Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• alkyl chain. Substrates with p-tolylsulfonyl (Ts), p-nitrobenzenesulfonyl (Ns) and benzenesulfonyl (Bs) protecting groups were cyclised in high yields to the corresponding 3-fluoropyrrolidine derivatives 14. A range of unsaturated amines were successfully cyclised. However, substrates with substituents

• = protecting group. Synthesis of β-fluorinated piperidines. Intramolecular fluoroaminations of unsaturated amines published by Li. Intramolecular aminofluorination of unsaturated amines using 1-fluoro-3,3-dimethylbenziodoxole (12). PG = protecting group. 3-fluoropyrrolidine synthesis. aDiastereomeric ratio

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• crystallographic data using the 3-fluoropyrrolidinium cation and 3-fluoropyrrolidine. Subsequently, we explored the relative energy of all favored conformations of all different stereoisomers of 2,3-, 2,4-, and 3,4-difluoropyrrolidines at the B3LYP-D3BJ/6-311++G** level. A generalized anomeric effect, arising from

• Lewis interactions from a natural bond orbital perspective. Keywords: anomeric effect; fluoropyrrolidine; gauche effect; stereochemistry; Introduction The pyrrolidine ring structure is prevalent in numerous natural alkaloids and is an important feature of the proline and hydroxyproline residues that

• interactions [4]. Protonation of 3-fluoropyrrolidine generates the 3-fluoropyrrolidinium cation, and this typically results in a highly favored conformation in both the gas phase and solution where the fluorine and nitrogen atoms are cis, mirroring the behavior observed in analagous 4- and 6-membered ring

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• crystallization. Finally, the study revealed a few polar interactions of the fluoropyrrolidine ring within the protein microenvironment. In a study on thioredoxin, four out of five proline residues were mutated to alanine, and the only remaining proline residue was the one adopting a cis-amide-bond conformation

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• , GlaxoSmithKline disclosed a route to a fluoropyrrolidine 6 using a Wittig reaction between phosphonium salt 4 and aldehyde 5 [2]. The synthesis of phosphonium salt 4 (itself requiring 6 steps including partial saturation of a 1,8-naphthyridine moiety) and the formation of the triphenylphosphine oxide byproduct in

• was unsuccessful as complete racemisation was observed, with olefination requiring five days to complete. No olefination was seen using DIPEA under refluxing conditions. As such, this sequence, as currently performed, is suitable for substrates lacking an acidic α-proton (fluoropyrrolidine core 6) or

• integrin inhibitors. Commonly used synthetic routes to tetrahydro-1,8-naphthyridine moieties by hydrogenation of saturated naphthyridines 3. Previous synthetic route to fluoropyrrolidine 6 utilising a Wittig reaction and the novel, higher yielding route using a Horner–Wadsworth–Emmons reaction. Synthesis