Hebert Sebastien P, Cha Jin K, Brash Alan R, Schlegel H Bernhard
Department of Chemistry, Wayne State University, Detroit, Michigan 48202, USA.
Org Biomol Chem. 2016 Apr 14;14(14):3544-57. doi: 10.1039/c6ob00204h. Epub 2016 Mar 15.
The cyclopentane core is ubiquitous among a large number of biologically relevant natural products. Cyclopentenones have been shown to be versatile intermediates for the stereoselective preparation of highly substituted cyclopentane derivatives. Allene oxides are oxygenated fatty acids which are involved in the pathways of cyclopentenone biosynthesis in plants and marine invertebrates; however, their cyclization behavior is not well understood. Recent work by Brash and co-workers (J. Biol. Chem., 2013, 288, 20797) revealed an unusual cyclization property of the 9(S)-HPODE-derived allene oxides: the previously unreported 10Z-isomer cyclizes to a cis-dialkylcyclopentenone in hexane/isopropyl alcohol (100 : 3, v/v), but the known 10E-isomer does not yield cis-cyclopentenone under the same conditions. The mechanism for cyclization has been investigated for unsubstituted and methyl substituted vinyl allene oxide using a variety of methods including CASSCF, ωB97xD, and CCSD(T) and basis sets up to cc-pVTZ. The lowest energy pathway proceeds via homolytic cleavage of the epoxide ring, formation of an oxyallyl diradical, which closes readily to a cyclopropanone intermediate. The cyclopropanone opens to the requisite oxyallyl which closes to the experimentally observed product, cis-cyclopentenone. The calculations show that the open shell, diradical pathway is lower in energy than the closed shell reactions of allene oxide to cyclopropanone, and cyclopropanone to cyclopentenone.
环戊烷核心结构在大量具有生物学相关性的天然产物中普遍存在。环戊烯酮已被证明是用于立体选择性制备高度取代的环戊烷衍生物的通用中间体。丙二烯氧化物是含氧脂肪酸，参与植物和海洋无脊椎动物中环戊烯酮生物合成途径；然而，它们的环化行为尚未得到很好的理解。布拉什及其同事最近的研究工作（《生物化学杂志》，2013年，第288卷，第20797页）揭示了9(S)-HPODE衍生的丙二烯氧化物的一种不寻常的环化性质：先前未报道的10Z-异构体在己烷/异丙醇（100∶3，v/v）中环化生成顺式二烷基环戊烯酮，但已知的10E-异构体在相同条件下不会生成顺式环戊烯酮。使用包括CASSCF、ωB97xD和CCSD(T)以及高达cc-pVTZ的基组等多种方法，对未取代和甲基取代的乙烯基丙二烯氧化物的环化机理进行了研究。能量最低的途径是通过环氧环的均裂，形成氧烯丙基双自由基，其很容易闭环生成环丙酮中间体。环丙酮开环生成所需的氧烯丙基，后者闭环生成实验观察到的产物顺式环戊烯酮。计算结果表明，开壳层双自由基途径的能量低于丙二烯氧化物生成环丙酮以及环丙酮生成环戊烯酮的闭壳层反应。
