Accessing Unsymmetrically Linked Heterocycles through Stereoselective Palladium-Catalyzed Domino Cyclization
Ramon Arora
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 Canada
Search for more papers by this authorDr. José F. Rodríguez
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 Canada
Search for more papers by this authorDr. Andrew Whyte
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 Canada
Search for more papers by this authorCorresponding Author
Prof. Mark Lautens
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 Canada
Search for more papers by this authorRamon Arora
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 Canada
Search for more papers by this authorDr. José F. Rodríguez
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 Canada
Search for more papers by this authorDr. Andrew Whyte
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 Canada
Search for more papers by this authorCorresponding Author
Prof. Mark Lautens
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 Canada
Search for more papers by this authorGraphical Abstract
Solving alkynes of problems with palladium. A palladium-catalyzed domino cyclization of alkyne-tethered carbamoyl chlorides and aryl iodides with alkyne-tethered aryl nucleophiles is reported. This methodology unsymmetrically links heterocycles along a tetrasubstituted olefin with >20:1 E/Z selectivity and up to 96 % yield.
Abstract
A palladium-catalyzed strategy is presented to synthesize unsymmetrically linked heterocycles within stereoselective tetrasubstituted olefins. This reaction is proposed to occur via a vinyl-PdII intermediate capable of initiating the cyclization of various alkyne-tethered nucleophiles. Products are formed in up to 96 % yield and excellent stereoselectivities are obtained using low catalyst loadings. This transformation was scalable up to 1 mmol and mechanistic studies suggest a syn-carbopalladation of the carbamoyl chloride followed by PdII-catalyzed cyclization of alkyne-tethered nucleophiles.
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