Preparation Of Functionalized Multi-substituted Cyclic Compounds From Unsaturated Cyclobutanones

Cyclobutane motifs are important building blocks in organic synthesis and medicinal chemistry due to its high torsional strain and unique conformation.The four-membered ring structure is prone to ring opening,resulting in reactive intermediates that can be captured by nucleophiles,enophiles,and unsaturated bonds.This strain relief strategy makes cyclobutenone a versatile synthon,which has been used in the synthesis of various complex molecules.Among the four-membered ring compounds,the properties of compounds containing saturated carbon-carbon bond structures have been extensively studied,but the four-membered ring compound cyclobutenone containing unsaturated carbon-carbon bonds has been less studied.Alkylation of enols is the basic conversion process to produce tertiary carbon or quaternary carbon compounds.Due to the inherent high tension and high carbonyl electrophilicity of benzocyclobutanone,the carbon-carbon bond cleavage reaction under various conditions has been extensively studied.However,the enolization reaction of benzocyclobutanone will produce an anti-aromatic intermediate,and the alkylation reaction of such intermediates has not been reported.We reported here a facile synthesis of dibenzocyclooctadiones via dimerization of benzocyclobutenones in the presence of simple base via the elusive benzocyclobutenone anions.The temperature effect played a crucial role in the dimerization reaction.Further synthesis of 5,11-disubstituted dibenzo[a,e]cyclooctatetraene from dibenzocyclooctadione was also explored.The enantioselective synthesis of cyclobutane has always been an attractive and challenging subject,and the functionalization of cyclobutenone is a less studied strategy.A copper-catalyzed tandem process to generate chiral cyclobutene derivatives has been developed.It is based on an enantioselective conjugate addition of a cyclobutenone and sequential trapping with a chlorophosphite in a one-pot process.These phosphates are stable under mildly acidic conditions and serve as good electrophiles in Negishi coupling reactions.