Generating Complexity from Simplicity: Pd-Catalyzed or Cu-Promoted Domino Alkyne Homocoupling/Double [2+2] Allenyne Cycloaddition

An efficient Pd-catalyzed or Cu-promoted preparation of attached-ring bis(heterocyclic) fused cyclobutenes in a totally controlled fashion using alkyne homocoupling, as well as a double cyclization of the resulting bis (allenyne) in a domino sequence has been reported. The allene moiety has been developed from almost a rarity to an established member of the weaponry utilized in modern organic synthetic chemistry. The starting allenynes were readily obtained beginning from the appropriate 4-oxoazetidine- 2-carbaldehyde via a regiocontrolled indium-mediated Barbier-type carbonyl-allenylation reaction. No signal for alkenyl cyclobutene protons was detected, indicating that substitution occurred at the former terminal acetylenic end. No loss of stereochemical integrity at the stereogenic centers under the domino conditions has been detected.