Synthesis,alkali metal picrate extraction,and alkali metal cation binding selectivities of some new cage‐annulated polyoxamacrocyclic crown ethers

Five new cage‐annulated crown ethers, i.e., 4a, 4b, 6b, 11a, and 11b, have been synthesized and their respective alkali metal picrate extraction profiles along with that of a previously synthesized host molecule, 6a, have been obtained. These results are compared with the corresponding results obtained for electrospray ionization mass spectrometric (ESI‐MS) measurements of relative binding selectivities displayed by the same hosts toward a series of alkali metal chlorides. Among the crown‐5 hosts studied, 6a displays enhanced avidity toward complexation with K⁺ picrate in liquid‐liquid extraction experiments. Among the three crown‐6 hosts, 4b proved to be the best alkali metal picrate extractant and displayed significant levels of avidity toward complexation with the larger alkali metal cations (i.e., K⁺, Rb⁺, and Cs⁺). The trends in the picrate extraction and the ESI‐MS results obtained herein show several notable similarities and some differences. The similarities generally stem from size‐selective binding properties that are intrinsic to the different cavity sizes of the cage‐annulated macrocycles, whereas the differences reflect the important influence of solvation effects on the binding properties of the macrocycles.     

Stereoelectronic Control of Additions of Vinylmagnesium Bromide to 1-Methyland 3-Methylpentacyclo[5.4.0.02,6.03,10.05.9]undecane-8,11-diones and to 1-Methylhexacyclo[10.2.1.0.02,11.04,9.04,14.09,13]pentadeca-5,7-diene-3,10-dione

Grignard addition of excess vinylmagnesium bromide to 1-methyland 3-methylpentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane-8,11-diones (1a and 1b, respectively) and to 1-methylhexacyclo[10.2.1.0^2,11.0^4,9.0^4,14.0^9,13]pentadeca-5,7-diene-3,10-dione (4) each proceed regiospecifically to afford a single hemiketal adduct (i.e., 2a, 3a, and 5a, respectively). The structure of each of the three reaction products was established unequivocally via application of X-ray crystallographic methods. Relative energies for the model transition states obtained from geometry optimizations at the Hartree–Fock level of theory in basis set 3-21G(d) indicate that these reactions are kinetically controlled.     

Complete NMR elucidation of a novel trishomocubane hydantoin and its mono- and bis-t-Boc protected derivatives

The syntheses of a novel trishomocubane hydantoin and its mono- and bis-protected t-Boc derivatives are described. The less nucleophilic N-3' nitrogen of the hydantoin ring is protected first when treated with di-tert-butyl dicarbonate (t-Boc anhydride), possibly owing to steric hindrance by the bulky trishomocubane cage skeleton. More basic conditions were required to form the bis-protected t-Boc hydantoin with the same reagent. The structures of these novel compounds were elucidated with 2D NMR techniques. The proton spectrum of the trishomocubane skeleton is complex owing to major overlap of proton signals. A high-level DFT calculation was used to determine some of the crucial interatomic positions, which assisted with the elucidation of the structures. The assignment of proton and carbon signals of the three structures is described and it differs significantly from each other and also from the trishomocubanol precursor. The bis-Boc hydantoin is required for a more facile hydrolysis to the corresponding trishomocubane amino acid at room temperature.     

Synthesis of novel cage oxaheterocycles

m-CPBA-promoted Baeyer-Villiger oxidation of pentacyclo[6.3.0.0(2,6).0(3,10).0(5,9)]undecan-4-one (1) afforded the corresponding lactone 2 in 93% yield. Lithium aluminum hydride promoted reduction of lactones 2, 6, and 9, performed in the presence of BF(3).OEt(2) reagent, afforded the corresponding cage ethers, i.e., 4, 7, and 10, respectively. Two methods that can be used to replace a cage C=O group by ether oxygen without concomitant rearrangement are delineated. A key step in the first of these methods employs m-CPBA promoted "double Criegee rearrangement", which was used to convert pentacyclo[6.3.0.0(2,6).0(3,10).0(5,9)]undecan-4-one diethyl acetal (11) into 7,9-dioxapentacyclo-[8.3.0.0(2,6).0(3,12).0(5,11)]tridecan-8-one (12). Subsequently, 12 was converted into 4-oxapentacyclo[6.3.0.0(2,6).0(3,10).0(5,9)]undecane (14) via a two-step reduction-dehydration reaction sequence. The second method utilized PhI(OAc)(2)-I(2) reagent to convert cage lactols 15 and 17 into the corresponding cage ethers, i.e., 14 and 2-oxaadamantane (18), respectively.