Synthesis of a Bent, Twisted, and Chiral Phenanthrene via an Iodine Monochloride-Mediated, Strain-Inducing π-Extension Reaction.

A strategy for the synthesis of substituted and strained p-phenylene units is reported. An oxidative allylic alcohol rearrangement, followed by organometallic addition to the resulting α-ketol and subsequent dehydrative aromatization, affords p-terphenyl-containing macrocycles in which the central p-phenylene has been selectively substituted. Ten 18-membered macrocycles have been synthesized, eight of which contain substituents that could enable π-extension. Only alkynylated derivatives were amenable to π-extension via an ICl-mediated reaction, affording a highly bent, twisted, and chiral phenanthrene.

A macrocycle directed total synthesis of di-O-methylendiandrin A.

The total synthesis of the lignan-based cyclobutane di-O-methylendiandrin A has been achieved using diastereoselective, vicinal alkylation and transannular McMurry reactions of a macrocyclic 1,4-diketone as key transformations for establishing relative stereochemistry and furnishing the strained 4-membered ring of the natural product.