Photochemical Transformations of Proteinogenic and Non-Proteinogenic Amino Acids

The photochemistry of N-activated enantiomerically pure α-amino acids is described with emphasis on chemo-, regio-, stereo-, and spin selectivity. An especially valuable chromophore is the phthalimido group. The first excited singlet states are short-lived and deactivated (chemically) via homolytic CH cleavage or (physically) via electron-transfer steps. The first excited triplet states are chemically deactivated via electron-transfer reactions and subsequent deprotonation/coupling steps. A wide variety of product types were synthesized, and potential target molecules were available by tuning the reaction conditions. Also remote groups can be activated by means of electron-transfer steps, which represents an attractive new synthetic protocol for macrocyclization

Microphotochemistry - a new resources efficient synthesis tool approach

Microphotochemistry, i.e. photochemistry in microstructured reactors, is a novel research area of the 21st century. It combines established techniques in organic photochemistry and continuous flow microsystem engineering with advances in light technology. This research work aimed to develop a novel resource- and energy-efficient approach in synthetic chemistry and to demonstrate that microflow-photochemistry can serve as a compact, rapid and resource efficient R&D tool. A series of homogeneous and heterogeneous photoreactions have been studied in microreactors to evaluate the potential of microphotochemistry. A range of acetonesensitized photodecarboxylation reactions involving phthalimides was investigated in commercially available microreactor dwell device and a number of isopropanol additions to furanones were studied in newly designed within the project LED-driven microchip. All results were compared to analogous experiments in conventional Rayonet reactor. In all cases examined, the reactions performed in the chosen microreactors gave higher conversions or yields. This finding was explained by the generated data of light penetration, irradiated surface-to-volume ratio, energy efficiency and space-time yield. The numbers achieved for continuous flow systems were notably higher compared to the conventional setup. This finding nicely proved superiority of microphotochemistry concept. Another commercially available device falling film microreactor was successfully adapted for the photooxygenation of -terpinene and new safer methodology have been developed for the synthesis of potentially explosive endoperoxide ascaridole. Major disadvantages of commercially available microreactors are, however, the fixed length of the reaction channel and the single-channel design. Although numbering-up can be achieved using an array of microreactors, which required significant costs investment. Flexible PTFE capillaries represent a cost-efficient alternative. Thus a simple continuous microflow dual-capillary reactor and its optimised version multimicrocapillary tower were developed. The tower design enables parallel operation of 10 experiments and it was successfully tested for reaction optimization, library synthesis and scale-up. The multi-capillary design may be easily transferred to other microflow applications such as parallel testing of biologically active compounds, process modeling, in situ analysis and combinatorial chemistry. Consequently, micro-photochemistry may serve as a compact, rapid and resource efficient R&D tool and opens new approaches for synthetic chemistry

Synthetic potential of the PET-decarboxylation of ω-phthalimido carboxylic acids

Photodecarboxylation of potassium salts of w-phthalimido alkanoates in water/acetone mixtures was used to synthesize medium- and large-ring compounds. An efficient synthesis of a benzopyrrolizidine from the corresponding glutamic monomethyl ester was developed. This product was transformed into functionalized pyrrolizidines 3 and 4 with high diastereoselectivity using acyliminium chemistry. Macrocyclic lactones 6, 9a were accessible from their acyclic precursors by the same procedure in high yields. A subsequent photoextrusion of carbon dioxide leading to spirocyclopropanes 11 was discovered in the case of the photolabile seven- and eight-membered macrolides 10a and 10b

Multicomponent/Palladium-Catalyzed Cascade Entry to Benzopyrrolizidine Derivatives: Synthesis and Antioxidant Evaluation

A versatile and efficient protocol for the synthesis of highly substituted benzopyrrolizidines (tetrahydro-3<i>H</i>-pyrrolo­[2,1-<i>a</i>]­isoindol-3-ones) is reported. The strategy consisted of an Ugi four-component reaction/elimination methodology to afford dehydroalanines containing <i>trans-</i>cinnamic acid derivatives and different substituted 2-bromobenzylamines, followed by a palladium-catalyzed 5-exo-trig/5-exo-trig cascade carbocyclization process. Gratifyingly, benzopyrrolizidines were obtained in moderate to good yields (42–77%) with a <i>Z</i> geometry due to the structural requirements for <i>syn</i>-β-hydride elimination. The prepared heterocyclic scaffolds are decorated with several substituents and incorporate a benzopyrrolizidine-fused system, along with an embedded cinnamic acid derivative, two privileged medicinal chemistry scaffolds. Additionally, since some of the compounds are derived from the well-known antioxidants ferulic and sinapinic acids, they were tested for their in vitro antioxidant capacity. The data suggested that compounds having a <i>p-</i>hydroxyl group showed moderate 2,2-diphenyl-1-picrylhydrazyl-radical-scavenging activity and were effective antioxidants in preventing lipoperoxidation in a thiobarbituric acid reactive substances assay

One-Pot Protocol to Functionalized Benzopyrrolizidine Catalyzed Successively by Rh₂(OAc)₄ and Cu(OTf)₂: A Transition Metal–Lewis Acid Catalysis Relay

4-<i>N</i>-Allylarylpropylamino-1-sulfonyl triazoles are converted to structurally unique benzopyrrolizidinyl sulfonamides in a one-pot operation. Intramolecular capture of rhodium carbene with arylamino nitrogen gives rise to the formation of an ammonium ylide immediate. A [2,3]- or [1,2]-rearrangement occurs to give a 2-allylpyrrolidinyl-2-carbimine intermediate which undergoes Cu­(OTf)₂ catalyzed aza-Friedel–Crafts cyclization to finish a highly functionalized tricyclic system decorated with a synthetically difficult quaternary carbon center, a sulfonamide group, and an allyl segment