Visible light-activated reactions continue to expand and diversify. The example shown here is a Birch reduction achieved by organophotoredox reagents.

RESULTS AND DISCUSSIONThe first stage of the synthesis of the -pyridyl -amino acids involved the preparation of suitably protected enone-derived -amino acids (Scheme 1). Initially, N-trityl protected phosphonate ester 3 was prepared in three-steps (92% overall yield) from L-aspartic acid 1. 13 Following protection of the amino and carboxylic acid groups, the key step involved the highly regioselective reaction of the anion of dimethyl methylphosphonate with the sterically accessible -methyl ester of 2 to give phosphonate ester 3. Horner-Wadsworth-Emmons reaction of 3 with a wide range of aldehydes under mild conditions, gave enones 4a-j, exclusively as the E-isomers. 14,15 The focus of this project was to prepare aryl substituted pyridyl side-chains and therefore, benzaldehyde derivatives were mainly used to explore the scope of this reaction. As expected, the majority of these gave high yields of the E-enones (66-95%), although highly electron-rich aldehydes required longer reaction times (120 h) and gave more modest yields (e.g. 4e). Scheme 1. Synthesis of Enone-Derived -Amino Acids 4a-j a a Isolated yields are shown. peptide synthesizer using Rink Amide ChemMatrix® resin as the polymer support 22 and routine SPPS methodology (Scheme 3). On coupling Fmoc-L-Lys(Boc)-OH onto the polymer support using HCTU activation, successive rounds of piperidine-mediated N-deprotection and coupling using the next amino acid gave the pentapeptide. Following a subsequent N-terminal Fmoc-deprotection, the Fmoc-protected version of -pyridyl -amino acid 8d, compound 9 was coupled onto the polymer-supported pentapeptide. 23 After a final Fmoc-deprotection step, the N-terminus was acetyl capped and a TFA cleavage cocktail that included triisopropylsilane (TIPS) as a cation scavenger was used to remove the side-chain protecting groups and release the peptide from the polymer support. The resulting hexapeptide, 10 was purified by reverse phase-HPLC (>95% purity) and characterized by high-resolution electrospray ionization mass spectrometry (see Supporting Information for data). Scheme 3. SPPS of a -Pyridyl -Amino Acid Containing HexapeptideAs the -amino acids contained -deficient pyridine moieties, it was proposed that electron-rich conjugating groups may confer fluorescent properties through a charge-transfer (push-pull) mechanism. 24 Accordingly, the optical properties of -pyridyl -amino acids 8a-l were measured. As expected, pyridines with non-conjugating or electron-deficient substituents showed weak fluorescence, while compounds with electron-rich substituents showed strong fluorescence (Figure 2b and Table 1). In

Conformationally rigid unnatural α-amino acids bearing a pyrazoloquinazoline ring system that are amenable to both one- and two-photon excitation have been developed as new fluorescent probes.

The synthesis of a new class of benzotriazole-derived α-amino acid is described using a highly efficient nucleophilic aromatic substitution of ortho-fluoronitrobenzenes with l-3-aminoalanine and a polymer-supported nitrite reagent-mediated diazotization and cyclization of the subsequent 1,2-aryldiamines as the key steps. Further functionalization of the benzotriazole unit by preparation of halogenated analogues and Suzuki–Miyaura cross-coupling with aryl boronic acids allowed the synthesis of α-amino acids with conjugated side chains. Analysis of the photophysical properties of these α-amino acids revealed that incorporation of electron-rich substituents results in charge-transfer-based, fluorescent compounds with MegaStokes shifts.