Influence of Amino Acid Stereocenters on the Formation of Bicyclic N,O-Acetals
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- 作者：Gonzalo Jim茅nez-Os茅s ; Carlos Aydillo ; Jes煤s H. Busto ; Mar铆a M. Zurbano ; Jes煤s M. Peregrina ; Alberto Avenoza
- 刊名：Journal of Organic Chemistry
- 出版年：2014
- 出版时间：March 21, 2014
- 年：2014
- 卷：79
- 期：6
- 页码：2556-2563
- 全文大小：414K
- 年卷期：v.79,no.6(March 21, 2014)
- ISSN：1520-6904
文摘
In recent years, our group has reported the highly diastereoselective acid-catalyzed N,O-acetalization/intramolecular transcarbamoylation cascade of reactions between protected 伪-amino acid derivatives (Ser and Thr) and tetramethoxyalkanes. The resulting oligocyclic N,O-acetals have been used as excellent chiral building blocks for asymmetric transformations such as diastereoselective alkylation of the 伪-position. We now evaluate the scope of the reaction with related non-natural 伪-amino acid derivatives. A combined experimental and theoretical study reveals the key influence of the 伪-carbon substitution (serine versus 伪-methylserine) and the relative configuration of 伪-/尾-carbons (threonine versus allo-threonine) in the thermodynamic stability of the products and, as a consequence, the stereochemical outcome of the reaction. Notably, the complete diastereoselectivity achieved with natural amino acid precursors is completely lost with their non-natural analogues.