Origin of Stereoselectivity of the Alkylation of Cyclohexadienone-Derived Bicyclic Malonates

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• 作者：Kelly A. Volp ; Andrew M. Harned
• 刊名：The Journal of Organic Chemistry
• 出版年：2013
• 出版时间：August 2, 2013
• 年：2013
• 卷：78
• 期：15
• 页码：7554-7564
• 全文大小：505K
• 年卷期：v.78,no.15(August 2, 2013)
• ISSN：1520-6904

文摘

The diastereoselectivity of the alkylation of bicyclic malonates has been studied experimentally and computationally. In accordance with previous observations during a total synthesis of sorbicillactone A, alkylations involving methyl iodide proceed from the concave (endo) face of the bicyclo[4.3.0]nonene ring system. In contrast, carbon-based electrophiles larger than methyl iodide approach from the convex (exo) face. Computational studies using M06-2X and B3LYP methods have revealed that the observed stereoselectivity is explained by subtle energetic differences between a staggered transition state with less torsional strain and unfavorable steric interactions with the cyclohexenone ring. Using this model as a guide, hydrogenation of the C鈥揅 double bond was used to alter the steric environment of the substrate. As expected, this led to a reversal in the diastereoselectivity during the alkylation with methyl iodide.