Experimental and Theoretical Studies on the Nazarov Cyclization/Wagner鈥揗eerwein Rearrangement Sequence

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• 作者：David Leb艙uf ; Vincent Gandon ; Jennifer Ciesielski ; Alison J. Frontier
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：April 11, 2012
• 年：2012
• 卷：134
• 期：14
• 页码：6296-6308
• 全文大小：875K
• 年卷期：v.134,no.14(April 11, 2012)
• ISSN：1520-5126

文摘

Highly functionalized cyclopentenones can be generated by a chemoselective copper(II)-mediated Nazarov/Wagner鈥揗eerwein rearrangement sequence of divinyl ketones. A detailed investigation of this sequence is described including a study of substrate scope and limitations. After the initial 4蟺 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 NaBAr₄^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鈥揗eerwein shifts.