Simultaneous Installation of 1,6-Stereocenters by Asymmetric Allylation of Resorcinol Boronates: Application to the Synthesis of Merocyclophane A

Abstract

Installing multiple noncontiguous stereocenters in a single catalytic event offers a powerful platform for constructing complex three-dimensional molecular architectures, yet asymmetric methodologies capable of selectively forging remote 1,n-stereochemical relationships remain limited. Here we disclose a strategy for the simultaneous installation of 1,6-stereocenters via para-selective activation of chiral resorcinol boronates with π-allyl iridium complexes. Upon oxidation-induced rearomatization, the resulting dearomatized intermediates furnish the allylated products in an overall transformation that exhibits excellent regio- and stereoselectivity. Crucially, independent variation of the ligand and boronic ester configuration provides predictable access to all four stereoisomers with no observable match–mismatch effects. The synthetic potential of the methodology is exemplified by a concise total synthesis of the cyanobacteria-derived [7.7]paracyclophane merocyclophane A, in which all stereocenters are installed simultaneously on the resorcinol core in a single step.