Rotational Selectivity in Cyclobutene Ring Openings. Model Studies Directed toward a Synthesis of Verrucarin A

Article abstract of DOI:10.1021/jo00177a015

The rotational selectivity in the opening of dissymmetric cyclobutenes to the corresponding dienes is described.In the opening of the monoesters of cis-3,4-cyclobutenedicarboxylic acid, an unusual solvent effect on the ring opening is noted.Switching from Me2SO to 1,2-dichloroethane leads to a 3:1 ratio of the (E,Z)-muconates, favoring the ester on the E double bond.The two isomers can be differentiated by 13C NMR spectroscopy in which the above isomer shows a Δδ for the α,α' carbons of only ca. 2.5 ppm but a Δδ of 5-6 ppm for the isomer having the ester on theZ double bond.Inclusion of the cyclobutene as part of a macrotriolide related to verrucarin A imparts conformational control on the rotational selectivity to favor the E,Z isomer corresponding to the natural products.These relatively simple models inhibit protein synthesis in a fashion reminiscent of the natural products.