Palladium(0)-Catalyzed Anti-Selective Addition-Cyclizations of Alkynyl Electrophiles

Palladium(0)/monophosphine complexes catalyze anti-selective alkylative, arylative, and alkynylative cyclizations of alkynyl electrophiles with organometallic reagents. The remarkable anti-selectivity results from novel oxidative addition, that is, the nucleophilic attack of electron-rich palladium(0) on the electrophile across the alkyne followed by transmetalation and reductive elimination ("anti-Wacker"-type cyclization). With regard to 5-alkynals, triphenylphosphine (PPh3)-ligated palladium(0) catalyzes the cyclization of terminal alkynes and conjugated alkenyl- or alkynyl-substituted ones to afford 2-cyclohexen-1-ol and 2-alkylidene-cyclopentanol derivatives, respectively. For 6-alkyl- or 6-aryl-5-alkynals, the cyclization does not proceed with the palladium/PPh3 catalyst; however, it does proceed with palladium/tricyclohexylphosphine (PCy3), to yield the former products predominantly. Remarkably, the latter catalyst completely switches the regioselectivity in the cyclization of the conjugated diyne-aldehydes. Notably, palladium/PPh3-catalyzed cyclizations also proceed with other organometallics or even without them.