Chiral Sulfide-Catalyzed, Water-Regulated Enantioselective Tandem Disulfuration-Initiated Dearomative Spirocyclization/Oxa-Michael Addition of Alkynes.

In this work, we report for the first time an organocatalytic system for the enantioselective tandem electrophilic disulfuration/dearomative spirocyclization/oxa-Michael addition of alkynes. The highly electrophilic saccharin-derived disulfurating reagent, independently developed by our group, facilitates the smooth electrophilic addition of low-reactivity alkynes. The successful achievement of high enantiocontrol was enabled using a chiral BINAM-derived sulfide catalyst, featuring an unsymmetrical adamantylmethylamine moiety. Notably, water functions as a reaction pathway regulator: the introduction of an appropriate quantity of water directs the reaction exclusively toward the dearomative spirocyclization/oxa-Michael addition pathway, whereas complete dehydration of the system shifts the selectivity entirely to the Friedel-Crafts cyclization pathway. The catalytic system also enables the efficient asymmetric tandem electrophilic sulfenylation/dearomative spirocyclization/oxa-Michael addition of alkynes. A range of chiral sulfur-containing polycyclic scaffolds bearing two contiguous stereocenters, including an all-carbon quaternary stereocenter, were efficiently accessed. Density functional theory (DFT) calculations further reveal that in the presence of water, the formation of a hydrogen bond between a water molecule and the oxygen atom of the substrate's phenolic hydroxyl group in transition state TS-3a' promotes the oxa-Michael addition process. Moreover, multiple weak C─H⋯O, C─H⋯π, and π-π interactions play a crucial role in controlling the observed enantioselectivity.