulation of thioamides: probing the origin of chemo- and regio-selectivity† † Electronic supplementary information (ESI) available: Detailed experimental procedures, characterization (1H, 13C and 19F NMR, FTIR and HRMS) data, photophysical properties, X-ray crystallographic data (CIF), coordinates (x,y,z), energies (Hartree) and imaginary frequencies (cm−1) of the computed species for DFT calculations, and 1H, 13C and 19F NMR spectra of the compounds (PDF). CCDC 2045975–2045977. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/d1sc00765c

ABSTRACT: An unconventional cobalt(iii)-catalyzed one-pot domino double annulation of aryl thioamides with unactivated alkynes is presented. Sulfur (S), nitrogen (N), and o,o′-C–H bonds of aryl thioamides are involved in this reaction, enabling access to rare 6,6-fused thiopyrano-isoquinoline derivatives. A reverse ‘S’ coordination over a more conventional ‘N’ coordination of thioamides to the Co-catalyst specifically regulates the formation of four [C–C and C–S at first and then C–N and C–C] bonds in a single operation, a concept which is uncovered for the first time. The power of the N-masked methyl phenyl sulfoximine (MPS) directing group in this annulation sequence is established. The transformation is successfully developed, building a novel chemical space of structural diversity (56 examples). In addition, the late-stage annulation of biologically relevant motifs and drug candidates is disclosed (17 examples). The preliminary photophysical properties of thiopyrano-isoquinoline derivatives are discussed. Density functional theory (DFT) studies authenticate the participation of a unique 6π-electrocyclization of a 7-membered S-chelated cobaltacycle in the annulation process. A Co-catalyzed one-pot double annulation of sulfoximine bearing thioamides with alkynes for the synthesis of [6,6]-fused thiopyrano-isoquinolines is disclosed. The annulation involves a 6π-electrocyclization of 7-membered S-chelated cobaltacycle.

SUBMITTER: Shankar M 

PROVIDER: S-EPMC8115082 | biostudies-literature |

REPOSITORIES: biostudies-literature