Organic reactions in the solid state: Reactions of enclathrated 3,4- epoxycyclopentanone (= 6-oxobicyclo[3.1.0]hexan-3-one) in Tri-othymotide and absolute configuration of 4-hydroxy- and 4-chlorocyclopent-2-en-1-one

Article abstract of DOI:10.1002/(SICI)1522-2675(19990310)82:3<418::AID-HLCA418>3.0.CO;2-D

Several aspects of the heterogeneous actions of aqueous and gaseous HCl on the chemical behavior of 3,4-epoxycyclopentanone (=6- oxablcyclo[3.1.0]hexan-3-one; 1) included in the asymmetric cages of tri-o- thymotide (TOT) clathrates belonging to space groups P3₁21 are described, showing specific features strikingly at variance with those observed in liquid solutions. In a first step, the substrate underwent an acid-promoted allylic isomerization, as already observed in our previous investigations, to give optically active 4-hydroxycydopent-2-en-1-one (2). In a Consecutive step, a displacement of the OH group was accomplished by the Cl^- anion to afford the corresponding chloro compound 3. Polymorphism was encountered in the preparation of TOT/1 clathrates. Recrystallization of TOT in the pure guest 1 yielded micro-twinned crystals belonging to the P3₁ space group (host/guest ratio 1: 1), whereas the expected P3₁21 lattice grew from a mixture of TOT, 1 and MeOH. The structural determination of TOT/1 was carried out by X-ray diffraction (Fig. 1). Kinetic measurements were achieved that shed light on some striking features of this type of heterogeneous reactions for solid-liquid and solid-gas systems. Several reactions of pure clathrate antipodes (+)-TOT/1 with gaseous HCl were carried out under various conditions; concentration and enantiomer-excess(ee) determinations of the products 2 and 3 allowed to establish a larger ee for 3, thus demonstrating the influence of the host-guest diastereomeric association on the progression of the reaction. The correlation of optical activities of the host and products for the global reaction disclosed the sequence (+)-(M)-TOT/1 → (- )-2 → (-)-3. A new way for the preparation of 2 was devised. It was further demonstrated that the X-ray structure analysis of the chiral clathrate (M)- TOT/(+)-2 (Fig. 4) associated with chitoptical measurements was an efficient and straightforward method to determine the absolute (+)-(R)-configuration of the guest. The enantioselectivity of the TOT clathrate for 2 was established by two different methods which allowed the appraisal of an accurate revised value of the specific rotation of 2. The enclathration of 3 occurred exclusively in the orthorhombic centrosymmetric host lattice Pbca, thus prohibiting the X-ray structural determination of the guest absolute configuration. The problem of finding a pathway to the intended enantiomer enrichment of 3 was worked out through the action of aqueous HCI on microcrystalline (+)-TOT/(-)-(S)-2 that gave an optically active mixture of unreacted 2 with 3 as sole product. The pure optically active 3 was isolated by Subsequent TLC. The resolution of 3 was achieved by GC over a chiral column and its (unknown) specific rotation measured. The absolute configuration of 3 was established by the measurement of the enantiomer purity of the optically active mixture 3 obtained after the total conversion of (-)-(S)-2 in the presence of thionyl chloride in Et₂O, dioxane, and benzene. It was deduced that the (-)-3 enantiomer had the (S)-configuration.