Skeletal Editing through Cycloaddition and Subsequent Cycloreversion Reactions

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

ConspectusSkeletal editing, which involves adding, deleting, or substituting single multiple atoms within ring systems, has emerged as a transformative approach in modern synthetic chemistry. This innovative strategy addresses the ever-present demand for developing new drugs and advanced materials by enabling precise modifications of molecular frameworks without disrupting essential functional complexities. Ideally performed at late stages synthesis, skeletal editing minimizes need cost- labor-intensive processes often associated with de novo thus accelerating discovery optimization complex architectures. While current efforts predominantly focus on monatomic-scale modifications, molecules through cycloaddition followed cycloreversion offers unique to manipulate double-atomic scale. introduces possibilities chemical transformations enables such double-atom transmutation, formal single-atom atom insertion. Early examples relied inherent high reactivity substrates, needed be sufficiently active undergo possess good leaving groups subsequent fragmentation (cycloreversion) step. Recently, however, structural relatively inert substrates become achievable substrate activation strategies designed enhance either step.Along these lines, we recently developed dearomative process activating pyridines. In simple high-yielding operation, oxazinopyridines are readily obtained activated dearomatized isolable intermediates. method enabled us achieve transformation pyridines into benzenes naphthalenes cycloaddition/cycloreversion sequence. this Account, related recent contributions from other research highlighted well, alongside early involving tetrazines, triazines, diazines, similar heterocycles reaction partners. By offering streamlined route modify structures, approaches have demonstrated their ability interconvert arenes heteroarenes shown significant potential late-stage applications well advancing drug synthesis bioactive molecules.In future, will undoubtedly see broader development field editing. New should devised enable not only incorporation nitrogen heteroatoms rings─rather than deletion─but also contraction expand application non-aromatic rings. We hope that advancements summarized Account inspire chemists explore methodologies. pushing boundaries approaches, researchers can unlock opportunities constructing modifying frameworks, eventually paving way chemistry, biology, science.

Language: Английский

Regio- and Stereoselective [3 + 2] cycloaddition of Isatogens with functionalized alkenes and its application to the synthesis of Halichrome a

Tetrahedron Letters, Journal Year: 2025, Volume and Issue: unknown, P. 155626 - 155626

Published: April 1, 2025

Language: Английский