Patel Ashay, West F G, Houk K N
Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
J Org Chem. 2015 Mar 6;80(5):2790-5. doi: 10.1021/acs.joc.5b00070. Epub 2015 Feb 24.
The 6π electrocyclizations and Nazarov cyclizations of a series of bridged bicyclic substrates were modeled with the M06-2X density functional and the def2-TZVPP basis set, and the factors responsible for the reactivities of these substrates and the stereoselectivities of their ring closures were identified. The ring closures of these bridged bicyclic trienes are up to a million-fold faster (ΔΔG(⧧) = 10 kcal mol(-1)) than that of 1,3,5-hexatriene, despite the absence of any activating functional groups. Three effects, preorganization, predistortion, and a CH π interaction, are responsible for this sizable difference in reactivity. Stereoselectivity is partially controlled by torsional effects, but for highly exo selective electrocyclizations, it is reinforced by a second effect (either a CH π interaction or a steric clash). The absence of this second effect in the ring closures of several divinyl ketones explains the reduced selectivity of these ring closures. In one case, a divinyl ketone (ketone 6) undergoes Nazarov cyclization to yield the endo product preferentially. For this example, through-space interaction of a nonconjugated alkene with the divinyl ketone π system in the endo transition state and a steric effect override the intrinsic exo selectivity.
使用M06-2X密度泛函和def2-TZVPP基组对一系列桥连双环底物的6π电环化反应和纳扎罗夫环化反应进行了建模，并确定了影响这些底物反应活性及其环化立体选择性的因素。尽管没有任何活化官能团，但这些桥连双环三烯的环化反应比1,3,5-己三烯的环化反应快达一百万倍（ΔΔG(⧧) = 10 kcal mol(-1)）。预组织、预畸变和CH π相互作用这三种效应导致了这种显著的反应活性差异。立体选择性部分受扭转效应控制，但对于高度外式选择性的电环化反应，它会因第二种效应（CH π相互作用或空间位阻冲突）而增强。几种二乙烯基酮环化反应中不存在这种第二种效应，这解释了这些环化反应选择性降低的原因。在一个例子中，一种二乙烯基酮（酮6）优先发生纳扎罗夫环化反应生成内式产物。对于这个例子，在endo过渡态中，非共轭烯烃与二乙烯基酮π体系的空间相互作用和空间位阻效应超过了固有的外式选择性。
