Multistereocenter-Containing Cyclopentanoids from Ynamides via Oxazolidinone-Controlled Nazarov Cyclization

Achieving ready-enantioselective access to multistereocenter-containing cyclopentyl rings is an area of great significance to organic synthesis. In this work, we describe a general protocol for accessing multistereocenter-containing cyclopentanoids from simple <i>N</i>-alkynyloxazolidinones (<b>Ox</b>-ynamides). This protocol involves conversion of <b>Ox</b>-ynamides into <b>Ox</b>-activated divinyl and aryl vinyl ketones that undergo facile Nazarov cyclization with excellent chemo-, regio-, and stereocontrol. The <b>Ox</b> auxiliary directs all aspects of reactivity and selectivity, both in the electrocyclization and in the subsequent transformations of the resulting oxyallyl intermediate. Stereoinduction in the electrocyclization results from a “coupled-torque” mechanism in which rotation of the <b>Ox</b> group, driven by increasing orbital overlap of the nitrogen lone pair with the incipient oxyallyl cation, is coupled with the rotation of the termini of the pentadienyl cation, favoring a particular direction of conrotatory ring closure (torquoselectivity). The associated lone-pair stabilization of the transition state by <b>Ox</b> promotes cyclization of traditionally resistant substrates, broadening the scope of this asymmetric Nazarov cyclization. The <b>Ox</b> group also facilitates the stereo- and regioselective incorporation of nucleophiles (Nu) and dienes, giving more complex, multistereocenter containing cyclopentanoids. Finally, the <b>Ox</b> group is readily removed and recovered or can be converted into other amine functionalities