title: Experimental and theoretical studies on the Nazarov cyclization/Wagner-Meerwein rearrangement sequence.
abstract: Highly functionalized cyclopentenones can be generated by a chemoselective copper(II)-mediated Nazarov/Wagner-Meerwein rearrangement sequence of divinyl ketones. A detailed investigation of this sequence is described including a study of substrate scope and limitations. After the initial 4π electrocyclization, this reaction proceeds via two different sequential [1,2]-shifts, with selectivity that depends upon either migratory ability or the steric bulkiness of the substituents at C1 and C5. This methodology allows the creation of vicinal stereogenic centers, including adjacent quaternary centers. This sequence can also be achieved by using a catalytic amount of copper(II) in combination with NaBAr(4)(f), a weak Lewis acid. During the study of the scope of the reaction, a partial or complete E/Z isomerization of the enone moiety was observed in some cases prior to the cyclization, which resulted in a mixture of diastereomeric products. Use of a Cu(II)-bisoxazoline complex prevented the isomerization, allowing high diastereoselectivity to be obtained in all substrate types. In addition, the reaction sequence was studied by DFT computations at the UB3LYP/6-31G(d,p) level, which are consistent with the proposed sequences observed, including E/Z isomerizations and chemoselective Wagner-Meerwein shifts.
authors.affiliation: Department of Chemistry, University of Rochester, Rochester, New York 14627, USA.
authors.forename: David
authors.initials: D
authors.lastname: Lebœuf
authors.forename: Vincent
authors.initials: V
authors.lastname: Gandon
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ciesielski
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Frontier
mesh_terms: D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D004563:Electrochemistry / Q000379:methods*; D004583:Electrons; D007659:Ketones / Q000737:chemistry; D058116:Lewis Acids / Q000737:chemistry; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D007659:Ketones; D058116:Lewis Acids; D008024:Ligands; D003300:Copper