Synthesis of Medium- and Large-Ring Compounds Initiated by Photochemical Decarboxylation of ω-Phthalimidoalkanoates

The synthesis of a variety of hydroxylactams from ω-phthalimidoalkanoates using a triplet-sensitized photodecarboxylation reaction initiated by intramolecular photo electron transfer is described. Ring sizes available by this method span from 4 (benzazepine-1,5-dione 7 ) to 26 (cyclodipeptide 26e ). Ground-state template formation is proposed as the explanation for the high efficiency of this reaction and for the decrease in reactivity in the presence of organic bases instead of metal carbonates. The crucial step in this macrocyclization reaction seems to be the protonation of the intermediary ketyl radials (Scheme 4). Spacer groups investigated were alkyl chains (C₃-C₁₁: 5c-h, 11a, 12 ), ether ( 16, 18 ), ester ( 20, 22 ), and amide ( 26a-f ) linkages. Within the detection limits, no dimeric (= decarboxylative coupling) products were observed, indicating the high preference for intra-vs. intermolecular photoelectron transfer. The C,C radical combination step proceeds with low stereoselectivity (cf, products 11 and 12 ) in contrast to comparable singlet reactions. Except for the lactones 22 , all products were stable under the photolysis conditions. Prolonged irradiation of 22 led to the formation of the spiro compounds 23 , probably via an intermediary acyliminium betaine (Scheme 8). One serious limitation of the decarboxylative macrocyclization is its incompatibility with the glycine spacer (as in 27a and 27b ), probably the consequence of a strong intramolecular H-bond (Scheme 10).     

Alpha-Carbonic Acid Revisited: Carbonic Acid Monomethyl Ester as a Solid and its Conformational Isomerism in the Gas Phase

In this work, earlier studies reporting α-H₂CO₃ are revised. The cryo-technique pioneered by Hage, Hallbrucker, and Mayer (HHM) is adapted to supposedly prepare carbonic acid from KHCO₃. In methanolic solution, methylation of the salt is found, which upon acidification transforms to the monomethyl ester of carbonic acid (CAME, HO-CO-OCH₃). Infrared spectroscopy data both of the solid at 210 K and of the evaporated molecules trapped and isolated in argon matrix at 10 K are presented. The interpretation of the observed bands on the basis of carbonic acid [as suggested originally by HHM in their publications from 1993–1997 and taken over by Winkel et al., J. Am. Chem. Soc. 2007 and Bernard et al., Angew. Chem. Int. Ed. 2011] is inferior compared with the interpretation on the basis of CAME. The assignment relies on isotope substitution experiments, including deuteration of the OH- and CH₃- groups as well as ¹²C and ¹³C isotope exchange and on variation of the solvents in both preparation steps. The interpretation of the single molecule spectroscopy experiments is aided by a comprehensive calculation of high-level ab initio frequencies for gas-phase molecules and clusters in the harmonic approximation. This analysis provides evidence for the existence of not only single CAME molecules but also CAME dimers and water complexes in the argon matrix. Furthermore, different conformational CAME isomers are identified, where conformational isomerism is triggered in experiments through UV irradiation. In contrast to earlier studies, this analysis allows explanation of almost every single band of the complex spectra in the range between 4000 and 600 cm⁻¹.     

Synthesis and antitrypanosomal activity of 2-aminomethyl-1-(2-oxyphenyl)naphthalenes

A broad variety of enantiopure axially chiral 2-aminomethyl-1-(2-oxyphenyl)naphthalenes were prepared via short and efficient synthetic pathways by using the ‘lactone method’ for the regio- and stereoselective construction of the biaryl axis. Their in vitro activity against Trypanosoma cruzi, the causative agent of Chagas' disease, was evaluated. In particular, the M-configured atropisomers, with the 2-oxy function equipped with an O-triflate group, were found to exhibit good antitrypanosomal activities (down to IC₅₀=1.6 μg/mL), combined with low levels of cytotoxicity.     

In situ probing of fast defect annealing in Cu and Ni with a high-intensity positron beam

A high-intensity positron beam is used for specific in?situ monitoring of thermally activated fast defect annealing in Cu and Ni on a time scale of minutes. The atomistic technique of positron-electron annihilation is combined with macroscopic high-precision length-change measurements under the same thermal conditions. The combination of these two methods as demonstrated in this case study allows for a detailed analysis of multistage defect annealing in solids distinguishing vacancies, dislocations, and grain growth.